tag:blogger.com,1999:blog-40255629240449327022024-03-14T02:02:45.925-07:00Pharmaceutical PolicyBob Bohrerhttp://www.blogger.com/profile/17081349778121412450noreply@blogger.comBlogger57125tag:blogger.com,1999:blog-4025562924044932702.post-91373588928687516872018-08-20T10:31:00.000-07:002018-08-20T10:31:01.657-07:00CAUTION : Phishing Emails with "Subject: Pharmaceutical Policy confirm subscription"<h2 style="text-align: center;">
WARNING</h2>
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Some malicious hacker is sending out bulk emails spoofing my email address as sender with a link to "pharmaceuticalpolicy.info." If you receive such an email delete those emails without clicking any links. I have not and will not send out any emails asking you to confirm your subscription, but I, like anyone with an email address that is displayed on the web, have no way of preventing this kind of misuse. </div>
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Bob Bohrerhttp://www.blogger.com/profile/17081349778121412450noreply@blogger.com0tag:blogger.com,1999:blog-4025562924044932702.post-55962506854666313782018-05-07T20:01:00.000-07:002018-05-07T20:01:59.872-07:00The World of Pharmaceutical Pricing is Changing- Praluent Isn't Just a One-OffThe American Journal Managed Care (AJMC)<a href="http://www.ajmc.com/newsroom/5-things-to-know-about-the-praluentndashexpress-scripts-deal?eKey=&utm_medium=email&utm_campaign=AJMC%20Managed%20Care%20Minute%20-%205-7-18&utm_content=AJMC%20Managed%20Care%20Minute%20-%205-7-18+CID_a313fcfa9db215e66c50fbd5a995393d&utm_source=Campaign%20Monitor&utm_term=5%20Things%20to%20Know%20About%20the%20PraluentExpress%20Scripts%20Deal"> recently published an excellent article</a> about a major pricing for access deal for Regeneron's Praluent, an antibody to PCSK9, which is effective in the treatment of hypercholesteremia in patients who with inadequate response to, or inability to tolerate, statins. In exchange for a DEEP discount in price, Express Scripts has agreed to put Praluent on its National Preferred Formulary List, allowing relatively unhindered access to the drug for the 25 million patients whose insurers use Express Scripts for their formulary management. Readers of this blog know that pharmaceutical companies, like all businesses, charge what the market will bear. This deal reflects a shifting context for "what the market will bear." As the AJMC pointed out, the agreement comes in the wake of an <a href="https://icer-review.org/">ICER</a> (Institute for Clinical Economic Review) <a href="https://jamanetwork.com/journals/jama/article-abstract/2544639">study</a> which validated the clinical benefit of Praluent while pointing to an economic value significantly lower than Regeneron's price for Praluent. The problem with the market for pharmaceuticals has always been the lack of adequate information. While the generation of better information is still costly, the value of that information is becoming overwhelmingly clear. That is why in a world in which both insurers and pharmaceutical companies are under fire for the cost of health care, we will increasingly see studies that provide more of the information the market needs. While in this instance the study resulted in a signifiantly lower price, some costly drugs will indeed prove to be worth their price. I expect both insurers and pharmaceutical companies to increase their funding for such studies. Praluent is not just a one-off, it is a milestone on the road to the future of healthcare.Bob Bohrerhttp://www.blogger.com/profile/17081349778121412450noreply@blogger.com0tag:blogger.com,1999:blog-4025562924044932702.post-87842065246029168292017-10-16T16:12:00.000-07:002017-10-16T16:13:20.975-07:00News on BiosimilarsThere has been quite a bit of interesting pharmaceutical policy news and I hope to post more soon. In the meantime, <a href="http://www.fdanews.com/articles/print/183929-fda-issues-crl-to-mylan-and-biocons-neulasta-biosimilar">here</a> is a news item related to my recent posts on biosimilars. From this story it appears that even the pegylated biologic pegfilgrastim did not present insurmountable difficulties in developing an equally effective, non-immunogenic biosimilar, although the manufacturing issues are still to be resolved.<br />
<br />Bob Bohrerhttp://www.blogger.com/profile/17081349778121412450noreply@blogger.com0tag:blogger.com,1999:blog-4025562924044932702.post-2821315738552474072017-07-28T16:55:00.004-07:002017-07-28T16:55:42.127-07:00Was I Wrong, Or Do We Have A Failure to Communicate?<div class="MsoNormal">
I have been wrong a few times in the sixty-plus years I’ve
been on Earth. Was I wrong about the risk of technical failure in biosimilar
development in my <a href="http://pharmaceuticalpolicy.blogspot.com/2017/06/bio-2017-part-i-virtual-development-is.html">June26th post on virtual biosimilar development?</a> To be clear, what I
mean by technical failure is that the molecule produced and taken through
testing turns out to be non-comparable to the original biologic, either because
it has less effectiveness or greater risks of adverse events, including
immunogenicity.<a href="https://pharmaintelligence.informa.com/resources/product-content/first-cycle-approval-rate"> Therecent news about the 40% “first-cycle” approval rate</a> for the first ten
biosimilar applications reviewed by the FDA caused me to take another look at
the risk of technical failure. I do not believe that the startling low first
cycle approval rate indicates that the technical difficulty of creating a
reasonably good biosimilar is very high, and that the better explanation for
the low initial approval rate may be expressed in one of my very favorite films
of all time, “Cool Hand Luke.” “Captain,” the brutal Warden of the chain gang
prison to which Cool Hand Luke is sentenced, explains the need to punish Luke by
saying “What we’ve got here is a failure to communicate.” While I would never
ever suggest any real similarity or parallel between the FDA and that prison,
it does seem to me that the best explanation for the low first-pass approval
rate for biosimilar applications is indeed a failure to communicate. A closer look
at the six biosimilar applications which received Complete Response Letters
(CRLs) instead of approval helps to clarify the issue. Here is a list of the
biosimilars that received a CRL and the basis for the CRL:<o:p></o:p></div>
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<div class="MsoNormal" style="margin-left: .5in;">
1. Hospira’s Epoetin zeta approval
was delayed by manufacturing concerns. There were no concerns about the actual
molecules safety or efficacy (the drug has been on the market in Europe for
some time).<o:p></o:p></div>
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<div class="MsoNormal" style="margin-left: .5in;">
2. Pfizer’s Epoetin alph was also
delayed because of manufacturing concerns; previous requests for more clinical
data were satisfied. So this molecule also is approvable by the FDA.<o:p></o:p></div>
<div class="MsoNormal" style="margin-left: .5in;">
<br /></div>
<div class="MsoNormal" style="margin-left: .5in;">
There were three different applications
for biosimilars for Pegfilgrastim and all have been delayed.<o:p></o:p></div>
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<br /></div>
<div class="MsoNormal" style="margin-left: .5in;">
3. Coherus’ Pegfilgrastim was
delayed by the FDA’s request for a reanalysis of a subset of samples with a
revised immunogenicity assay and to provide additional manufacturing-related process
information. Clinical data on efficacy and adverse reactions apparently were
apparently satisfactory to the FDA. So although is possible that the revised
immunogenicity assay will disclose some issue with the molecule, it is more
likely that the delays in the Pegfilgrastim biosimilar applications indicate
that the FDA is simply unsure of exactly how to assess immunogenicity for <a href="https://www.ncbi.nlm.nih.gov/pubmed/18778113">pegylated</a> biosimilar
proteins.<o:p></o:p></div>
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4. Apotex’s Pegfilgrastim––Apotex
has not disclosed the concerns raised by the FDA in its CRL.<o:p></o:p></div>
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<br /></div>
<div class="MsoNormal" style="margin-left: .5in;">
5. Sandoz’s Pegfilgrastim––There also
was no disclosure by Sandoz of the concerns expressed by the FDA in its CRL.
However, the data from 3 clinical trials, including two trials for safety and
efficacy in breast cancer patients would seem to demonstrate that the molecule is
safe and effective in treating chemotherapy-induced neutropenia. Here too it
appears that the FDA has additional concerns to be addressed for pegylated
proteins and is still considering how to best resolve those concerns.<o:p></o:p></div>
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<br /></div>
<div class="MsoNormal" style="margin-left: .5in;">
6. Celtrion’s infliximab was approved
in the second cycle after the provision of additional data. This proves that the
molecule was a reasonable and functional biosimilar but that Celtrion and the
FDA had not reached an earlier understanding as to exactly what needed to be
included in the biosimilar application.<o:p></o:p></div>
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There are two conclusions that can be drawn from this limited
data set of the first ten applications. First, manufacturing issues are always
a concern for biologics. Biosimilar manufacturers need to make a good
biosimilar, but they also need to make it in an impeccable facility. Second,
the FDA has concerns about pegylated proteins (such as Pegfilgrastim) that are
still evolving. Manufacturing issues aside, the developers of cytokines and
antibody biosimilars have produced approvable molecules. The 29 biosimilars on
the market in the EU with very few (if any) involuntary withdrawals for safety are
clear evidence of the relative rate technical success. <a href="http://www.quintiles.com/microsites/biosimilars-knowledge-connect">The European experience with biosimilars </a>points to the conclusion that the risk
of technical failure in biosimilar development is low. The early going at the
FDA represents a learning curve in the data collection, submission, and review
process for the biosimilar developers and the FDA. I do not believe I was wrong
about the technical difficulty of creating a biosimilar. What we’ve got here is
a failure to communicate precisely what needs to be done to obtain the FDA’s
approval. <o:p></o:p></div>
Bob Bohrerhttp://www.blogger.com/profile/17081349778121412450noreply@blogger.com0tag:blogger.com,1999:blog-4025562924044932702.post-672148879539425612017-07-07T12:18:00.001-07:002017-07-07T12:18:20.480-07:00FDA Approves Endari for Sickle Cell DiseaseIt should not come as a surprise to readers of this blog- Emmaus Medical <a href="https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm566084.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery">was given FDA approval for it's l-glutamine treatment</a> for sickle cell disease. I posted my analysis of the then-pending application back on June 17th: <a href="https://www.blogger.com/blogger.g?blogID=4025562924044932702#editor/target=post;postID=6618923684215818919;onPublishedMenu=allposts;onClosedMenu=allposts;postNum=6;src=postname">Good News for Sickle-Cell Patients, But How Will Emmaus Make Money? A Look at the Business Side of Pharmaceutical Policy</a>. As I stated then- it will be very interesting to see whether Emmaus is able to successfully complete with other sources of l-glutamine. I look forward to Emmaus' quarterly reports.Bob Bohrerhttp://www.blogger.com/profile/17081349778121412450noreply@blogger.com0tag:blogger.com,1999:blog-4025562924044932702.post-19113982156524244102017-07-04T17:05:00.000-07:002017-07-04T17:05:12.395-07:00BIO 2017: Part II ––Virtual Development Is A Reality<div class="MsoNormal">
In my June 26th post on BIO 2017 I discussed how developing
a biosimilar could now be done by a virtual company, with minimal staff
overseeing the project and contracting with outside vendors for every step in
the process from cell-line development through regulatory approval. The giant
Exhibition Hall for BIO 2017 provided a showcase for a number of vendors who
can perform the necessary parts of the biosimilar development process. I concluded that post by noting that although
a virtual company could oversee all of the development of, for example, a
biosimilar Remicade/infliximab there would certainly be some level of risk in
at least 3 areas. First is the straightforward risk of clinical failure. Clinical
testing of the biosimilar could reveal that the product either is not
comparably effective or is immunogenic, despite pre-clinical analysis of
comparability. There have now been a sufficient number of companies entering
into the development of biosimilars and <a href="http://www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-Europe">a
sufficient number of biosimilars approved in Europe (35 as of June 16, 2017)</a>
for the risk of clinical failure to be at least roughly estimated. A more complete
analysis of companies abandoning particular biosimilar development efforts or
failing to win approval is beyond the scope of this post, but it is now
reasonably clear that while the risk of failure is relatively low. There is some risk of clinical failure but it
is certainly much lower than is the case for new small molecules or pioneer
drugs. The EMA and FDA have responded to very few biosimilars applications
either with an outright rejection of an application or a demand for further
clinical trials.</div>
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<o:p></o:p></div>
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The second risk is the competition risk. With multiple
biosimilars for the same original biologic (as is would be the case for our hypothetical
Remicade biosimilar), selling sufficient quantities of the biosimilar will
require extensive marketing efforts and possibly price discounting to persuade
doctors and payers to prefer our biosimilar over the others. Unlike the risk of
technical failure, the extent of the market risk is both difficult to estimate,
but, in my view, completely manageable. The solution to the market risk for a
virtual company is simply to enter into an agreement with a major buyer at the
very beginning of the effort. For example, under an alternative business model,
the virtual development would undertake procure a supply contract with a major
payer such as United Healthcare, at a pre-agreed deep discount, before
beginning to incur significant development expenses. This approach eliminates
market risk and most marketing expenses.<o:p></o:p></div>
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In addition to the relatively low risk of technical failure
and the manageable market competition risk, there is one more significant risk
to be considered, which is the risk presented by expensive patent infringement
litigation with no certainty concerning the eventual outcome. The current thicket
of large numbers of process patents surrounding most pioneer biologics will
