A joint US Food and Drug Administration (FDA) advisory committee has come out strongly against approval of the central nervous system depressant sodium oxybate (Xyrem; Jazz Pharmaceuticals, Inc) for the treatment of fibromyalgia.
Members of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted 20 to 2 against expanding the drug’s current indication for narcolepsy, citing concerns about sodium oxybate’s safety and voicing fears about the potential for abuse and misuse.
The committee discussed a number of issues before holding the final vote, including whether sodium oxybate was effective, whether it improved sleep for fibromyalgia patients, and whether the Risk Evaluation and Mitigation Strategy (REMS) proposed by Jazz was enough to address the potential for abuse and misuse that would inevitably arise as a result of the drug’s expanded use. Also known as gamma-hydroxybutyrate, or GHB, sodium oxybate has been called the date rape drug.
Many committee members said that although they believed that the drug was effective treatment for some fibromyalgia patients, they felt the data could be strengthened if the sponsor did larger studies of longer duration, compared sodium oxybate with currently available fibromyalgia medications, and improved the REMS program. However, the main focus of the panel was safety.
“There is no clear evidence that this is better than any of the drugs on the market to treat fibromyalgia. And because there is such a knock-out potential, it would be very difficult for me to believe that there was really adequate control. So you’ve got something that is much riskier than any of these other 3 drugs, and arguably no more effective,” said Sidney Wolfe, MD, director of Public Citizen’s Health Research Group, in Washington, DC.
“I think this drug is extraordinarily dangerous. It would have to be shown to be significantly better than other drugs in a superiority study and limited to people who did not respond to any of the safer pharmacologic treatments. To unleash this drug on such a large population without knowing that it is significantly superior to the other drugs would be a huge mistake,” Dr. Wolfe added.
Kathleen O’Neil, MD, from the University of Oklahoma College of Medicine, who chaired the meeting, said she believed in the drug’s efficacy, but was less sure about its safety.
“My feeling is that this drug should go forward, but not right now, because I think we have too many safety questions to answer. The real issue is how safe [it is] — particularly in special populations. I also think the REMS needs to be strengthened,” she said.
John Markman, MD, from the University of Rochester Medical Center, New York, agreed with Dr. O’Neil that sodium oxybate has promise. “I voted no, but I think there is significant potential for this drug as a therapeutic option for patients with fibromyalgia, and I would encourage the sponsor to continue to pursue this because I do think there is compelling evidence here of pain-relieving benefit or analgesic signal from the studies we’ve seen today. But it’s important that we balance the risk, given the other treatment options.”
Barbara Berney, from Rockford, Illinois — the patient representative on the panel — said she understood the panel’s safety concerns but asked committee members to consider the plight of patients with fibromyalgia who do not respond to currently available drugs.
“For those of us with fibromyalgia, anything you can add to the arsenal would be a huge benefit. There will be safety issues, but I also think that because there is so little else available, you really need to think about those people who have suffered for as many years as they have, with nothing, and how much of a difference sodium oxybate could make to them,” said Ms. Berney.
However, when it came to the vote, Ms. Berney voted no. “This was an extremely difficult vote for me, because while I do feel that it is efficacious, and it will help many patients who are nonresponders, I voted no on the basis of safety concerns.”
Sodium oxybate is given in 2 doses. After the first dose, the patient falls asleep immediately and then must wake up again 2 hours later to take the second dose, setting an alarm to do so in many cases. This bothered Ms. Berney.
“As a patient myself I cannot imagine taking one dose, and having to wake up 2 to 4 hours later to take another dose — simply because it’s hard enough to get to sleep and it’s hard enough once I am asleep to go back to sleep once I have awakened.”
Richard Meisch, MD, PhD, from the University of Texas Health Science Center at Houston Medical School, Texas, was one panel member who voted in favor of the expanded use. “This is not a new drug. It’s already out there, and the benefits seem to exceed the risks for this serious disorder.”
Joining Dr. Meisch in a yes vote was Dennis Dixon, PhD, from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
“I believe that the efficacy studies were adequate and well controlled. The results are impressive. I think the evidence on safety to the individuals who participated in the studies is completely acceptable. There were minimal side effects,” said Dr. Meisch.
He added that he was sympathetic to the suggestions for additional studies and additional questions that could be addressed, but doubted that they could be carried out. “Those are truisms. It’s always the case that there are more questions that could be addressed, and I don’t think that any of those represent the sort of gap in knowledge that should lead to a delay in making the drug available.”