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Carfilzomib at the ODAC Hearing

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By Jim Omel, MD

All of us with myeloma were thrilled to get a resounding 11-0-1 vote in favor of carfilzomib at the FDA's Oncologic Drugs Advisory Committee (ODAC) meeting on Wednesday, June 20.  Prior to the meeting, the general mood was neutral at best for carfilzomib's chances, and many financial analysts even predicted a negative outcome.  The FDA had identified significant cardiac, pulmonary, and liver toxicities with the drug and clearly stated their doubts about carfilzomib's Risk-Benefit ratio in their briefing document.

When the FDA has strong sentiment for a new drug's approval they say so.  When they have doubts however, the agency calls in a panel of outside experts for advice.  ODAC is a standing FDA committee of 13 oncologists and biostatisticians, very few of which treat myeloma patients.  For every new drug application with an identified cancer indication, the committee also selects a patient representative (PR) with that specific cancer to join the committee for that meeting.  The FDA PR program involves about 125 individuals with a huge spectrum of first-hand disease experience.  There are two to three of us with myeloma who are PRs, and I was the one selected to represent our disease last Wednesday.

The meeting began with a presentation by Onyx Pharmaceuticals of their phase II trial results for relapsed and refractory myeloma patients and FDA official's enumeration of their significant concerns.  Committee members then asked pointed questions of the sponsor (Onyx), the tone of which sounded very negative.  Most of us in the room frankly had a sense that the drug would not be approved based on the sharp tenor and tone of the questions.  I badly wanted to comment on the drug's good qualities, but strict committee protocol only allowed sponsor questions at that point.

Following a scheduled break, nine members of the public were each allowed three minutes to comment on the value (or not) of the drug.  People from the DC area, the MMRF, and the IMF truly ruled the day and gave new breath to carfilzomib. From the IMF, Michael and Robin Tuohy and Diane Moran made exceptionally eloquent statements. The committee of breast cancer, prostate cancer, and childhood cancer experts saw firsthand that myeloma is NOT a disease of old peopleand other "typicals" they had been taught in residency.  From my vantage point at the table I watched them INTENTLY listen to all 9 speakers.  No one surreptitiously checked their cell phones, fidgeted with their ties, or yawned as if to say, "I've heard these meaningless anecdotal testimonials before."  They were mesmerized!

The formal meeting schedule finally allowed comments from panel members.  I quickly got the chairman's eye and indicated my desire to speak.  As he jotted my name I prepared my thoughts and waited my turn.  I used Dr. Durie's words and said that myeloma is "a sneaky disease."  When it appears to be stopped, its genetic expression changes and myeloma cells escape death (apoptosis) by utilizing metabolic "escape pathways."  Myeloma physicians need multiple drugs (like carfilzomib) to block multiple pathways to control this cancer.  Though carfilzomib will not cure myeloma, it will buy precious time to stay alive until research finally gives us a cure.  I made other comments which countered a panelist's earlier assertion that "only the best patients were pre-selected by this phase II trial by living 5 years."  I reminded him that many of us now live 5 years because of treatments developed since 2000.  I also pointed out that 85% of myeloma patients present with "standard risk" genetic profiles and 15% are classified as "high risk."  In the Onyx trial, fully 28% of the patients had high-risk cytogenetics.

Discussion around the table had a decidedly different tone after the 9 powerful public speakers, and I had great hope for a vote of approval.  Topics centered on the fact that various toxicities identified by the FDA would be expected in the heavily pre-treated patients of this trial.  When the time came we all cast our electric votes, and no one had access to anyone else's vote.   At last the tally appeared on the screen.  There it was:  11,0,1.  The one abstention was cast by a biostatistician who explained that he opposed trial design, not the drug.

A few of us shared broad smiles and later tight hugs.  The ODAC is only an advisory body and the FDA will make its own decision on approval or not.  By law (PDUFA) this decision must come by July 27 of this year.  I think the resounding 11-0 vote will heavily influence approval.  