provide far too much fuel for patent litigation and unpredictability to the
process. Although I am generally wary of proposing legislative fixes for
problems, it seems to me that one may be needed here, in the form of an outer
limit on the duration of patent-protection and market exclusivity for the maker
of a reference biologic. One of the most hotly debated provisions of the <a href="https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/ucm216146.pdf">Biosimilar
Competition and Innovation Act</a> (BCPIA) was Section 7(A), which provides a
twelve year of period of exclusivity during which no biosimilar applicant may
be approved simply on the basis of its comparability to the reference, or
pioneer, biologic. Without rehashing that debate, it is interesting to
speculate on at least one likely explanation for that 12-year exclusivity
period: it is remarkably similar to the average period of market exclusivity
that is enjoyed by branded small molecule drugs with reasonably large markets. According
to <a href="https://www.ncbi.nlm.nih.gov/pubmed/27064194">a study by Grabowski,
Long, and Mortimer</a> the average period of market exclusivity for the branded
small-molecule drugs through 2013-2014 was 12.5 years. However, it is
increasingly clear that the BCPIA, with its complex <a href="http://pharmaceuticalpolicy.blogspot.com/2017/06/us-supreme-court-issues-opinion-in.html">“patent
dance” provisions</a>, leaves the development of biosimilars open to
significant risks in the actual infringement litigation. If 12 years is not the
outer limit of market exclusivity, then a slightly longer period, for example
15 years after market entry, certainly is more than long enough for any
biologics reference drug maker to have been rewarded very handsomely for its
pioneering efforts. <a href="http://www.lexology.com/library/detail.aspx?g=1a474762-d1f8-4c91-9c5c-c1a6cc6eb8d3">Amgen
is currently suing Hospira for infringement of process patents</a> that Amgen
holds for the making of erythropoietin, which it markets under the brand name
Epogen. Amgen’s <span style="background: white; color: #333333; font-family: "Roboto Slab","serif"; font-size: 11.5pt; mso-fareast-font-family: "Times New Roman";">Epogen,
its original blockbuster drug, was first approved by the FDA in 1989. Although
some of Epogen’s patents may have been filed under the former system of 17
years from date of issue rather than 20 years from filing, it is close to
stunning that twenty-eight years later Amgen is still seeking to defend its
market exclusivity by claiming patent infringement. While I am certain that my
proposed 15-year limit after market entry on the right to bring infringement
actions against any biosimilar applicant will be debated as too long or too
short, can anyone seriously defend 28 years, or even 20? Virtual biosimilar development
is now possible, and could offer very significant efficiencies and savings. The
technical failure risk and the market competition risk are ordinary business
risks that can be factored into a business plan and dealt with. However, the
risk of costly and uncertain patent infringement litigation for a biosimilar
drug needs more certainty than the BCPIA provides. Fifteen years is enough for
pioneers and would give the healthcare system a real chance at significant and
desperately needed savings.<o:p></o:p></span></div>
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Bob Bohrerhttp://www.blogger.com/profile/17081349778121412450noreply@blogger.com0tag:blogger.com,1999:blog-4025562924044932702.post-60812704323115999832017-06-27T16:34:00.002-07:002017-06-27T16:34:38.940-07:00Much Ado About Little or Nothing
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<span style="color: black; mso-fareast-font-family: "Times New Roman";">The FDA announced its new efforts to "</span><span style="background: white; color: #333333; mso-fareast-font-family: "Times New Roman";"><a href="https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm564725.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery">to
increase competition in the market for prescription drugs</a>" and in my
view it is likely to do little or nothing to affect spending on prescription
drugs in the United States. The first step announced by the FDA is simply that
that the FDA will publish and maintain a list of off-patent branded drugs with
no generics. The second step announced is that the FDA will prioritize review
of ANDAs for generics where there are less than three generics approved for
that drug. The first step is likely to have little impact because it simply
ignores the fact that the major generic companies devote significant resources
to research the patents on the drugs for which they would like to compete,
making the FDA’s effort largely superfluous. The second step is also likely to
do very little. The attractive generic markets draw many entrants while the
less attractive attract far fewer. It is the market size, not the lag in
review, that largely shapes competition in the generic market. No, despite the
periodic and well-publicized <a href="https://www.aging.senate.gov/imo/media/doc/Drug%20Pricing%20Report.pdf">spikes
in the price of a small number of generic drugs</a>, the problem with
prescription drug pricing has very little to do with the speed of entry into
the generic market and has much more to do with the marketing-driven sales of
branded drugs. The FDA has proposed nothing in that regard nor is there anything
yet proposed by the Trump Administration in that direction.</span><span style="mso-fareast-font-family: "Times New Roman";"><o:p></o:p></span></div>
Bob Bohrerhttp://www.blogger.com/profile/17081349778121412450noreply@blogger.com0tag:blogger.com,1999:blog-4025562924044932702.post-216184890648314482017-06-26T13:40:00.001-07:002017-06-26T13:40:20.204-07:00BIO 2017: Part I ––Virtual Development Is A Reality. <div class="MsoNormal">
I attended the big BIO Annual Meeting, which I had not
attended for several years, which was held this year in San Diego from June
19-22. As always, BIO is a great place to get a sense of the overall state of
the Pharma world and pick the brains of some very smart people. My perception
of people in the life science world has always been that the great majority are
remarkably willing to share their own knowledge and insights and this year’s
meeting reinforced that perception. It also reinforced my impression that the
biotech industry folks party a good deal harder than the law professors with
whom I generally hang out, but that would be the subject of a different blog.<o:p></o:p></div>
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<br /></div>
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As longer-term readers of this blog know, I have had a
continuing interest in the topic of biosimilars––particularly in the question
of whether one or more significantly different business models for biosimilar
development would be feasible and more cost-effective from a patient and
insurer perspective. To put this in perspective, we can use the example of <a href="https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/103772s5370lbl.pdf">Remicade/
infliximab</a>. Remicade is an antibody that binds to the protein TNFα and
prevents TNFα from delivering its inflammation-stimulating message. Remicade
was one of the first TNFα blocking drugs (others include Enbrel and Humira) and
it has been approved for use in a number of severe inflammatory diseases,
including Crohn’s disease, ulcerative colitis, and rheumatoid arthritis.<span style="mso-spacerun: yes;"> </span>The FDA has already granted Pfizer approval
to market <a href="https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm494227.htm">Inflectra,
a biosimilar Remicade</a> (yes, Pfizer the pharmaceutical behemoth, is in the
biosimilars space). If I wanted to start a virtual biosimilar company and
develop my own biosimilar Remicade (why wouldn’t I want to go head to head
in the marketplace with Pfizer?) who are all the people and service providers I
would need? One of my main goals at this year’s BIO meeting was to learn as
much as I could about the availability of the various kinds of expertise and
services that are required to take the development of a biosimilar from a
proposal to an FDA approved product. Could a small, virtual company produce a
biosimilar Remicade that could be approved by the FDA?<span style="mso-spacerun: yes;"> </span><o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
The first step in developing a biosimilar is to create a
cell-line (most-likely using Chinese Hamster Ovary, or CHO cells) that has been
engineered to efficiently produce an lgG1:Κ<o:p></o:p></div>
<div class="MsoNormal">
(that describes the genus of antibody to which infliximab
belongs) protein that is highly similar in structure and activity to the
original Remicade produced by Janssen. This first step requires sophisticated
expertise in protein engineering and analysis. Is this expertise available on a
contract basis? Can I find a CDO or CMO that can start at the very beginning
and provide me with my starting point of a cell-line to begin further
development? The answer I got at BIO2017 was “yes.” There are absolutely
companies out there that will provide me with a cell-line that has been
engineered to produce my biosimilar and that has been analyzed by a variety of
means as being structurally similar, with the correct glycosylation, comparable
affinity for the target protein, and pharmacokinetics in an appropriate in vivo
model. Immunogenicity analysis is a bit more complicated, but it would and
could be begun in the earliest phase of limited human clinical testing.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
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The second step is hiring the expertise to guide the
development through the regulatory process, from preclinical testing through
clinical testing and the requisite regulatory filings. There was a covey of
CROs (terrible wordplay intended) hawking (insert another groan here) exactly those
capabilities at BIO 2017. At the same time, the actual manufacturing, from pilot-scale
to market-scale, could be contracted for (and likely from the same company that
did the development and analysis of the master cell-line). At the end of the
day (or weeks of RFPs and negotiations) all the steps could absolutely be set
in motion. All the parts necessary to develop, manufacture, and license our
biosimilar Remicade would be in place and all that would remain are a
relatively low risk of failure in the clinic, worries about being sued for
infringement of some number of process patents by Janssen (a flurry of such
biosimilars infringement suits was predicted by retired U.S. District Court
Judge Faith Hochberg at BIO 2017), and finding a buyer or buyers.<span style="mso-spacerun: yes;"> </span>I’ll discuss the risk of failure,
infringement, and marketing issues in Part II of Virtual Development.<o:p></o:p></div>
Bob Bohrerhttp://www.blogger.com/profile/17081349778121412450noreply@blogger.com0tag:blogger.com,1999:blog-4025562924044932702.post-35671475534173906012017-06-14T20:18:00.000-07:002017-06-14T20:18:18.633-07:00More Ado About Prices<div class="MsoNormal">
It is almost impossible to read the news today without
coming across an article about the high prices of drugs and various approaches
to bringing drug prices down. I have discussed the general problem of drug
prices in previous posts (<a href="http://pharmaceuticalpolicy.blogspot.com/2014/04/drug-prices-and-pharmaceutical-market.html">Drug
Prices and the Pharmaceutical Market</a>, <a href="http://pharmaceuticalpolicy.blogspot.com/2014/07/pharmaceutical-pricing-story-that-just.html">Pharmaceutical
Pricing-- The Story That Just Keeps Going</a>, and <a href="http://pharmaceuticalpolicy.blogspot.com/2014/10/what-market-will-bear-pricing-pressures.html">What
the Market Will Bear: Pricing Pressures and Pharmaceutical Value</a>). However,
in today’s post I will briefly discuss two very different developments in the
drug-pricing story. The first is a resolution aimed at pricing that was
recommended for adoption by the American Medical Association (AMA) House of
Delegates. The second development is the growing concern over the
difficult-to-gauge gap between the list or “retail” price of drugs and the
actual amounts paid by different payors.<o:p></o:p></div>
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On the first development, the AMA House of Delegates <a href="https://www.ama-assn.org/sites/default/files/media-browser/public/hod/a17-refcommb-annotated.pdf">recently
supported the adoption</a> of Resolution 236 <i style="mso-bidi-font-style: normal;">Retail Price of Drugs Displayed in Direct-to-Consumer Pharmaceutical
Advertising</i>. The text of the resolution as adopted is brief:<o:p></o:p></div>
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Resolution 236 asks that our American
Medical Association advocate to the applicable Federal agencies (including the
Food and Drug Administration, the Federal Trade Commission, and the Federal
Communications Commission) which regulate or influence direct-to-consumer
advertising of prescription drugs that such advertising should be<o:p></o:p></div>
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required to state the manufacturer’s
suggested retail price of those drugs. <o:p></o:p></div>
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The AMA is a powerful lobbying group, but it raises the
question of whether the FTC or the FDA has any authority to require the
disclosure of retail prices in direct-to-consumer (DTC) advertising of
prescription drugs. My quick response would be no–– neither the FDA nor the FTC
has such authority. The FTC’s <a href="https://www.ftc.gov/about-ftc/bureaus-offices/bureau-consumer-protection/our-divisions/division-advertising-practices">Division
of Advertising Practices</a> “protects consumers from unfair or deceptive
advertising and marketing practices that raise health and safety concerns, as
well as those that cause economic injury.” Accordingly, <a href="https://www.ftc.gov/sites/default/files/documents/advocacy_documents/ftc-staff-comment-food-and-drug-administration-matter-direct-consumer-promotion/v960001.pdf">from
the very beginning of DTC prescription drug ads</a>, the FTC has aimed at
ensuring that consumers are not misled or deceived: “In particular, it is
important to protect consumers from deceptive information but not to stifle
truthful information that could benefit consumers.” There is almost no chance
that the FTC would find that an ad is deceptive or misleading because it fails
to state the price of the item advertised. Similarly, the FDA’s focus in
prescription drug advertising also is on ensuring that the ads are not
misleading (and that they do not suggest the product can be used for conditions
for which the FDA has not approved the drug). In my recent post on DTC ads <a href="http://pharmaceuticalpolicy.blogspot.com/2017/03/a-better-balance-between-accelerated.html">A
Better Balance Between Accelerated Access And High-Priced New Drugs: A New
Conditional Approval Option</a> I made the argument that those ads are
generally misleading with respect to the effectiveness of the advertised drugs.
