Shares in Puma Biotechnology jumped 40% after the FDA trod lightly around doubts about its filing for approval of breast cancer drug neratinib. But the talking points raised ahead of Wednesday’s advisory committee meeting leave Puma open to a grilling over its trial modifications, neratinib’s side effect profile and its choice of population.
The reaction of the stock, which shot up 80% before falling to close up 39%, reflects the mix of top-line positives and lingering uncertainties presented in the FDA briefing document. A summary of the text states that despite “unplanned amendments and potential uncertainty introduced with respect to the magnitude of neratinib effect” the FDA reviewers think the data support “an effect of neratinib.”
That suggests changes to the size, duration, analysis and population of the clinical trial haven’t totally tarnished the data in the eyes of the FDA. What is less clear is whether the experts tasked with reviewing the filing on Wednesday will share this position.
The briefing document gives the panel plenty of reasons to take a dim view of the application for approval of the kinase inhibitor. The FDA itself was more downbeat about the study when it held a pre-NDA meeting with Puma in March 2016. Officials advised Puma against filing for approval “due to several study conduct issues.” The FDA said these issues would make “interpretation of the results problematic.”
In a conference call with investors at the end of that month, Auerbach said “the FDA did not raise any objections to Puma filing with the two-year invasive disease-free survival data,” according to OncLive. Puma went ahead and filed its NDA four months later.
The panel’s view on the significance of the study conduct is one of several potential stumbling blocks for Puma.
Management must also allay doubts about whether it is appropriate to approve a drug that appears to deliver a small benefit and significant side effects for use in patients who have had their cancer removed surgically. Puma envisages neratinib being used to reduce the risk of cancer recurring. As the FDA notes in its briefing document, prior approvals of such adjuvant therapies have all been for drugs already cleared for use in the metastatic setting.
Given 40% of patients in the neratinib arm of the trial suffered serious diarrhea—compared to 2% in the placebo cohort—and the difference in invasive disease-free survival between the two arms was a small but statistically significant 2.3%, it is questionable whether the risk-benefit profile is favorable for patients who are healthy but at risk of cancer recurrence.
The advisory committee will discuss these topics at a half-day meeting on Wednesday.