The U.S. Food and Drug Administration this morning released addi­tional in­­for­ma­tion related to its Oncologic Drugs Advisory Committee meeting scheduled for this Wednesday, when the committee will review data related to the application by Onyx Pharmaceuticals (NASDAQ:ONXX) to have car­filz­o­mib approved as a new treat­ment for multiple myeloma.

In addi­tion to a draft agenda ^[1] and draft committee roster ^[2], the Food and Drug Administration (FDA) released briefing in­­for­ma­tion for the committee members and a question about the risk/benefit profile of carfilzomib ^[3] (Kyprolis ^[4]) that the advisory committee will discuss and vote on at the meeting.

The FDA briefing document and question for the committee can be useful in gauging internal FDA sentiment in regard to car­filz­o­mib's new drug application.

(For an overview of the key briefing document prepared by the FDA staff for Wednesday's meeting, see this ^[5] Beacon news article.)

Last September, Onyx Pharmaceuticals completed its application to the FDA to have car­filz­o­mib approved for the treat­ment of re­lapsed and refractory (resistant) multiple myeloma patients who have had at least two prior ther­a­pies (see related Beacon ^[6] news).

To assist it with its decision, the FDA has scheduled Wednesday’s meeting of the Oncologic Drugs Advisory Committee (ODAC).  The ODAC is the advisory committee that advises the FDA regarding cancer drugs.

The FDA is expected to make a decision about car­filz­o­mib’s application by July 27.

Draft Question

Included among the documents the FDA released this morning is a draft of the question ^[7] the advisory committee will vote on at the end of this Wednesday’s meeting.

The question is:  "Is the risk benefit assess­ment favorable for the use of car­filz­o­mib in the treat­ment of patients with re­lapsed and refractory multiple myeloma who have received at least two prior lines of ther­apy that included a proteasome inhibitor and an immuno­modu­la­tory agent?"

The final version of the question that the FDA will ask the advisory committee on Wednesday will likely include a bullet point summary of the risk/benefit profile for car­filz­o­mib.  The committee will specifically consider these bullet points when voting whether car­filz­o­mib has dem­onstrated a favorable risk/benefit profile.

Briefing Information

Two sets of briefing in­­for­ma­tion for Wednesday's afternoon car­filz­o­mib session were released this morning.

The first is an extensive FDA staff review of the car­filz­o­mib drug application (main document ^[8] and errata ^[9]).  Besides providing back­ground in­­for­ma­tion about multiple myeloma, the document states the specific patient population for which the FDA is considering approving car­filz­o­mib, summarizes car­filz­o­mib’s efficacy and safety data, and describes the issues the FDA has with the car­filz­o­mib application.

The FDA briefing in­­for­ma­tion along with the wording of the question the FDA will ask the advisory committee to vote on are important.  They provide insight into which way the FDA is leaning in regard to whether or not to approve car­filz­o­mib.

Because Onyx submitted the car­filz­o­mib application through what is known as an “accelerated approval process,” the application is based on Phase 2 data from the “003-A1” trial.  Normally, the FDA requires new drug applications to be based on data from more extensive Phase 3 clinical trials.

The FDA briefing in­­for­ma­tion therefore focuses on results from the 003-A1 trial, which studied single-agent car­filz­o­mib in re­lapsed/refractory myeloma patients.

In addi­tion to the internal FDA review of car­filz­o­mib's new drug application, the FDA this morning also released a briefing document ^[10] prepared by Onyx Pharmaceuticals, the com­pany developing car­filz­o­mib.

Draft Agenda

The advisory committee will be discussing two drugs during Wednesday’s meeting.  Carfilzomib will be discussed during the afternoon session.

After opening remarks and introduction of the committee, Onyx will give several presentations.  The presentations will likely explain why car­filz­o­mib addresses an important unmet treat­ment need, summarize the Phase 2 003-A1 trial results, and describe future clinical trials that are underway or planned to con­firm car­filz­o­mib’s efficacy and safety in myeloma patients.

The FDA staff will also make a presentation stating which agency employees are responsible for reviewing car­filz­o­mib’s application and what require­ments the application must meet in order to be approved.  The FDA presentation will also likely summarize the 003-A1 clinical trial results and describe any ongoing and future clinical trials.  The presentation will conclude with the issues the agency would like the advisory committee to discuss.

After the committee is given a chance to ask any questions they may have about the presentations, the public will be given the opportunity to address the advisory committee.  This is a time when patients, advocacy organizations, or others with an interest in whether the drug gets approved can present their comments.

The committee members will then discuss the question the FDA has asked them to vote on.  The meeting will then conclude with the committee’s vote.

The committee's vote can be expected to play a role in the FDA's decision regarding car­filz­o­mib's new drug application.  However, the FDA is not legally bound to make decisions on new drug applications that are in agreement with the advice it receives from its advisory committees.

Additional Details And Assessment Of The FDA Documents

This news update provides an initial overview and summary of the documents released by the FDA this morning.  The Beacon will be analyzing the documents in more detail as the morning progresses, and will publish a follow-up article as soon as that analysis is completed.

Update (June 18, 2012 - 12:30 p.m.) - The Beacon's analysis of the FDA staff's briefing document for Wednesday's meeting can be found here ^[5].