So while it is significant that the AMA is continuing to express its concern
about prescription drug prices, this particular action by the AMA is not likely
to have any effect at all.<o:p></o:p></div>
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The other development I will briefly discuss in this post is
the growing awareness of the gap between retail prices (such as those the AMA
would like to see disclosed in DTC ads) and the prices actually paid by a
variety of payors (the “price gap”). How big is the price gap? QuintilesIMS
Institute addressed the question in its Annual Report <i style="mso-bidi-font-style: normal;"><a href="http://www.imshealth.com/en/thought-leadership/quintilesims-institute/reports/medicines-use-and-spending-in-the-us-review-of-2016-outlook-to-2021">Medicines
Use and Spending in the U.S.</a></i> (May 2017). The executive summary of the
report began with what is truly the bottom line:<o:p></o:p></div>
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Spending on medicines increased by 5.8%
to $450Bn in 2016, growing at less than half the rate seen in the last two
years, based on invoice prices. After adjusting for estimated rebates and other
price concessions by manufacturers, which continued to rise in 2016, net
spending was $323Bn, up 4.8% over 2015 levels. When adjusted for these
concessions, as well as economic and population growth, medicine spending
increased 2.6% in 2016 and has increased by an average of 1.1% per year since
2006, while the balance of medicines being used has shifted strongly to
specialty medicines from traditional treatments. <o:p></o:p></div>
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<br /></div>
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The Report then went on to summarize its findings with
respect to year-over-year increases for drugs already in the market:<o:p></o:p></div>
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<br /></div>
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The average net price for brands
already in the market is estimated to have increased by 3.5% in 2016, up from
2.5% in 2015, while remaining significantly lower than prior years. This reflects
the heightened competition among manufacturers and more aggressive efforts by
health plans and pharmacy benefit managers to limit price growth. <b style="mso-bidi-font-weight: normal;">Invoice price levels, prior to the impact
of concessions, increased 9.2% in 2016…. </b>[emphasis added.]<o:p></o:p></div>
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What are the takeaways from the
IMSQuintiles Report? The ridiculous annual increases in retail prices for
existing drugs (the 9.2% in the Report) are the attention-grabbing headlines of
a <a href="http://www.rheumatologyadvisor.com/practice-management/increased-prices-of-existing-drugs-driving-growth-of-drug-expenditures-in-2016/article/511580/">number
of stories on drug prices</a>, but only the starting point for the price
negotiations with payers and pharmacy benefit managers (PBMs). The price gap is
a much more complicated part of the drug pricing story, which is closely linked
to another major part of the pharmaceutical marketplace, the role of PBMs. Back
in March, <a href="https://www.bloomberg.com/news/articles/2017-03-15/middlemen-s-secret-drug-rebates-targeted-by-senator-wyden-s-bill">Bloomberg
BNA reported</a> that Senator Wyden (D.Ore) “proposed legislation that would
force drug middlemen to disclose secret discounts they receive from
manufacturers, a sign of growing scrutiny of the role played by pharmacy
benefit managers in high prices.” Wyden’s proposal, <i style="mso-bidi-font-style: normal;"><span style="mso-bidi-font-weight: bold;"><a href="https://www.congress.gov/bill/115th-congress/senate-bill/637">S.637 -
Creating Transparency to Have Drug Rebates Unlocked (C-THRU) Act of 2017</a></span></i><span style="mso-bidi-font-weight: bold;"> is, as the title suggests, about increasing
transparency in prices (for Medicare Part D drugs), which in theory can lead to
more negotiating power on the buyer side and lead to lower prices overall. This
kind of transparency in the prices actually charged for drugs is very different
from the “transparency” that is the subject of a <a href="http://catalyst.nejm.org/can-transparency-legislation-help-control-medication-costs/">number
of state laws seeking to require disclosure of the costs of developing
individual drugs</a>. Sarpatwari et al <a href="http://www.nejm.org/doi/pdf/10.1056/NEJMp1605100">reviewed those initiatives</a>
in The New England Journal of Medicine and pointed out the conceptual and
practical difficulties with “cost of development” disclosure mandates. My own
analysis is that transparency in the actual prices paid, which is the focus of
the Wyden proposal would be helpful. Marketplaces require information to work. While
much of the information needed for the pharmaceutical marketplace to work is
information about the actual effectiveness of a drug, prices paid by other parties
is also extremely useful. The problem of rising drug costs is unlikely to be
solved by information about prices, but it would at least be a step in the
right direction.<o:p></o:p></span></div>
Bob Bohrerhttp://www.blogger.com/profile/17081349778121412450noreply@blogger.com0tag:blogger.com,1999:blog-4025562924044932702.post-91625786231305150172017-06-12T22:14:00.001-07:002017-06-12T22:14:42.205-07:00U.S. Supreme Court Issues Opinion in Sandoz v. Amgen: A Big Win for Sandoz and Other Biosimilar Applicants.The U.S. Supreme Court released its much-anticipated ruling
today in the battle between Sandoz and Amgen over Amgen’s biosimilar version of
Sandoz’s Neupogen (filgrastim). Justice
Thomas’s opinion for a unanimous Court was an almost total victory for Amgen. Justice
Breyer issued a very brief one-page opinion concurring in the decision but expressing
his view that in future cases deference should be given to the FDA’s reasonable
interpretation of the <a href="https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/ucm216146.pdf">Biologics
Price Competition and Innovation Act of 2009</a> (the Act).<br />
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There were two major issues decided by the Court today. The
first was whether or not Sandoz fulfilled the 180-day notice requirement of the
Act when it delivered its original 180-day notice of its intent to market a
biosimilar filgrastim at the time of filing its application with the FDA. The
second major issue decided was whether the Act’s elaborate provisions providing
for exchanges of information (the “patent dance”) is mandatory. In the patent
dance the specifying the biosimilar applicant can provide its manufacturing
information to the reference drug sponsor followed the reference drug sponsor’s
provision of lists of patents it claims
are infringed by the biosimilar applicant <o:p></o:p></div>
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The answer to both these questions favored Sandoz. The
original 180-day notice of intent to market that Sandoz provided at the time of
filing its original application with the FDA was sufficient. No subsequent, second such notice was
required. The relevant language of the opinion on that clause is:<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal" style="margin-bottom: .0001pt; margin-bottom: 0in; margin-left: .5in; margin-right: .5in; margin-top: 0in;">
The Federal Circuit held that an
applicant’s biosimilar must already be “licensed” at the time the applicant
gives notice. 794 F. 3d, at 1358.<o:p></o:p></div>
<div class="MsoNormal" style="margin-bottom: .0001pt; margin-bottom: 0in; margin-left: .5in; margin-right: .5in; margin-top: 0in;">
We disagree. The applicant must give
“notice” at least 180 days “before the date of the first commercial marketing.”
