Bristol Melanoma Drug's Advisory Panel Delayed Following Review Date Delay

Additional Phase III data for ipilimumab might be available by next year, and an early March advisory committee date now looks likely, given the rescheduled PDUFA date of March 26, 2011.

FDA's advisory committee calendar has caught up with its review schedule for Bristol-Myers Squibb's melanoma drug Yervoy (ipilimumab), with the planned panel meeting being postponed to an unspecified date following a three-month extension in the user fee target date.

FDA's Oncology Drugs Advisory Committee was to have considered Bristol's BLA for the anti-CTLA-4 monoclonal antibody, which is intended for second-line melanoma treatment, on Dec. 2 (Also see "Advisory Committee Review Will Test Whether One Trial Will Do The Trick For Bristol's Ipilimumab" - Pink Sheet, 18 Oct, 2010.).

Bristol said FDA told it earlier this month that it needs more time to review the BLA and has therefore moved the PDUFA review date from Dec. 25 to March 26, 2011. The reason the company gave for the delay is that the agency has asked it for "further analysis of data pertaining to the current application for pre-treated advanced melanoma and the agency considers this to be a major amendment to the drug's BLA."

"It's not uncommon for the agency to ask additional questions as part of the review process for a new drug application, particularly when the drug has a novel mechanism of action," the company added in an e-mail. "Bristol-Myers Squibb has provided the FDA with further analysis of data that was included in the original submission, which will help the agency better characterize the profile of ipilimumab."

Significant Efficacy, Significant Toxicity

Bristol submitted the BLA based on a single pivotal Phase III trial in July, and it was accepted for priority review, which normally means a six-month review schedule (Also see "BMS Files Ipilimumab With FDA And EMA, Positioning It For Launch Next Year" - Pink Sheet, 22 Jul, 2010.). Ipilimumab already is being made available through an expanded access program.

However, another Phase III study is underway, and results may be available by the time the advisory committee meets to consider the drug and FDA makes its decision. "The ongoing Phase III trial in first-line metastatic melanoma is event driven, so it is difficult to project a precise timeline for completion, but we anticipate results early next year," the company said.

The completed study tested a 3 mg/kg dose of ipilimumab plus Bristol's experimental gp100 vaccine (403 patients) against monotherapy with ipilimumab and placebo (n=137), and the gp100 vaccine with placebo (n=136). Median overall survival was 10.1 months for patients who received ipilimumab alone, 10 months for those on ipilimumab plus the gp100 vaccine, and only 6.4 months for those who got the vaccine without the drug. But there were serious safety problems due to the toxicity of the drug, with 14 treatment-related deaths in the study, or 2% of the study population, half of them immune-related.

Although the ipilimumab panel is being postponed, ODAC will still be reviewing iPR Pharmaceuticals/AstraZeneca's Zictifa (vandetanib) for unresectable (non-operable) locally advanced or metastatic medullary thyroid cancer, as scheduled (Also see "Advisory Panel To Consider Vandetanib's New Life In Niche Thyroid Cancer" - Pink Sheet, 20 Oct, 2010.).

-Martin Berman-Gorvine ( [email protected] )