Puma Biotech Crashes After Diarrhea Risk is Linked to Breast Cancer Drug in Abstract

November 15, 2016
By Alex Keown, BioSpace.com Breaking News Staff

LOS ANGELES – Shares of Puma Biotechnology plummeted Monday after the company disclosed patients taking its experimental breast cancer drug, Neratinib, may require a second drug to prevent serious diarrhea.

In an abstract for the 2016 San Antonio Breast Cancer Symposium in December, Puma said it was using the anti-diarrheal medicine loperamide for patients using Neratinib, as well as the addition of the steroid budesonide. According to the abstract, incidents of grade 3 diarrhea rose from 16 percent to 27 percent in the Phase II study of neratinib combined with prophylactic loperamide.

The Street’s Adam Feuerstein said the addition of a second anti-diarrhea medication raises concern that neratinib is “too toxic to be approved.” Neratinib is a potent irreversible tyrosine kinase inhibitor for treatment of HER2-positive breast cancer. Puma submitted its New Drug Application for neratinib to the U.S. Food and Drug Administration in July. The NDA was submitted following a successful Phase III trial that demonstrated treatment with neratinib resulted in a 33 percent reduction of risk of invasive disease recurrence or death versus placebo.

Shares plunged more than 20 percent Monday, from $50.95 to a low of $36.70, before rallying to a close of $40.10. The morning shares are up more than 5 percent after analysts at Credit Suisse said the “pullback is overdone.” Analyst Kennen MacKay , as reported by Benzinga, listed several reasons that investors should not be overly concerned, including the note that 60 percent of patients experiencing grade 3 diarrhea were “non-compliant with scheduled loperamide.” Also, incidents of grade 3 diarrhea were single-episode events, with episodes restricted to the first cycle of therapy.

Diarrhea has long been associated with chemotherapy due to the effect the drug has on healthy cells in the digestive tract. Grade 3 diarrhea is defined as an “increase of seven stools per day, plus incontinence.”

“A structured loperamide prophylactic regimen for two cycles is associated with a lower incidence and severity of neratinib associated diarrhea, with notably less grade 2/3 diarrhea compared to ExteNET events. There appears to be some adaptation to the effects of neratinib, as higher-grade diarrhea occurs early and does not typically recur. Preliminary data suggest that adding budesonide may further improve outcomes; enrollment into the budesonide cohort continues,” Puma said in the conclusion to its abstract.

Credit Suisse, Benzinga reported, continues to see potential for the approval of neratinib. Not only that, but the analysts expect neratinib to be used “in HER2 positive patients who also have HR+, where neratinib has shown outsized benefit.”