<o:p></o:p></div>
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<br /></div>
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The provision of manufacturing information by the biosimilar
applicant and patent lists by the reference drug sponsor is not mandatory. The
remedy for the biosimilar applicant’s failure to provide the information that the Act provides is that the filing of
the biosimilar application is an act of infringement enabling the reference
drug sponsor to file suit. Here is the relevant language of that portion of the
opinion.<o:p></o:p></div>
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<br /></div>
<div class="MsoNormal" style="margin-bottom: .0001pt; margin-bottom: 0in; margin-left: .5in; margin-right: .5in; margin-top: 0in;">
Clause (ii) of §271(e)(2)(C), in
contrast, defines artificial infringement in the situation where an applicant
fails to disclose its application and manufacturing information altogether and
the parties never prepare the §262(<i>l</i>)(3) lists. That clause provides
that the submission of the application represents an act of artificial infringement
with respect to any patent that <i>could </i>have been included on the lists. <o:p></o:p></div>
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The Court did, however, leave a very small opening for Amgen
to snatch victory from the jaws of defeat. While Amgen was not entitled to an automatic
injunction under the biosimilar Act, on remand the U.S. District Court must
determine (again, from Justice Thomas’s opinion):<o:p></o:p></div>
<div class="MsoNormal">
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whether California law would treat
noncompliance with §262(<i>l</i>)(2)(A) as “unlawful.” If the answer is yes,
then the court should proceed to determine whether the BPCIA pre-empts any
additional remedy available under state law for an applicant’s failure to
comply with §262(<i>l</i>)(2)(A) (and whether Sandoz has forfeited any
pre-emption defense, see 794 F. 3d, at 1360, n. 5). The court is also of course
free to address the pre-emption question first by assuming that a remedy under
state law exists.<o:p></o:p></div>
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I would predict the District Court will not issue an
injunction based on California law and Amgen’s only recourse is to continue with
its infringement suit.<o:p></o:p></div>
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<br /></div>
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<br /></div>
<!--EndFragment-->Bob Bohrerhttp://www.blogger.com/profile/17081349778121412450noreply@blogger.com0tag:blogger.com,1999:blog-4025562924044932702.post-66189236842158189192017-06-06T12:21:00.000-07:002017-06-06T12:21:20.614-07:00Good News for Sickle-Cell Patients, But How Will Emmaus Make Money? A Look at the Business Side of Pharmaceutical Policy<div class="MsoNormal">
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<o:p> </o:p>Last week’s most interesting story was that a the <a href="http://www.healio.com/hematology-oncology/hematology/news/online/%7Badc7bff3-d069-4fcf-b7f9-8d406fe8d21c%7D/fda-advisory-committee-expresses-support-for-l-glutamine-for-sickle-cell-disease">FDA
Oncologic Drug Advisory Committee voted 10-3 to recommend that the FDA approve
Emmaus Medical’s L-Glutamine for the treatment of Sickle Cell Disease</a>. The Phase III Clinical Trial showed that
patients receiving L-Glutamine <a href="https://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/oncologicdrugsadvisorycommittee/ucm559736.pdf">had
a clinically significant reduction in the number of Sickle Cell Crises over the
course of the 48-week trial</a>. There were also positive results on other
measures of the drug’s benefit, while the safety issues were relatively minor. So
this is good news for Sickle Cell Disease patients. There are few therapeutic
options for this serious disease and the likely approval of another meaningful
treatment may make a real difference in their lives. </div>
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<o:p></o:p></div>
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BUT, this is one of the most unusual drug development
studies I have seen. While other Orphan Drug makers have taken older compounds
through development and relied on the 7 years of Orphan Drug exclusivity to
return a profit on their investment, L-Glutamine is not just an older compound.
Unlike repurposed older drugs, it is widely available and used as a dietary
supplement. So while Emmaus is to be commended for undertaking the costly and
risky process of establishing the effectiveness of L-Glutamine for Sickle Cell
Disease and will be the only manufacturer allowed to label L-Glutamine for
treating Sickle Cell Disease, they will not be the only manufacturer selling
L-Glutamine in bulk quantities sufficient to treat Sickle Cell Disease. A quick
search online revealed numerous online sellers.<span style="mso-spacerun: yes;">
</span>For example<a href="https://www.nutrivitashop.com/products/100-pure-micronized-l-glutamine-powder-pharmaceutical-pro-formulated">,
one online seller is offering 250 grams of L-Glutamine (advertised as
pharmaceutical-grade) for $9.95</a>.<span style="mso-spacerun: yes;">
</span>Since the Emmaus studies dosed patients at between 20 to 60 grams a day,
depending on body weight, the 250 grams being sold online would be last between
4 to 12.5 days.<span style="mso-spacerun: yes;"> </span>Even assuming that most
patients require 60 grams per day, the price for 1800 grams online would be a
bit more than $60 per month.<span style="mso-spacerun: yes;"> </span>I have not
yet seen an announcement of Emmaus’ intended pricing for their product
post-approval, however, <a href="https://www.rxpricequotes.com/">their current
pricing for the same drug, approved for short bowel syndrome, would be over $2000
per month at the higher dose</a>.<span style="mso-spacerun: yes;"> </span>While
the Rx form is likely to be covered by insurance, it still seems quite possible
that a significant market share could be lost to patients simply buying
L-Glutamine online. That would still be good for patients, but not very good
for Emmaus’ bottom line. It will be very interesting to follow Emmaus’ sales
over the next few years to see whether taking a dietary supplement through the
FDA approval process can actually work for companies as well as patients.<span style="font-family: Times; font-size: 10.0pt; mso-fareast-font-family: "Times New Roman";"><o:p></o:p></span></div>
Bob Bohrerhttp://www.blogger.com/profile/17081349778121412450noreply@blogger.com0tag:blogger.com,1999:blog-4025562924044932702.post-78603503297355073692017-05-26T17:11:00.000-07:002017-05-26T17:11:03.282-07:00More on New Developments at the FDA in the Era of Precision Medicine<div class="MsoNormal">
This week the FDA <a href="https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm560167.htm">approved
the expanded use of the cancer drug Keytruda for any solid tumor that expresses
a particular molecular marker</a>. It is the first time that the FDA has
approved new uses of a cancer drug in cancers that are defined by a molecular
marker independent of the site in the body where the tumor originated. While
the expanded use of the drug was based on an accelerated approval supported by
surrogate markers, this is another demonstration of the FDA’s continuing
adaptation to the new era of precision medicine, in which the appropriate use
of a drug is defined by particular genetic and molecular markers rather than
the broad traditional disease categories.<o:p></o:p></div>
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<i style="mso-bidi-font-style: normal;">Postscript to last
week’s post</i>–– I wrote that the approval of Kalydeco for cystic fibrosis
patients with 23 additional mutations was, to my knowledge, the first time ever
that the FDA had approved new indications for a drug without any human clinical
data. The Kalydeco label change was based entirely on an in vitro assay of the
drug’s effect on the function of the cystic fibrosis transmembrane receptor. The
in vitro assay had correlated well with clinical trial data from the original
Kalydeco studies and provided a reasonable degree of confidence that the drug
would work in the additional mutations tested. Later <a href="http://www.raps.org/Regulatory-Focus/News/2017/05/19/27615/FDA-Details-How-Kalydecos-Indication-Expanded-Without-New-Clinical-Data/">reports
and an additional statement from the FDA</a> confirmed my initial conclusion
that this approval was indeed the first of its kind and a real breakthrough in
drug approval. That is good news for the approximately 900 cystic fibrosis
patients who have one of those 23 mutations. Of course the 900 patients covered
by the 23 additional mutations means that there is, on average, fewer than 40
patients with any one of those mutations, which is why the FDA’s flexibility is
so important. Precision medicine will need that kind of regulatory innovation
to move forward when, as the FDA’s Janet Woodcock stated, there is a solid
understanding of the disease’s biology, a drug with a known safety (and pharmacokinetic)
profile, and a good assay to predict the drug’s effect in target populations.<o:p></o:p></div>
Bob Bohrerhttp://www.blogger.com/profile/17081349778121412450noreply@blogger.com0tag:blogger.com,1999:blog-4025562924044932702.post-3624668742022289292017-05-18T13:51:00.000-07:002017-05-18T13:54:34.751-07:00A milestone for precision medicine and for the FDA<div class="MsoNormal">
Precision medicine is much in the <a href="http://www.healthcareitnews.com/news/1-million-patient-cohort-being-prepared-fuel-precision-medicine-knowledge-base">news</a>––and
the need to target the right drug to the right patient using genomic and other
information is clearly going to be major part of healthcare in the future. Today's
news included an <a href="https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm559212.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery">announcement</a> from
the FDA that it had expanded the approved indications for Kalydeco, <span style="mso-spacerun: yes;"> </span>a breakthrough drug for the treatment of
cystic fibrosis.<span style="mso-spacerun: yes;"> </span>The previous <a href="https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/203188s022l_207925s003lbl.pdf">label</a>
indication described Kalydeco as a <o:p></o:p></div>
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<br /></div>
<div class="MsoNormal" style="margin-bottom: .0001pt; margin-bottom: 0in; margin-left: .5in; margin-right: .5in; margin-top: 0in;">
cystic fibrosis transmembrane
conductance regulator (CFTR) potentiator indicated for the treatment of cystic
fibrosis (CF) in patients age 2 years and older who have one of the following
mutations in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N,
S1255P, S549N, or S549R …[or] R117H<o:p></o:p></div>
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<br /></div>
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The new label, according to the FDA, expands the use of
Kalydeco from the 10 mutations above to include an additional 23 mutations, for
a total of 33.<span style="mso-spacerun: yes;"> </span>This is great news for
cystic fibrosis patients, as the clinical studies in the original population
showed that treatment with Kalydeco resulted in a significant increase in
patients’ lung function. From a precision medicine perspective the Kalydeco
expanded label could be viewed simply as yet another drug label with genomic
information about the drug’s appropriate use—after all, there are already well
over <a href="https://www.pharmgkb.org/view/drug-labels.do">200 drugs approvedby the FDA that include pharmacogenomic information</a>.<span style="mso-spacerun: yes;"> </span>However, it isn’t just the dramatic increase
in the number of mutations in the Cystic Fibrosis Transmembrane Receptor gene
that makes the FDA’s announcement remarkable, it is the evidentiary basis on
which the dramatic expansion in the use of Kalydeco was approved.<span style="mso-spacerun: yes;"> </span>The FDA’s announcement also had this particularly
noteworthy statement:<o:p></o:p></div>
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<br /></div>
<div class="MsoNormal" style="margin-bottom: .0001pt; margin-bottom: 0in; margin-left: .5in; margin-right: .5in; margin-top: 0in;">
Results from an in vitro cell-based
model system have been shown to reasonably predict clinical response to
Kalydeco. When additional mutations responded to Kalydeco in the laboratory
test, researchers were thus able to extrapolate clinical benefit demonstrated
in earlier clinical trials of other mutations. This resulted in the addition of
gene mutations for which the drug is now indicated.<o:p></o:p></div>
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In other words, the indication for
Kalydeco was approved solely on the basis of in vitro studies without
additional human clinical data (or animal data for that matter).<span style="mso-spacerun: yes;"> </span>Vertex Pharmaceuticals, the maker of
Kalydeco, was able to persuade the FDA that because there was a sufficiently high
correlation between the in vitro assays and clinical data for the previously
studied mutations, it was more than reasonable to allow the drug to be used for
patients with 23 additional mutations that showed a significant gain in
function in cell-based assays.<span style="mso-spacerun: yes;"> </span>I am
unaware of any similar action by the FDA. <span style="mso-spacerun: yes;"> </span>So the Kalydeco announcement is more than
another step in the targeting of drugs based on individual biomarkers, it is a
major step by the FDA in regulatory flexibility in streamlining drug development
