Recognizing myeloma patients' need for options, the FDA's Oncologic Drugs Advisory Committee (ODAC) voted 11-0 Wednesday, with one abstention, that the benefits of Onyx Pharmaceuticals Inc.'s Kyprolis outweigh its risks as a third-line treatment for relapsed and refractory multiple myeloma.

Whether the FDA follows through with the committee's recommendation and grants Kyprolis (carfilzomib) accelerated approval by its July 27 PDUFA date could make a lot of difference for some patients who have run out of new therapies to try.

While Onyx based its accelerated approval application on the data from an open-label, single-arm Phase IIb trial that treated 768 subjects, it has completed enrollment in a large Phase III confirmatory trial of the second-generation proteasome inhibitor. In fact, carfilzomib currently is being evaluated in three Phase III trials and others are in the works.

But if it has to wait for results from the confirmatory trial, carfilzomib wouldn't be available for approval until 2014 or 2015, said Ted Love, executive vice president for R&D and technical operations at South San Francisco-based Onyx. That could deprive up to 35,000 patients access to a drug that could impact their survival.

A number of those patients spoke up during a public comment period at the ODAC meeting, saying they understand there are risks, but they are willing to take them if it means they have treatment options that could prolong their lives.

James Omel, a doctor and patient representative on the committee, agreed with the other patients who spoke up, calling myeloma a "sneaky disease," for which there is no cure. Patients are willing to face the risks of carfilzomib, he said, because "we know what the risk of myeloma is."

He also reminded the committee of the constant need for new myeloma drugs. Once myeloma is controlled, it finds new escapes and attacks again.

No new myeloma drugs have been approved in the U.S. in six years, said Robin Tuohy, the wife of a myeloma patient and director of support groups at the International Myeloma Foundation.

In its review of carfilzomib, the FDA has not echoed the sense of urgency expressed by patients. While it recognized the high unmet medical need in relapsed and refractory multiple myeloma, the agency granted the drug a standard 10-month review time, instead of priority review. (See BioWorld Today, Dec. 13, 2011.)

Prior to Wednesday's meeting, the FDA raised concerns over severe cardiac toxicities and the possibility that carfilzomib may not offer an advantage over existing multiple myeloma therapies. (See BioWorld Today, June 19, 2012.)

At the meeting, the agency again expressed concern about deaths associated with cardiac events and hepatic failure, but it acknowledged that the frequency of serious adverse events (SAEs) was low even though the trial population had previously undergone heavy treatment with other therapies.

Since trial eligibility required subjects to have failed both a proteasome inhibitor and an immunomodulatory agent, Onyx officials pointed out that patients in the Phase IIb trial generally had the disease at least a year longer than those in studies of the other therapies. Yet the frequency of SAEs was similar to that seen in trials for Velcade (bortezomib, Millennium/Takeda Pharmaceutical Co. Ltd.) and other approved myeloma drugs.

ODAC Chairman Wyndham Wilson agreed, saying the cardiac toxicity for carfilzomib did not seem to be out of proportion for "an unmet need in a group that has run out of options."

Wilson, chief of the lymphoma therapeutics section at the National Cancer Institute, did question how a company can do a confirmatory trial for an indication such as refractory myeloma when the drug is available to patients under accelerated approval. If patients could get the new drug, there's no reason for them to enroll in a trial where there's a chance they wouldn't get it, he said.

Earlier in the day, ODAC voted 14-1-1 against Sanofi SA's semuloparin as a prophylactic for venous thromboembolism in certain cancer patients on chemotherapy. Despite its thumbs down for the anticoagulant, the committee encouraged the drugmaker not to give up on the drug. A big part of the problem, ODAC said, was the trial itself.

Onyx shares (NASDAQ:ONXX) were up slightly Wednesday morning, reaching a high of $45. 10. But trading was halted in the afternoon as ODAC began its discussion of carfilzomib. In afterhours trading, shares were selling at $44.49.