Two Congressmen Express Concern About the FDA's Proposed Changes to the Labeling Requirements for Generic Drugs

My first two posts on this blog were about the FDA’s proposed change to the rules for generic drug labels and an estimate of the liability costs that might be incurred by the generic drug industry as a result of the proposed change.  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.  A copy of the Congressmen’s letter to the FDA can be downloaded through this link.

More on Anti-CD20 Antibodies for Leukemia: The FDA and TG Therapeutics Reach Agreement on Phase III Trial Design

In my post of June 2, 2014, I questioned the significance of data that were hailed as evidence of the superiority of Gazyva, a new anti-CD20 antibody for the treatment of chronic lymphocytic leukemia (CLL) as compared with Rituxan, the original anti-CD20 antibody used to treat CLL.  In that post, I focused on the difficulty of meaningful conclusions about the comparative efficacy of two drugs, even when those drugs are studied head-to-head, when the two drugs were administered at very different doses.  Here is news on the development of another anti-CD20 antibody for the same indication, with the likely result being even more debate about the comparative effectiveness of these agents and the continuing absence of studies that would definitively answer the question.

See the Onclive story on the FDA and TG Therapeutics see http://www.onclive.com/web-exclusives/FDA-Grants-Special-Protocol-Assessment-to-Phase-III-UblituximabIbrutinib-Studyhttp://www.onclive.com/web-exclusives/FDA-Grants-Special-Protocol-Assessment-to-Phase-III-UblituximabIbrutinib-Study

Biosimilars And Gene Patents In This Week's News

According to a story by Bronwyn Mixter in this week’s Bloomberg’s BNA BioTech Watch, the FDA has received at least twenty-five IND’s for biosimilar development programs.  Some quick perspective on that is appropriate.  Twenty-five initial IND’s for the development of new small molecule drugs for cancer or autoimmune disease would face many years of clinical trials and long odds against approval (DiMasi et al estimated the approval rate at sixteen percent to nineteen percent).  However in this “a little brave” and “a little new” world of biosimilar development, clinical development programs are likely to be much shorter in duration than development programs for new drugs or innovator biologics, and the success rates are likely to be very high, as I indicated in my post of May 19^th, 2014.  The DiMasi study referenced above estimated the large molecule success rate at thirty-two percent; and, biosimilars are not only within that large molecule category, they are copies of drugs that have already been shown to be reasonably safe and effective.  So it is very likely that we will see filings for the approval of more than twenty biosimilars in the next three years.  It will be very interesting to watch the development of the biosimilar marketplace.

Novartis Hopes PARADIGM-HF Study Results Lead to Blockbuster Sales for Its LCZ696: Big Diseases and Pharmacoeconomics

In this week’s New England Journal of Medicine the most widely publicized article reported on the findings of the PARADIGM-HF study, which tested Novartis’s experimental drug LCZ696 against enalapril, a commonly used ACE inhibitor, in the treatment of heart failure (HF). The double-blind study randomized over 8,442 patients with moderate to severe HF to a regimen of the experimental drug plus standard therapy or of enalapril plus standard therapy.  The primary outcome was a composite of deaths from cardiovascular disease and first hospitalizations for HF. After 27 months, the trial was halted because an interim analysis showed a very large benefit for the experimental drug group. The LCZ696 patients had an approximately 20 percent reduction in the primary outcome (914 patients versus 1,117 patients in the enalapril group: “hazard ratio in the LCZ696 group, 0.80; 95% confidence interval [CI], 0.73 to 0.87; P<0.001”).  The experimental drug group also had comparably substantial and significant reductions in the risk of death from any cause and the risk of death from cardiovascular disease.  The results of the study have been reported on widely and it is clear that Novartis hopes LCZ696 will achieve blockbuster revenues.  For purposes of this post, I would like to focus on two of the study’s findings with obvious pharmacoeconomic ramifications for calculating the drug’s costs and benefits, which are the reductions in both hospitalizations and in deaths:

Over the duration of the trial, the numbers of patients who would need to have been treated to prevent one primary event and one death from cardiovascular causes were 21 and 32, respectively.

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