as the science of predicting drug response evolves.<span style="mso-spacerun: yes;"> </span>We are indeed at the beginning of an
interesting journey on an uncharted road to the future of drug development.<o:p></o:p></div>
Bob Bohrerhttp://www.blogger.com/profile/17081349778121412450noreply@blogger.com1tag:blogger.com,1999:blog-4025562924044932702.post-10224779545349617942017-03-21T16:22:00.001-07:002017-03-21T16:22:51.143-07:00A Better Balance Between Accelerated Access And High-Priced New Drugs: A New Conditional Approval OptionThis entry is <a href="http://healthaffairs.org/blog/2017/03/20/a-better-balance-between-accelerated-access-and-high-priced-new-drugs-a-new-conditional-approval-option/">reposted</a> from Health Affairs Blog on March 20, 2017.<br />
<br />
<div class="MsoNormal" style="line-height: 150%;">
<span style="color: black; mso-fareast-language: JA; mso-themecolor: text1;">There are two different storms
brewing in the pharmaceutical world. On the one hand there is increasing opposition
to the very high prices of drugs. On the other hand there is ever more pressure
to accelerate access to drugs for seriously-ill patients. President Trump
expressed both of these very different concerns in </span><a href="https://www.washingtonpost.com/news/wonk/wp/2017/01/31/trump-calls-for-lower-drug-prices-fewer-regulations-in-meeting-with-pharmaceutical-executives/?utm_term=.b7d9ca5126c8"><span style="mso-fareast-language: JA;">his January 31st meeting with pharmaceutical
executives</span></a><span style="color: black; mso-fareast-language: JA; mso-themecolor: text1;">, during which he called drug prices “astronomical” while also vowing to
“streamline” the process of drug approval. It is vital that the cost of new
drugs not overwhelm patients and the health care system. It is also important
to get drugs to desperate patients as quickly as possible. <o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<span style="color: black; mso-fareast-language: JA; mso-themecolor: text1;">However,
accelerated access allows a drug to reach the market quickly, based on clinical
trials that measure </span><a href="https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=729831"><span style="mso-fareast-language: JA;">surrogate endpoints</span></a><span style="color: black; mso-fareast-language: JA; mso-themecolor: text1;">, for instance
time to cancer progression or observed tumor response rates, rather than
survival rates. These surrogate endpoints frequently </span><a href="http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2323416?alert=1"><span style="mso-fareast-language: JA;">fail to predict</span></a><span style="color: black; mso-fareast-language: JA; mso-themecolor: text1;"> whether
patients will actually live longer or have a better quality of life, but are
used because they can be measured within a relatively short period of time,
while evidence as to the real effectiveness of a drug can take years to
collect. At the same time, any reasonable approach to drug pricing requires substantial
knowledge of a drug’s effectiveness for its value to be considered when
evaluating the drug’s price and that knowledge simply is not available when a
drug is approved before its performance is known on truly meaningful endpoints such
as overall survival (in cancer) or long-term ability to function (in diseases
such as Parkinson’s or Muscular Dystrophy. With Congress and the President both
seeking to change the current system, there may be an opportunity to pursue a
different approach to accelerated approval and, at the same time, take at least
a small step towards reducing the costs of new, potentially life-saving drugs. One
way to strike a better balance between accelerated access and limiting drug
prices until their value is known might be a new form of “conditional approval”
with prices discounted until full approval is warranted.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; text-indent: .5in;">
<br /></div>
<div class="MsoNormal" style="line-height: 150%;">
<b style="mso-bidi-font-weight: normal;"><span style="color: black; mso-fareast-language: JA; mso-themecolor: text1;">The Issues with Accelerated Approval<o:p></o:p></span></b></div>
<div class="MsoNormal" style="line-height: 150%;">
<span style="color: black; mso-fareast-language: JA; mso-themecolor: text1;"><span style="mso-tab-count: 1;"> </span>The
FDA’s accelerated approval of eteplirsen, a new antisense drug for Duchenne
Muscular Dystrophy (DMD), is a clear example of both problems</span><span style="color: black; font-family: "ms ゴシック"; mso-hansi-font-family: "MS ゴシック";">——</span><span style="color: black; mso-fareast-language: JA; mso-themecolor: text1;">“astronomical
prices” and accelerated access. DMD is a devastating illness that affects
children and causes muscle weakness and eventual death. There are no effective
treatments. Understandably there was enormous pressure from patient groups to
approve the drug despite the lack of evidence that the drug actually works, </span><a href="http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm521263.htm"><span style="mso-fareast-language: JA;">beyond a change in a surrogate marker</span></a><span style="color: black; mso-fareast-language: JA; mso-themecolor: text1;">. <o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%;">
<span style="color: black; mso-fareast-language: JA; mso-themecolor: text1;">The drug is now available at a
price of $300,000 per patient per year, but it may be years before the data
from additional clinical trials can provide substantial evidence of whether or
not the drug is effective. If the drug turns out not to provide meaningful
clinical benefit, then the $300,000 per year cost of providing patients the
drug is a terrible waste of our health care dollars. However, if insurers do
not pay for the drug and it actually would provide significant therapeutic
benefit to Duchenne’s patients, then there would be even more terrible
unnecessary suffering and death among DMD patients.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%;">
<span style="color: black; mso-fareast-language: JA; mso-themecolor: text1;"><span style="mso-tab-count: 1;"> </span>Eteplirsen
is not by any means the only drug approved </span><a href="http://www.nejm.org/doi/full/10.1056/nejmhle1311493#t=article"><span style="mso-fareast-language: JA;">before the real risks were known or, in some
cases, a lack of real efficacy was demonstrated</span></a><span style="color: black; mso-fareast-language: JA; mso-themecolor: text1;">. One useful
model for accelerated access and controlled pricing was developed in response
to an earlier era of crisis in pharmaceutical policy when the HIV epidemic
first caused a public outcry for accelerated access. Prior to the AIDS crisis
of the 1980s, major patient advocacy groups, such as the American Cancer
Society and the American Heart Association, focused their efforts on raising
money for research and paid virtually no attention to the FDA. With AIDS, and
particularly with ACT UP (AIDS Coalition to Unleash Power), the world changed. For
the first time there was enormous pressure on the FDA to do something—anything—to
get drugs out to patients before all of the safety and efficacy data was in. <o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-layout-grid-align: none; mso-pagination: none; text-autospace: none;">
<span style="color: black; mso-fareast-language: JA; mso-themecolor: text1;"><span style="mso-tab-count: 1;"> </span>The FDA
responded to the AIDS crisis with a number of efforts to expand early access. One
that has the most relevance for today was the 1992 </span><a href="http://www.fda.gov/ForPatients/Illness/HIVAIDS/Treatment/ucm134331.htm"><span style="mso-fareast-language: JA;">parallel track initiative</span></a><span style="color: black; mso-fareast-language: JA; mso-themecolor: text1;">.<span class="MsoEndnoteReference"> </span>The </span><span style="mso-fareast-language: JA;">parallel track initiative<span style="color: black; mso-themecolor: text1;">, was
used only once for stavudine, a still-experimental drug that was made widely
available to physicians treating AIDS patients.<span style="mso-spacerun: yes;">
</span>The drug sponsor could seek to charge for the drug but only in an amount
sufficient to recover its costs for the trial, which required financial
disclosures to the FDA. Treating physicians providing the parallel track drug
were required to provide the sponsor with basic data on their patients and
patients’ responses to treatment.<o:p></o:p></span></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-layout-grid-align: none; mso-pagination: none; text-autospace: none;">
<br /></div>
<div class="MsoNormal" style="line-height: 150%; mso-layout-grid-align: none; mso-pagination: none; text-autospace: none;">
<b style="mso-bidi-font-weight: normal;"><span style="color: black; mso-fareast-language: JA; mso-themecolor: text1;">How Conditional
Approval Could Work<o:p></o:p></span></b></div>
<div class="MsoNormal" style="line-height: 150%; mso-layout-grid-align: none; mso-pagination: none; text-autospace: none;">
<span style="color: black; mso-fareast-language: JA; mso-themecolor: text1;"><span style="mso-tab-count: 1;"> </span>A
more balanced approach to the current cry for accelerated access and lower
prices could adapt and build on the 1992 HIV-only parallel track approach. The
two key components that could be revised for today’s use are: first, an accelerated
approval that permits wide distribution before final approval; and, second, a
mechanism that limits the price of the conditionally-approved drugs while more
data is collected. Conditional approval based on surrogate endpoints would
allow a drug’s sponsor to distribute the drug to all of the desperately ill
patients who have no alternative, while maintaining the price restrictions
until additional data on actual clinical benefit and risk is provided. This
would provide a 21<sup>st</sup> Century update of the 1992 HIV-only Parallel
Track.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-layout-grid-align: none; mso-pagination: none; text-autospace: none;">
<span style="color: black; mso-fareast-language: JA; mso-themecolor: text1;"><span style="mso-tab-count: 1;"> </span>Under
the conditional approval proposed here any physician treating a patient with
the targeted indication could prescribe the drug and would agree to collect and
report basic data on the duration of treatment, responses to the drug, and any
other changes in their patients’ conditions. Such longer-term single arm trials
are likely to provide evidence of real effectiveness and safety when the target
is an untreatable serious disease. While the drug is being widely used and the
data collected, the sponsor could charge for the drug based on a set price
formula until the sponsor provides further data and the FDA completes its
review. There would be no need for case-by-case negotiations over costs and
pricing as was required by the 1992 Parallel Track policy. This differs from other
accelerated access programs that use the term “conditional approval” (</span><a href="http://ec.europa.eu/health//sites/health/files/files/eudralex/vol-1/reg_2006_507/reg_2006_507_en.pdf"><span style="mso-fareast-language: JA;">such as that used by the European Medicines
Evaluation Agency</span></a><span style="color: black; mso-fareast-language: JA; mso-themecolor: text1;">, which does not limit prices and must be reviewed annually).<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-layout-grid-align: none; mso-pagination: none; text-autospace: none;">
<br /></div>
<div class="MsoNormal" style="line-height: 150%; mso-layout-grid-align: none; mso-pagination: none; text-autospace: none;">
<b style="mso-bidi-font-weight: normal;"><span style="color: black; mso-fareast-language: JA; mso-themecolor: text1;">Determining Prices
for Conditionally Approved Drugs<o:p></o:p></span></b></div>
<div class="MsoNormal" style="line-height: 150%; mso-layout-grid-align: none; mso-pagination: none; text-autospace: none;">
<span style="color: black; mso-fareast-language: JA; mso-themecolor: text1;"><span style="mso-tab-count: 1;"> </span>How
might the predetermined discounted price provision work? One possible mechanism
would require a pharmaceutical company seeking conditional approval to specify
its intended initial market price for the new drug. The conditional approval
distribution price could be limited to 25 percent of the specified initial
market price. Alternatively, the conditional approval price formula might be a predetermined
percentage of the average introductory price of breakthrough drugs approved
during the prior two years. Unlike the prior Parallel Track provisions, either
price formula would avoid the need for the sponsor to disclose its costs and
negotiate with the FDA to justify charging during the conditional approval
period. Given the strong demand by patients for a potentially life-saving drug when
there is no effective alternative, marketing expenses should be low. <o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-layout-grid-align: none; mso-pagination: none; text-autospace: none; text-indent: .5in;">
<span style="color: black; mso-fareast-language: JA; mso-themecolor: text1;">With the very low cost of small
molecule manufacture or even the higher costs of manufacturing biologic drugs,
the 25 percent pricing formula should cover the costs of manufacture,
distribution, a limited marketing outreach, and the process of data collection
and still provide a modest profit. This conditional approval update of Parallel
Track would provide the needed balance between access to potential breakthrough
drugs and substantial evidence to support their unrestricted entry into the
marketplace. Limiting profits would motivate drug companies to distribute the
drug widely enough to provide the needed evidence as expeditiously as possible.
