Monday, June 26, 2017

BIO 2017: Part I ––Virtual Development Is A Reality.

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.

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 Remicade/ infliximab. 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.  The FDA has already granted Pfizer approval to market Inflectra, a biosimilar Remicade (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? 

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
(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.

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.  I’ll discuss the risk of failure, infringement, and marketing issues in Part II of Virtual Development.

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