BETHESDA, Md. — Advisors to the Food and Drug Administration voted 20 to 2 that the risk-benefit profile of sodium oxybate did not support approval of the sedative-hypnotic drug as a treatment for fibromyalgia, citing concerns that included the lack of longterm data and the potential for illicit use of the drug.
At a joint meeting of the FDA’s Arthritis Advisory Committee and the Drug Safety and Risk Management Committee August 20, panelists generally agreed that the data from clinical trials showed that sodium oxybate, which is approved for treating cataplexy and daytime sleepiness associated with narcolepsy, was effective in treating fibromyalgia. Panelists said the effect was modest, and that treatment may benefit only a subset of patients. They also said that it was unclear whether the results could be generalized to the typical fibromyalgia population and that more studies were needed, including those directly comparing sodium oxybate to other treatments for the disorder.
Sodium oxybate is the sodium salt of gamma hydroxybutyrate (GHB), an endogenous neurotransmitter synthesized from gamma aminobutyric acid, it is also known as the “date rape” drug. Sodium oxybate in an oral solution was approved in 2002 for narcolepsy and has been marketed as Xyrem by Jazz Pharmaceuticals, with a risk evaluation and mitigation (REMS) program that tightly controls availability of the drug and includes restricted distribution of the agent through one centralized pharmacy and other measures.
A main concern voiced by panelists and FDA reviewers was if the drug were approved to treat fibromyalgia, its use would increase substantially—and its availability as a street drug could increase markedly, despite the controlled distribution.
The panelists were strongly against the company’s proposal to use a different commercial name (Rekinla), concentration, and dose. They also opposed a different REMS for the fibromyalgia indication, with distribution through 15 specialized pharmacies, which they said was confusing and would increase the likelihood of medication errors.
The company proposed that patients would take two doses, one before going to sleep and the second in the middle of the night, which was also cited as a disadvantage for patients.
In two phase 3 randomized, double-blind, controlled 14-week studies, two different doses of sodium oxybate were compared to placebo in about 1,000 fibromyalgia patients aged 18 and older, who discontinued opiates, benzodiazepines, muscle relaxants, and other medications or devices before enrollment. A significantly greater proportion of those treated with sodium oxybate (36%-46%) met the primary endpoint, at least a 30% reduction in pain from baseline to the end of treatment, compared with those on placebo (20%-27%). Adverse events were similar to those observed in Xyrem trials.
Xyrem is also approved in the European Union and Canada for the treatment of symptoms associated with narcolepsy. The company anticipates that the drug would be used to treat up to 120,000 people with fibromyalgia in the United States. The other drugs approved by the FDA for treating fibromyalgia are milnacipran (Savella), pregabalin (Lyrica), and duloxetine (Cymbalta).
The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts related to the topic of the meeting, although in some cases, a waiver is granted to a panelist.