And in an era of skyrocketing prices for new drugs it would avoid imposing even
greater costs to consumers and insurers for what are actually experimental
drugs such as eteplirsen. <o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 150%; mso-layout-grid-align: none; mso-pagination: none; text-autospace: none; text-indent: .5in;">
<b style="mso-bidi-font-weight: normal;"><span style="color: black; mso-fareast-language: JA; mso-themecolor: text1;">A Way Forward with Conditional Approval<o:p></o:p></span></b></div>
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<span style="color: black; mso-fareast-language: JA; mso-themecolor: text1;"><span style="mso-tab-count: 1;"> </span>New proposals
are being discussed that would even further accelerate access to new drugs and </span><a href="http://www.medpagetoday.com/Neurology/GeneralNeurology/63110"><span style="mso-fareast-language: JA;">members of both parties in the House and Senate
are moving forward with a variety of approaches to the high cost of new drugs</span></a><span class="MsoHyperlink"><span style="mso-fareast-language: JA;">.</span></span><span style="color: black; mso-fareast-language: JA; mso-themecolor: text1;"> Now is the
time to take a new approach to accelerating access and limiting drug prices. Of
course, it would also be necessary to require insurers and government payers to
cover the drugs during the conditional approval period in the same way that
they currently cover drugs approved under the accelerated access and
breakthrough drug procedures. If the data confirms the benefit of the
treatment, full approval would be granted and the drug sponsor could charge
whatever price it can justify in the marketplace, but with much better evidence
as to what the drug’s real worth actually is. Patients desperate for treatment
would get access to drugs, insurers would be paying less than under the current
system, and patients, providers and insurers would get the data they need on
the drug’s efficacy. It is time for a new approach to accelerated access that
is good for patients and good for us all. <o:p></o:p></span></div>
<br />
<br />
<br />Bob Bohrerhttp://www.blogger.com/profile/17081349778121412450noreply@blogger.com0tag:blogger.com,1999:blog-4025562924044932702.post-45340648082698952092015-05-28T13:30:00.001-07:002015-05-28T13:30:31.461-07:00The 2st Century Cures Act: Patient Experience in Drug Approval<div class="MsoNormal">
On Thursday, May 19, 2015, the Energy and Commerce Committee
of the House of Representatives voted 51 to 0 to approve the <a href="http://docs.house.gov/meetings/IF/IF00/20150519/103516/BILLS-114pih-DiscussionDraftof21stCent.pdf">21<sup>st</sup>
Century Cures Act</a> (“the Cures Act”) which would, if passed by the full
House and Senate and signed by the President bring about a number of significant
changes in NIH research funding, the process of drug development, and the FDA review
of New Drug Applications (“NDAs”). Because the current draft is 300
double-spaced pages in length the focus in this post will be on just six of
those pages--“<span style="mso-bidi-font-weight: bold;">Sec. 2001. Development
And Use Of Patient Experience Data To Enhance Structured Risk-Benefit
Assessment Framework.” While there are likely to be some changes to the current
draft, given the overwhelming bipartisan support in the House, it seems that
much, if not all, of the current draft will become law.<o:p></o:p></span></div>
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<span style="mso-bidi-font-weight: bold;">Section 2001 of the Curs
Act consists of two subsections, currently denominated (x) and (y).<span style="mso-spacerun: yes;"> </span>Section 2001 would appear to require very
little change to the current approach of the FDA to drug approval.<span style="mso-spacerun: yes;"> </span>Section 2001 Subsection x (1) states that
“The Secretary shall implement a structured risk-benefit assessment framework
in the new drug approval process [A] to facilitate the balanced consideration
of benefits and risks; and [B] to develop a consistent and systematic approach
to the discussion of…the benefits and risks of new drugs.” The current draft of
Sec. 2001 Subsection (x) 2 contains the proviso that “Nothing in Paragraph (1)
“shall alter the criteria for evaluating an application for premarket approval
of a drug.” The apparent focus of this subsection (x) is to bring greater
clarity and consistency to the FDA’s weighing of risks versus benefits. This is
an unobjectionable goal, if somewhat difficult to implement. For example, one
cancer drug may cause severe skin reactions while increasing overall survival
by one month, while another drug for the same form of cancer may cause severe
gastric effects while increasing overall survival by 1.2 months. Comparing the
risks and benefits of those two drugs is obviously difficult to do.<span style="mso-spacerun: yes;"> </span>It is that difficulty that may be the
objective of the much more interesting Subsection (y).<o:p></o:p></span></div>
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<span style="mso-bidi-font-weight: bold;">Subsection (y) is
entitled “Development And Use Of Patient Experience Data To Enhance Structured
Risk-Benefit Assessment Framework.”<span style="mso-spacerun: yes;"> </span>Subsection
(y) 1 requires the Secretary of HHS, over a period of 2 to 3 years, to a
promulgate a number of guidances and establish procedures by which non-NDA
sponsor entities may submit patient experience research proposals for feedback
from the Secretary as well as patient experience data and data analyses.<span style="mso-spacerun: yes;"> </span>Patient experience data, or, as it is also
known, patient-reported outcomes data has been a field of interest in clinical
research for a number of years. Patient-reported outcomes was the subject of an
FDA Guidance issued in 2009 (“2009 Guidance”). <span style="mso-spacerun: yes;"> </span>The 2009 Guidance recognized the value of
assessing patient experience endpoints in clinical trials and encouraged
patient input in developing the instruments to be used in assessing patient
reported outcomes or experience:<o:p></o:p></span></div>
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<div class="MsoNormal" style="margin-bottom: .0001pt; margin-bottom: 0in; margin-left: .5in; margin-right: .5in; margin-top: 0in;">
<span style="mso-bidi-font-weight: bold;">Item
generation should include input from the target patient population to establish
the items that reflect the concept of interest and contribute to its
evaluation. The population will help generate item wording, evaluate the
completeness of item coverage, and perform initial assessment of clarity and
readability. <o:p></o:p></span></div>
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<span style="mso-bidi-font-weight: bold;">However, the
approach to patient experience data in the Cures Act goes well beyond the 2009 Guidance.<span style="mso-spacerun: yes;"> </span>Subsection (y) provides the
Cures Act definition of patient experience data:</span><span style="font-family: Times; font-size: 19.0pt; mso-bidi-font-family: Times; mso-fareast-language: JA;"> </span><span style="mso-bidi-font-weight: bold;"><o:p></o:p></span></div>
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<span style="mso-bidi-font-weight: bold;">In
this subsection, the term ‘patient experience data’ means data collected by<i style="mso-bidi-font-style: normal;"> </i>patients, parents, caregivers, patient
advocacy organizations, disease research foundations, medical researchers,
research sponsors or other parties determined appropriate by the Secretary
that is intended to facilitate or enhance the Secretary’s risk-benefit
assessments, including information about the impact of a disease or a therapy on
patients’ lives. <o:p></o:p></span></div>
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<span style="mso-bidi-font-weight: bold;">The statutory
inclusion of data <i style="mso-bidi-font-style: normal;">collected by</i>
“patients, parents, caregivers, patient advocacy organizations, [and] disease
research foundations” is radically different from the drug-sponsor driven
approach that was addressed in the 2009 Guidance. Bringing data collected by
persons or entities other than the drug sponsor into the New Drug Approval process (or the sNDA process of approving additional indications or major label changes) would be a fundamental change in the concept of data to be used by the FDA in new drug review and would significantly increase the role of patients and
patient organizations in the drug approval process itself. <span style="mso-spacerun: yes;"> </span>If so, the 21<sup>st</sup> Century Cures Act’s
effect on drug development might be as dramatic as the title of the Cures Act
suggests.<o:p></o:p></span></div>
Bob Bohrerhttp://www.blogger.com/profile/17081349778121412450noreply@blogger.com0tag:blogger.com,1999:blog-4025562924044932702.post-65263727747968913722015-05-06T18:54:00.000-07:002014-05-06T19:10:30.903-07:00What Is Pharmaceutical Policy and What Is Its Goal?<div class="western" style="line-height: 200%; margin-bottom: 0in;">
<br></div>
<div class="western" style="line-height: 200%; margin-bottom: 0in; text-indent: 0.5in;">
Pharmaceutical policy is the role that government plays in
determining the rate at which new drugs are developed, what drugs are
developed, who has access to the drugs that are developed, and the
choice of drugs by doctors and their patients. The goal of
pharmaceutical policy is to provide the maximum benefit to health for
whatever amount is spent on pharmaceuticals. A good policy in any
area of health care will produce the most health at the least cost.
This first premise, although it may be new to some of you, is a
generally accepted premise of public policy analysis: more of a good
thing is better than less (whether it be educational levels, health,
or economic production) and getting more of a good thing at the least
cost is better, as that leaves the surplus to be allocated to
obtaining more of other good things (so getting more health for less
dollars would allow us to spend more on schools, for example).