Following the meeting, the FDA's official who organizes the PR program told me she "nearly cried" when the vote tally flashed on the screen and she considered the relief which all of us with myeloma felt.  Deb is a wonderful government official with warm humanity and empathy.

Next up is pomalidomide, an immunomodulatory drug (IMiD) with proven clinical activity in patients NOT responding to Revlimid� (lenalidomide).  It too is at the FDA right now awaiting approval based on a phase II trial.  A decision is not expected until late 2012 or early 2013.  I hope pomalidomide is so impressive that an ODAC evaluation will not even be necessary.  If it is however, bring it on!  Either I or another capable myeloma PR will gladly represent those of us with this horrible insidious cancer again.  With the IMF's help we WILL find a cure!

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7 Comments

I was riveted watching these proceedings live, and was so thankful to see Jim on ODAC. His comments as well as those from Robin, Michael and Diane filled me with pride. I yelled a big "YES" when the vote was posted, resulting in getting a somewhat strange look from my dog. Thank you all!

Hi Jim!

This is an excellent blog in painting the picture of the ODAC review. Your being on the committee was so beneficial to us all as your knowledge and passion as a myeloma patient and doctor were instrumental in helping the committee to see more clearly that more drugs are needed and that access is needed now. Patients and doctors clearly need to weigh out the benefit vs risk, but as patients, we are always faced with some risk. I loved your comment after the vote that you were not "squeamish" at all in your "YES" vote! Thank you!!

My husband Michael Morwitz has had myeloma since late 2007 and was diagnosed in early 2008. He has gone through 2 stem-cell transplants and had a long remission for about two years. He is currently on the Phase 2 Carfilzomib trial at Sloane Kettering under the supervision of Dr. Hani Hassoun, and has had amazingly good results which are evident in his declining numbers but also in his increased energy. We realize this is not a cure, but we feel extremely optimistic --both about carfilzomib and perhaps also pomalidomide should he become resistant. We also attribute his new-found confidence and energy to his excellent care and his doctor's responsiveness. Optimism seems to make a difference.

Thank you, Jim, for representing our interests and needs. You, as a physician and a patient, know the risks of NOT having options, as well as the proven risks of all of the options we have now. I greatly appreciate your contribution. I'm sure I speak for many, many people.

Jim,

Thank you and all the others who took the time to "fight the good fight" for Carfilzomib and through your personal testimonies were able to touch the hearts and minds of those on the committee. My husband, Rodney, was diagnosed with myeloma on Sept. 1, 2002. He has been blessed to be part of the Onyx Access Program or I believe he would not be here today. I continue to pray that the FDA will approve this chemo-therapy and that many lives will be prolonged because of the amazing efforts of the International Myeloma Institute and so many others! Way to go! How sweet the victory!

I'm a phsician, as well as a patient, and I'd be willing to serve as a mm PR. It might be that my fifty years in practice as a psychiatrist would bring a different point of view to these proceedings.
I am doing some special CME on research statistics at The Roal College of Physicians and Surgeons of Canada this month.
Regards,
Harold A. Hamer, M.D.

Thanks everyone for your comments. Serving on the ODAC was a rewarding experience, and seeing the committee's riveted response to Michael, Robin, and the other 7 speakers was exciting. Harold, thank you for your offer to serve as an FDA PR. IF you are willing to complete at least a dozen FDA forms (some notarized), your personal financial data, required education, yearly update courses, and divest most of the pharmaceutical assests in your stock portfolio to avoid C.O.I., please email me privately and I will give you the email address of one of the program heads at OSHI. There are at least 2 MM reps and probably 3. One however no longer joins our monthly training updates. Because of the (unfortunately) paucity of new myeloma agents coming to the FDA, OSHI might say they have enough MM PRs....but please ask if you are genuinely interested. I think it is a worthwhile undertaking.

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