Puma Biotechnology (PBYI) shares fell Monday on the surprise disclosure that two drugs, not just one, may be necessary to prevent serious diarrhea from afflicting breast cancer patients treated with its experimental drug neratinib.
A marketing application for neratinib to treat breast cancer is under review by the U.S. Food and Drug Administration. Monday's disclosure that Puma is adding a second drug to its diarrhea prophylaxis protocol for neratinib-treated patients once again raises concern that the drug is too toxic to be approved.
Puma shares fell 27% to $36.85 Monday after a research abstract outlining new neratinib diarrhea safety data was posted in advance of a breast cancer research meeting being held in December.
The abstract describes results from a clinical trial in which Puma is using preventative dosing of the anti-diarrheal medicine loperamide to lower the incidence of serious diarrhea reported in neratinib-treated breast cancer patients. The abstract, however, also discloses a new anti-diarrheal regimen consisting of loperamide and budesonide, a steroid.
Investors reacted negatively to the addition of budesonide because it suggests loperamide alone isn't working well enough.
The rate of grade 3 diarrhea was 27% in neratinib-treated breast cancer patients treated with preventative doses of loperamide. When loperamide and budesonide were used together, the rate of grade 3 diarrhea fell to 12.5%, according to the research abstract.
Grade 3 diarrhea is defined as an increase of seven or more stools per day plus incontinence. Without any preventative treatment, 40% of neratinib-treated breast cancer patients experience grade 3 diarrhea or higher.