</div>
<br>
<a href="http://pharmaceuticalpolicy.blogspot.com/2014/02/whatis-pharmaceutical-policy-and-what.html#more">Read more »</a>Bob Bohrerhttp://www.blogger.com/profile/17081349778121412450noreply@blogger.com2tag:blogger.com,1999:blog-4025562924044932702.post-79824425755030826892015-02-20T13:48:00.001-08:002015-02-20T13:48:50.005-08:00The Need For Publicly Funded Trials To Get Unbiased Comparative Effectiveness Data<div class="MsoNormal" style="margin-bottom: 12.0pt; mso-layout-grid-align: none; mso-pagination: none; text-autospace: none;">
By Bob Bohrer</div>
<div class="MsoNormal" style="margin-bottom: 12.0pt; mso-layout-grid-align: none; mso-pagination: none; text-autospace: none;">
<span style="font-family: Verdana; font-size: 9.0pt; mso-bidi-font-family: Verdana; mso-fareast-language: JA;">Originally Posted on <i>Health Affairs </i>by Robert Bohrer
On February 20, 2015 <a href="http://healthaffairs.org/blog/2015/02/20/the-need-for-publicly-funded-trials-to-get-unbiased-comparative-effectiveness-data/">http://healthaffairs.org/blog/2015/02/20/the-need-for-publicly-funded-trials-to-get-unbiased-comparative-effectiveness-data/</a></span></div>
<div class="MsoNormal" style="margin-bottom: 12.0pt; mso-layout-grid-align: none; mso-pagination: none; text-autospace: none;">
<span style="font-family: Verdana; font-size: 9.0pt; mso-bidi-font-family: Verdana; mso-fareast-language: JA;">Comparative effectiveness
research was one of the <span style="color: #0000e9;"><a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=Jerry+Avorn%2C+Debate+about+funding+comparative+effectiveness+research%2C+N.+Eng.+J.+Med.+++2009%3A+360(19)+1927-1929&report=abstract">hotly
debated components</a> </span></span><span style="font-family: Verdana; font-size: 8.0pt; mso-bidi-font-family: Verdana; mso-fareast-language: JA; mso-text-raise: 4.0pt; position: relative; top: -4.0pt;">[1] </span><span style="font-family: Verdana; font-size: 9.0pt; mso-bidi-font-family: Verdana; mso-fareast-language: JA;">of
the Affordable Care Act. The pharmaceutical industry is marketing driven, with
pharmaceutical companies <span style="color: #420178;"><a href="http://www.bbc.com/news/business-28212223">spending more on marketing</a>
</span></span><span style="font-family: Verdana; font-size: 8.0pt; mso-bidi-font-family: Verdana; mso-fareast-language: JA; mso-text-raise: 4.0pt; position: relative; top: -4.0pt;">[2] </span><span style="font-family: Verdana; font-size: 9.0pt; mso-bidi-font-family: Verdana; mso-fareast-language: JA;">than they do on research and development. The
need for a marketing edge can also drive drug development. </span><span style="font-family: Times; mso-bidi-font-family: Times; mso-fareast-language: JA;"><o:p></o:p></span></div>
<div class="MsoNormal" style="margin-bottom: 12.0pt; mso-layout-grid-align: none; mso-pagination: none; text-autospace: none;">
<span style="font-family: Verdana; font-size: 9.0pt; mso-bidi-font-family: Verdana; mso-fareast-language: JA;">As illustrated by the
discussion below of Gazyva and Nexium, drugs can be developed at higher doses
than the drugs they are intended to replace. When the newer, higher-dose drugs
are tested against the older, lower-dose drugs, the trials are intended to show
that the newer, higher dose drugs are superior to the older drugs that will
soon be available as a biosimilar or generic. </span><span style="font-family: Times; mso-bidi-font-family: Times; mso-fareast-language: JA;"><o:p></o:p></span></div>
<div class="MsoNormal" style="margin-bottom: 12.0pt; mso-layout-grid-align: none; mso-pagination: none; text-autospace: none;">
<span style="font-family: Verdana; font-size: 9.0pt; mso-bidi-font-family: Verdana; mso-fareast-language: JA;">It can be very difficult
to tell whether the results of such trials reflect the differences between the
active ingredients or simply the difference in doses, but such trials are almost
certain to lead to increased use of the newer, higher-priced drugs. Because the
money at stake creates such an incentive for companies to stack the deck,
publicly funded trials are the only way to make sure that evidence-based
medicine is based on the best possible evidence. <a href="https://www.dropbox.com/s/cdrm5xqkye34ks3/Health%20Affairs%20Blog%20%C2%BB%20The%20Need%20For%20Publicly%20Funded%20Trials%20To%20Get%20Unbiased%20Comparative%20Effectiveness%20Data%20%C2%BB%20Print.pdf?dl=0">PDF of this post</a></span></div>
<a href="http://pharmaceuticalpolicy.blogspot.com/2015/02/the-need-for-publicly-funded-trials-to_20.html#more">Read more »</a>Bob Bohrerhttp://www.blogger.com/profile/17081349778121412450noreply@blogger.com0tag:blogger.com,1999:blog-4025562924044932702.post-74434889284269275002014-12-07T14:20:00.001-08:002014-12-07T14:20:10.625-08:00Interesting Developments in November<br /><div class="MsoNormal">
<o:p> </o:p>I will be commenting soon on developments related to
pharmaceutical patents and their significance for personalized medicine, but in
this post I am briefly describing several interesting news items and articles
from various media sources, and I am attaching links to the stories and
articles.</div>
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<o:p></o:p></div>
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1.<span style="mso-spacerun: yes;"> </span>Jonathan Darrow
has written a great article entitled <i style="mso-bidi-font-style: normal;">Pharmaceutical
Gatekeepers </i>in the <span style="font-variant: small-caps;">Indiana Law Review</span>.<span style="mso-spacerun: yes;"> </span>Darrow looks at the variety of actors in the
drug-use decision-making process and their roles in the continued consumption
of ineffective drugs.<o:p></o:p></div>
<div class="MsoNormal">
<a href="http://mckinneylaw.iu.edu/ilr/pdf/vol47p363.pdf">http://mckinneylaw.iu.edu/ilr/pdf/vol47p363.pdf</a><o:p></o:p></div>
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2.<span style="mso-spacerun: yes;"> </span>The Tufts Center
for the Study of Drug Development has released its latest estimate of the cost
of developing a new drug and, as always, the estimate, $2.6 billion, is a
stunning one that has attracted widespread media attention.<span style="mso-spacerun: yes;"> </span>I think the most nuanced mass media report on
the study was written by Aaron E. Carroll and published in <span style="font-variant: small-caps;">The New York Times</span> on November 19th.<o:p></o:p></div>
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<a href="http://www.nytimes.com/2014/11/19/upshot/calculating-the-real-costs-of-developing-a-new-drug.html?module=Search&mabReward=relbias%3Ar%2C%7B%221%22%3A%22RI%3A6%22%7D&_r=0">http://www.nytimes.com/2014/11/19/upshot/calculating-the-real-costs-of-developing-a-new-drug.html</a><o:p></o:p></div>
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3. The issue of clinical trial data
sharing has been the focus of significant attention over the past several
years.<span style="mso-spacerun: yes;"> </span>In the November 27<sup>th</sup>
issue of <span style="font-variant: small-caps;">The New England Journal of
Medicine</span>, Brian L. Strom <i style="mso-bidi-font-style: normal;">et al </i>published
a report of the results of GlaxoSmithKline providing full access to its
clinical trial data as of May 2013, and the NIH has proposed a new rule
requiring increased access to clinical trial data summaries for all clinical
trials.<o:p></o:p></div>
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<br /></div>
<div class="MsoNormal" style="margin-right: -.5in;">
<span style="mso-tab-count: 1;"> </span>The
Strom article is here:<o:p></o:p></div>
<div class="MsoNormal" style="margin-right: -.5in;">
<span style="mso-tab-count: 1;"> </span><a href="http://www.nejm.org/doi/pdf/10.1056/NEJMp1411794">http://www.nejm.org/doi/pdf/10.1056/NEJMp1411794</a><o:p></o:p></div>
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<br /></div>
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<span style="mso-tab-count: 1;"> </span>The
NIH’s notice of its proposed rule is here:<o:p></o:p></div>
<div class="MsoNormal" style="margin-right: -.5in;">
<span style="mso-tab-count: 1;"> </span><a href="http://www.regulations.gov/#!documentDetail;D=NIH-2011-0003-0003">http://www.regulations.gov/#!documentDetail;D=NIH-2011-0003-0003</a><o:p></o:p></div>
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<br /></div>
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4.<span style="mso-spacerun: yes;"> </span>Finally, the issue of pharmaceutical pricing
continues to be in the news and on November 25th Robert Langreth of
Bloomberg/BNA published an interesting article on pushback by Express Scripts
and other pharmaceutical benefit managers (PBMs).<span style="mso-spacerun: yes;"> </span>The PBMs are revising their formularies and
their access requirements for specialty drugs in an effort to hold down
costs.<span style="mso-spacerun: yes;"> </span><o:p></o:p></div>
<div class="MsoNormal" style="margin-right: -.5in;">
<a href="http://www.bloomberg.com/news/print/2014-11-25/more-medicine-goes-off-limits-in-drug-price-showdown.html">http://www.bloomberg.com/news/print/2014-11-25/more-medicine-goes-off-limits-in-drug-price-showdown.html</a><o:p></o:p></div>
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Pricing has been the biggest
story in the pharmaceutical world in 2014, I expect that to continue in
2015.<span style="mso-spacerun: yes;"> </span>The PBMs’ efforts to hold down
prices and the soon to emerge marketplace for biosimilars in the U.S. will
certainly be an interesting part of the pricing story.<o:p></o:p></div>
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Bob Bohrerhttp://www.blogger.com/profile/17081349778121412450noreply@blogger.com0tag:blogger.com,1999:blog-4025562924044932702.post-35359223166399057542014-11-30T19:59:00.004-08:002014-11-30T19:59:55.447-08:00Update on Generics, Labeling, and Liability <div class="MsoNormal">
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I began this blog back in February of 2014 with two posts on
<a href="http://pharmaceuticalpolicy.blogspot.com/2014_02_01_archive.html">the
FDA’s proposed changes to the rules for generic labeling</a> and the issue of <a href="http://pharmaceuticalpolicy.blogspot.com/2014/03/an-estimate-of-pharmaceutical-industry_14.html">potential
liability of generic drug manufacturers for failing to strengthen their
warnings</a> when it would be appropriate to do so. Recent events related to
generic labeling and liability warrant a brief update on the issue. In
litigation over injuries allegedly attributable to Reglan and its generic form,
metoclopramide, a <a href="http://www.njlawarchive.com/201411121025051152576787/">New Jersey
appellate court has ruled</a> that generic manufacturers could be liable for
failure to warn when they had failed to update the label for their drugs even
after the brand name manufacturer had added a new warning.<span style="mso-spacerun: yes;"> </span>In other words, the New Jersey court held
that actions for failure to warn were not preempted under the rule in <a href="http://www.supremecourt.gov/opinions/10pdf/09-993.pdf"><i style="mso-bidi-font-style: normal;">Pliva v. Mensing</i>,</a> because in <i style="mso-bidi-font-style: normal;">Pliva </i>the defendants were required to
adhere to the brand name drug’s label and in the case of metoclopramide the
problem was the failure of some generic manufacturers to update their labels
when changes were made to the brand name label. <o:p></o:p></div>
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The second development on this issue is <a href="http://blogs.wsj.com/pharmalot/2014/11/18/fda-delays-final-rule-on-allowing-generic-drug-makers-to-update-labels/">the
news</a> that the FDA is postponing action to finalize the proposed rule.<span style="mso-spacerun: yes;"> </span>The FDA’s postponement of its final action on
the rule comes in the wake of an interview with <a href="http://www.raps.org/Regulatory-Focus/News/2014/10/07/20497/Generic-Drug-Industry-Threatens-FDA-With-Lawsuit-Over-Drug-Labeling-Proposal/"><span style="font-variant: small-caps;">Regulatory Focus</span></a> in which Ralph
Neas, the President of the Generic Pharmaceutical Manufacturers’ Association,
said that the Association was readying a lawsuit if the FDA adopted the
proposed rule. The FDA has only said that it had received a very large number
of comments on the proposed rule and that the Agency is committed to giving all
comments serious consideration. This issue remains a hot one and the recent
change in the balance of power in Washington only raises the temperature
further.<span style="mso-spacerun: yes;"> </span><span style="mso-spacerun: yes;"> </span><o:p></o:p></div>
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<o:p> </o:p> <a href="https://drive.google.com/file/d/0BxIAusggav4bT1ZNN29ja09sVHM/view?usp=sharing">Download PDF</a></div>
Bob Bohrerhttp://www.blogger.com/profile/17081349778121412450noreply@blogger.com0tag:blogger.com,1999:blog-4025562924044932702.post-36351475869411706332014-11-13T14:47:00.001-08:002014-11-13T14:47:27.180-08:00Profits, Ebola, and Biodefense-- Common Ground for the New Congress<div class="MsoNormal">
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In my post of November 6, 2014, I linked to <a href="http://www.bbc.com/news/business-28212223?">an interesting BBC story</a>
that pointed out that pharmaceutical companies are highly profitable in
comparison with other industries and that <a href="http://www.fiercepharma.com/story/new-numbers-back-meme-pharma-does-spend-more-marketing-rd/2014-11-06">pharmaceutical
companies generally spend more on marketing than on research and development</a>
(in the case of Pfizer 72% more and in the case of Novartis 47% more).<span style="mso-spacerun: yes;"> </span>This is unfortunate, but inevitable when
companies with very similar drugs and relatively little data that support a
physician’s preference for one drug over another are fighting for market
share.<span style="mso-spacerun: yes;"> </span>At the same time, pharmaceutical
companies are being criticized for their high prices and for their slow pace of
investment in developing drugs and vaccines for Ebola.<span style="mso-spacerun: yes;"> </span><span style="font-variant: small-caps;">The New
York Times </span>on October 24, 2014, provided extensive coverage of a number
of Ebola issues, including a <a href="http://www.nytimes.com/2014/10/24/health/without-lucrative-market-potential-ebola-vaccine-was-shelved-for-years.html">story
on a vaccine that had shown great effectiveness in a primate study</a> but then
had gone undeveloped for ten years.<span style="mso-spacerun: yes;"> </span>The
New York Times story pinned the blame for the delay in development on the lack
of a significant commercial market for the vaccine.<span style="mso-spacerun: yes;"> </span>The Director-General of the World Health
Organization (WHO), Dr. Margaret Chan, had this to say in her <a href="http://www.who.int/dg/speeches/2014/regional-committee-africa/en/">November
3<sup>rd</sup> address to the WHO Regional Committee to Africa</a>:<o:p></o:p></div>
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The second argument is this. Ebola
emerged nearly four decades ago. Why are clinicians still empty-handed, with no
vaccines and no cure? <o:p></o:p></div>
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<div class="MsoNormal" style="margin-bottom: .0001pt; margin-bottom: 0in; margin-left: .5in; margin-right: .5in; margin-top: 0in;">
Because Ebola has historically been
confined to poor African nations. The R&D incentive is virtually
non-existent. A profit-driven industry does not invest in products for markets
that cannot pay. WHO has been trying to make this issue visible for ages. Now
people can see for themselves. <o:p></o:p></div>
<div class="MsoNormal" style="margin-right: .5in;">
<a href="https://drive.google.com/file/d/0BxIAusggav4bNHhndWxyZUdGcEk/view?usp=sharing">Download
PDF</a><o:p></o:p></div>
<div class="MsoNormal" style="margin-right: .5in;">
</div>
<a href="http://pharmaceuticalpolicy.blogspot.com/2014/11/profits-ebola-and-biodefense-common.html#more">Read more »</a>Bob Bohrerhttp://www.blogger.com/profile/17081349778121412450noreply@blogger.com0tag:blogger.com,1999:blog-4025562924044932702.post-53009029341706513422014-11-06T15:39:00.002-08:002014-11-06T15:39:50.343-08:00Interesting BBC News Story on Pharma Profit Margins and Marketing ExpendituresThe story link is <a href="http://www.bbc.com/news/business-28212223?">here</a>. As I have often said on the subjects of profits, companies charge prices calculated to maximize their profits. And, as to the high marketing costs, when there isn't solid data to support a choice among similar drugs, marketing costs will inevitably rise.Bob Bohrerhttp://www.blogger.com/profile/17081349778121412450noreply@blogger.com0tag:blogger.com,1999:blog-4025562924044932702.post-10548670720937142782014-11-05T22:12:00.002-08:002014-11-05T22:12:43.153-08:00Personalized Medicine UpdatePersonalized medicine uses an individual patient’s
variations with respect to one or more biomarkers or combination of biomarkers
to determine which is the most appropriate pharmaceutical or medical
intervention. Such biomarkers can be
genetic variations or other variations.
