Preparing an anticipatory Risk Evaluation and Mitigation Strategy and receiving the blessing of an FDA advisory panel may not be enough to gain approval on the first try for a drug with significant risks.

That's what Bristol-Myers Squibb found out, when FDA sent it a "complete response" letter for belatacept for the proposed indication of preventing kidney transplant rejection. The drug also is being studied for the prevention of liver transplant rejection.

The letter "requests the 36-month data from the ongoing Phase III studies to further evaluate the long-term effect of belatacept," the company said in a statement May 1, adding that the agency also wants additional information on the proposed REMS and manufacturing issues.

The Cardiovascular and Renal Drugs Advisory Committee voted 13-5 in favor of approving the drug on March 1, with the REMS playing a key role in the favorable outcome, as members felt the drug's safety issues required post-marketing studies (Also see "Bristol's Belatacept Gets Wary Green Light From FDA Advisory Panel" - Pink Sheet, 1 March, 2010.).

It is unclear at what stage in the development process BMS created the REMS, but FDA appears to need more time to assess how it could impact the safety issues related to the drug. The foremost risks of the drug are post-transplant lymphoproliferative disorder, which is associated with significant mortality, and progressive multifocal leukoencephalopathy, a neurological condition that also can be fatal (Also see "Bristol Hopes REMS Proposal Can Overcome Safety Concerns About Belatacept" - Pink Sheet, 25 February, 2010.).

If FDA approves the drug with a REMS, it could give BMS an edge in the field, since other immunosuppressive drugs such as Roche's CellCept (mycophenolate mofetil) also carry risks of PML and other serious conditions on their labels but were approved before the REMS era began in 2008. The firm might be able to argue that it has similar risks, but better controls, than competing products.

BMS declined to comment on when it expects to respond to the "complete response" letter or on whether the new data from the clinical trials might lead it to alter the design of the proposed REMS, which consists of a communication plan and a Medication Guide.

The 36-month data might be ready this fall. BMS submitted the 24-month data from the Phase III studies as part of the BLA, which FDA accepted on Sept. 3, 2009. Database lock on the 24-month data occurred in March 2009, with a late-breaking safety update report covering events that occurred up until June or July, according to a briefing document FDA prepared for the advisory committee meeting.

-Martin Berman-Gorvine (m.berman-gorvine@elsevier.com)

When A REMS Is Not Enough: BMS Needs More Safety Data For Belatacept

More from Archive

More from Pink Sheet