Los Angeles, California-based Puma Biotechnology has shuffled a challenging new drug application (NDA) onto FDA’s desk.
Neratinib has polarized experts and investors over the last few weeks, with its data flaws and dubious benefit-to-risk ratio. The drug is currently under review for use in breast cancer patients who have had their tumors surgically removed.
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On Wednesday, FDA’s Oncologic Drugs Advisory Committee voted 12-4 in favor of recommending the tyrosine kinase inhibitor be approved. But the endorsements were far from emphatic and many doubts still swirl. FDA typically – but not always – follows the recommendations of its advisory committees.
The issue at hand: thousands of patients that take the drug won’t benefit. It’s prophylactic. Their cancer wouldn’t have returned either way. In a pivotal two-year study, 8.1 percent of patients in the control group saw their cancer return. That compares to a 5.8 percent rate of recurrence in the cohort taking neratinib (2.3 percent less).
On the other hand, nearly all patients experienced side effects, primarily diarrhea. In one study 96 percent had some degree of diarrhea and 40 percent of patients had Grade 3 diarrhea, which “may require treatment in the hospital or clinic.” Grade 4 is deemed life-threatening.
FDA noted in a review on Monday that this impacted use of the drug. “The tolerability of neratinib in this patient population is a concern given the frequent dose interruptions, reductions and discontinuations observed, mostly due to diarrhea.”
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If patients can’t stomach the drug, is it worth bringing to the market?
Puma got to work defending the safety and tolerability profile of neratinib in Wednesday’s FDA advisory committee meeting.
According to Susan Moran, Puma’s VP of clinical development, 16 percent of patients discontinued due to diarrhea and 28 percent had a dose reduction. However, she also stressed that the side effects were short-lived, primarily impacting patients in the first eight days of treatment.
“It occurs early, is generally of short duration, and infrequently leads to complications leading to hospitalization,” Moran told the committee.
Investors, on the other hand, may be near the point of nausea watching Puma’s shares rollercoaster up and down. In 2014, they reached a peak of $238/share. Then it all went downhill. Beyond the drug’s side effects, Puma made a series of changes to the trial design, compromising the quality of the data. So much so, that FDA recommended the company delay its NDA. It forged ahead, regardless.
Puma may be rewarded for the bold move.
Following Monday’s better-than-expected FDA review meeting, Puma shares closed the day up 40 percent. Going into Wednesday’s advisory committee meeting, they stood at $69.25. A hold on trading was then put into effect pending the panel’s vote.
Puma shares shot up 29 percent once the hold was lifted. A 12-4 vote in favor of the drug is a good outcome from an FDA advisory committee, after all. Even if many observers still have doubts.
The ball is now in FDA’s court.
Photo: marrio31, Getty Images