In <i><a href="http://www.supremecourt.gov/opinions/11pdf/10-1150.pdf">Mayo
Collaborative Services v. Prometheus Laboratories</a></i> (<i>Mayo v. Prometheus</i>) the “biomarker” was the level of the metabolite
in a patient who had been given a thiopurine drug, and the Supreme Court held
that a patent that taught how to adjust the drug dosage after measuring the
metabolite was invalid as an attempt to patent a natural phenomenon. After one of Myriad Genetics’ patent claims
related to gene sequences used in its genetic test for breast cancer risk <a href="http://www.supremecourt.gov/opinions/12pdf/12-398_1b7d.pdf">was similarly
invalidated as a natural phenomenon or product of nature</a>, the biotech and
diagnostic industries were understandably concerned. Personalized medicine is clearly a vitally important
area for future healthcare and the extent to which the difficulty of obtaining
intellectual property protection for pharmacogenomic testing or other
personalized medicine assays could delay or undermine progress in the area is a
question of great importance. <span style="font-variant: small-caps;">The North Carolina Journal of Law and
Technology</span> recently devoted a symposium to the question of the
significance of the decision in the <i><a href="http://www.supremecourt.gov/opinions/12pdf/12-398_1b7d.pdf">Myriad</a></i>
case and Chris Holman’s <a href="http://ncjolt.org/wp-content/uploads/2014/07/Holman_Final.pdf">contribution
to that symposium</a>, in which he considers the potential impact of <i>Mayo</i> and <i>Myriad</i> on personalized medicine is particularly worth reading.<br><div class="MsoNormal">
<o:p></o:p></div>
<div class="MsoNormal">
<br></div>
<a href="http://pharmaceuticalpolicy.blogspot.com/2014/11/personalized-medicine-update.html#more">Read more »</a>Bob Bohrerhttp://www.blogger.com/profile/17081349778121412450noreply@blogger.com0tag:blogger.com,1999:blog-4025562924044932702.post-71953025501450294772014-10-16T19:20:00.003-07:002014-10-16T19:20:54.488-07:00What the Market Will Bear: Pricing Pressures and Pharmaceutical Value <div class="MsoNormal">
Until recently, the high prices of drugs seemed to be something
like the weather—something people complained a lot about, but about which
nothing could be done. That may be changing.<span style="mso-spacerun: yes;">
</span>I think the push-back on drug pricing is reaching new levels and both
the pharmaceutical industry and its chief lobbying group, PhRMA, are showing
concern and taking action.<span style="mso-spacerun: yes;"> </span>Examples of
the pushback on pricing can be seen in this <a href="http://www.cbs.com/shows/60_minutes/video/91X6DBwavaTeEas_ULJ2QSv79KL0jpSI/the-cost-of-cancer-drugs/">CBS
60 Minutes clip</a> and in <a href="http://www.foxnews.com/health/2014/10/11/fda-approves-hepatitis-c-drug-that-costs-1125-per-pill/">this
article</a> on Gilead’s pricing of its newer-than-Sovaldi combination Hep C
drug Harvoni. <span style="mso-spacerun: yes;"> </span>The level to which this
rising criticism of drug prices is causing PhRMA to be seriously concerned can
be seen in <a href="http://www.phrma.org/catalyst/what-60-minutes-failed-to-tell-you-about-the-value-and-cost-of-cancer-medicines">its
post-60 Minutes statement</a> and in <a href="http://www.phrma.org//catalyst/the-best-kind-of-progress-cancer-medicines-and-the-value-they-bring-to-us-all?utm_source=PhRMA+e-news&utm_campaign=b6f6a5366e-Update_from_PhRMA_10_05_2014&utm_medium=email&utm_term=0_4a09d8e2e7-b6f6a5366e-51426501&ct=t(Update_from_PhRMA_10_05_2014)">this
video <span style="mso-spacerun: yes;"> </span>and accompanying text about treatments
for cancer</a> and in <a href="http://www.phrma.org//catalyst/what-they-are-saying-about-the-value-of-new-innovative-medicines?utm_source=PhRMA+e-news&utm_campaign=b6f6a5366e-Update_from_PhRMA_10_05_2014&utm_medium=email&utm_term=0_4a09d8e2e7-b6f6a5366e-51426501&ct=t(Update_from_PhRMA_10_05_2014)">this
shot across the bow of critics of drug prices</a>.<span style="mso-spacerun: yes;"> </span>PhRMA is even <a href="http://blogs.wsj.com/pharmalot/2014/10/09/pharma-sues-again-over-orphan-drug-discounts-to-hospitals/">suing
the U.S. Department of Health and Human Services</a> over a rule that requires Orphan
Drugs that also have non-Orphan Drug uses that are priced at a discount, to be
sold the discount price even when a hospital uses the drug for the Orphan use. I
will address this PhRMA Orphan Drug suit in a future post.<span style="mso-spacerun: yes;"> </span>The pharmaceutical industry lobbying group is
clearly pulling out all the stops to make the case that pharmaceutical R&D
is a very costly enterprise and that expensive drugs are well worth their high
prices because of the health benefits they provide.<o:p></o:p></div>
<div class="MsoNormal">
<o:p><a href="https://drive.google.com/file/d/0BxIAusggav4bMnBFSm5YNVJjOEE/view?usp=sharing"> Download PDF</a></o:p></div>
<a href="http://pharmaceuticalpolicy.blogspot.com/2014/10/what-market-will-bear-pricing-pressures.html#more">Read more »</a>Bob Bohrerhttp://www.blogger.com/profile/17081349778121412450noreply@blogger.com0tag:blogger.com,1999:blog-4025562924044932702.post-13495765859265405602014-10-03T13:32:00.000-07:002014-10-03T13:32:16.435-07:00Cancer Drugs, Survival, Research Priorities, and the Human Condition<div class="MsoNormal" style="margin-left: -4.5pt;">
<span style="font-family: Geneva; mso-fareast-language: JA;">It is fundamental to human nature to hope, and one
manifestation of this aspect of human nature is the desperate but
understandable desire of cancer patients with very grave prognoses to look for
a glimmering possibility of beating the odds. In this post I will look closely
at the data on an anti-cancer antibody may have incrementally raised the bar in
the treatment of one particularly grave cancer and discuss how this and other
similar cancer drug development fits within the current framework of healthcare
delivery and reimbursement.<span style="mso-spacerun: yes;"> </span><o:p></o:p></span></div>
<div class="MsoNormal" style="margin-left: -4.5pt;">
<span style="font-family: Geneva; mso-fareast-language: JA;"><o:p></o:p></span></div>
<a href="http://pharmaceuticalpolicy.blogspot.com/2014/10/cancer-drugs-survival-research.html#more">Read more »</a>Bob Bohrerhttp://www.blogger.com/profile/17081349778121412450noreply@blogger.com0tag:blogger.com,1999:blog-4025562924044932702.post-59142637222072504372014-09-24T15:52:00.000-07:002014-09-24T15:52:02.907-07:00Two Congressmen Express Concern About the FDA's Proposed Changes to the Labeling Requirements for Generic Drugs
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My first two posts on this blog were about the FDA’s
proposed change to the <a href="http://pharmaceuticalpolicy.blogspot.com/2014/02/the-fdas-proposed-rule-changes-for.html">rules
for generic drug labels</a> and an <a href="http://pharmaceuticalpolicy.blogspot.com/2014/03/an-estimate-of-pharmaceutical-industry_14.html">estimate
of the liability costs</a> that might be incurred by the generic drug industry
as a result of the proposed change.<span style="mso-spacerun: yes;"> </span>The
Generic Pharmaceutical Manufactuer’s Association lobbying efforts appear to
have motivated Congressmen Steve Israel (D-NY) and Timothy Bishop (D-NY) to
draft a letter to the FDA requesting changes to the proposed rule.<span style="mso-spacerun: yes;"> </span>A copy of the Congressmen’s letter to the FDA
can be downloaded through <a href="https://drive.google.com/file/d/0BxIAusggav4bX2NFeEV3dmpueGs/edit?usp=sharing">this
link</a>.<o:p></o:p></div>
Bob Bohrerhttp://www.blogger.com/profile/17081349778121412450noreply@blogger.com0