Despite some safety concerns such as severe diarrhea, the U.S. Food and Drug Administration approved Puma Biotechnology’s breast cancer drug Nerlynx (neratinib) in July 2017. Those same safety concerns though appear to be a roadblock in gaining marketing approval from the European Medicines Agency.
On Thursday, Puma announced the Committee for Medicinal Products for Human Use (CHMP) of the EMA "communicated a negative trend vote" over potential approval of neratanib in the European Union. The negative trend vote from the CHMP will likely mean the EMA will not authorize neratanib for extended adjuvant treatment of early-stage HER2-positive breast cancer. To gain approval, the company will likely be asked to submit more data. The EMA is set to make a decision next month.
That news sent shares of Puma Biotechnology tumbling overnight. Shares fell more than 25 percent to $67.40 in pre-market trading. The stock closed at $90.90 on Tuesday.
In its Tuesday announcement, Puma said CHMP was of the opinion that the "benefit-risk assessment is negative as the study results are based on evidence from a single pivotal trial and the 2- and 5-year invasive disease-free survival (iDFS) benefits observed to-date may lack sufficient clinical relevance."
CHMP’s opinion was based on the results from both the Phase III ExteNET trial in extended adjuvant early-stage HER2-positive breast cancer and the Phase II CONTROL trial in extended adjuvant early-stage HER2-positive breast cancer. The Phase III ExteNET data was the same provided to the FDA. Trial data showed treatment with Nerlynx resulted in a 33 percent reduction of risk of invasive disease recurrence or death versus placebo. During clinical trials, Nerlynx, a potent tyrosine kinase inhibitor, demonstrated a disease-free survival (DFS) rate of 94.2 percent compared with 91.6 percent in the placebo group.
Earlier this month, Puma leadership met with the CHMP scientific advisory group on oncology to discuss potential labeling of neratanib in Europe should the drug gain approval. In a filing with the U.S. Securities and Exchange Commission, Puma said based on feedback from that meeting it would "modify the summary of product characteristics" or the product label in its Marketing Authorization Application to "further refine the intended population to patients at a high risk of disease recurrence."
When neratanib was before an FDA advisory committee last year, members were split over the safety concerns. During clinical trials, approximately 40 percent of patients who took the drug suffered a severe form of diarrhea, although about 95 percent of patients who took the drug had some form of diarrhea. Incidents of grade 3 diarrhea were single-episode events, with episodes restricted to the first cycle of therapy. That FDA committee ultimately passed the drug in a 12-4 vote and then the full FDA supported approval in order to provide patients with an option to keep the breast cancer from returning. Extended adjuvant treatment for breast cancer is important, as about one-third of people treated with a drug like Roche's Herceptin and chemotherapy may eventually see their cancer return. This is the first extended adjuvant therapy of its kind approved by the FDA.
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