“The FDA approved telotristat ethyl tablets for use in combination with somatostatin analog therapy for the treatment of adults with carcinoid syndrome diarrhea.
“The approval is intended for patients with carcinoid syndrome — a rare and debilitating condition that affects people with carcinoid tumors and metastatic neuroendocrine tumors — that somatostatin analog therapy alone inadequately controlled. Carcinoid syndrome occurs in less than 10% of patients with carcinoid tumors. The tumors cause the excess release of the hormone serotonin, resulting in diarrhea, which in turn can lead to weight loss, malnutrition, dehydration and electrolyte imbalance.”
“The benefit for breast cancer patients treated with Puma’s neratinib was ‘awfully small’ for a drug that causes ‘a lot of diarrhea,’ said Dr. Harold Burstein, a breast cancer expert from the Dana-Farber Cancer Institute.
“Puma shares are down more than 9% to $177.04 in Monday trading.
“Burstein spoke to me following presentation of results from the neratinib phase III ‘ExteNet’ study at the American Society of Clinical Oncology (ASCO) annual meeting Monday. Puma is developing neratinib for the treatment of HER2-positive breast cancer patients in the extended adjuvant setting.
“The absolute disease-free survival for neratinib was 93.9% compared to 91.6% for placebo — a difference of 2.3 percentage points. The benefit, while statistically significant, is tough to call clinically meaningful for breast cancer patients given the drug’s toxicity, Burstein said.
“Forty percent of patients treated with neratinib experienced grade 3 diarrhea, which is defined as seven more stools per day, incontinence and hospitalization.
” ‘This is not someone simply eating too many chili peppers and having a single bout of diarrhea,’ said Burstein.”
“Puma Biotechnology, Inc. PBYI, +2.74% a development stage biopharmaceutical company, announced the initiation of a Phase II trial of Puma’s investigational drug PB272 (neratinib) for the extended adjuvant treatment of breast cancer.
“The 70 patient study will be an open label single arm Phase II trial of PB272 monotherapy administered to patients with HER2-positive early stage breast cancer who have previously received adjuvant treatment with trastuzumab. Patients will receive extended adjuvant treatment with neratinib for a period of one year. Patients will receive primary prophylaxis with high dose loperamide (16 mg per day initially) in order to attempt to reduce the neratinib-related diarrhea. The primary endpoint of the trial is reduction in the incidence and severity of diarrhea.
“ ‘We are pleased to initiate this Phase II trial,’ said Alan H. Auerbach, Chief Executive Officer and President. ‘Because the ExteNET Phase III trial was run prior to the implementation of loperamide prophylaxis in clinical trials of neratinib, in the ExteNET Phase III trial neratinib was administered without loperamide prophylaxis. The results from this Phase II study will give us a better understanding of the safety of neratinib in the extended adjuvant setting with concurrent high dose loperamide administered and, importantly, to what degree the grade 3 neratinib-related diarrhea can be reduced. We anticipate that initial results from this trial should be available by yearend 2015 and would enable us to include this data in our NDA filing for neratinib in the extended adjuvant setting, which is currently anticipated for the first quarter of 2016.’ “