BETHESDA, MD. – Advisers to the Food and Drug Administration voted 20-2 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 long-term data and the potential for illicit use of the drug.
At a joint meeting, panelists generally agreed 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. They said the effect was modest, and that treatment may benefit only a subset of patients. They also said 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 with other treatments for the disorder–milnacipran (Savella), pregabalin (Lyrica), and duloxetine (Cymbalta).
Sodium oxybate is the sodium salt of gamma hydroxybutyrate, an endogenous neurotransmitter synthesized from gamma aminobutyric acid, and is also known as the “date rape” drug. It was approved in an oral solution in 2002 for narcolepsy and has been marketed as Xyrem by Jazz Pharmaceuticals, with a risk evaluation and mitigation (REMS) program that tightly controls distribution of the drug.
The panelists' and FDA reviewers' main concern was that if the drug were approved for fibromyalgia, its use would increase substantially and its availability as a street drug could also increase, despite the controlled distribution.
They 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, 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 III randomized, double-blind, controlled 14-week studies, two different doses of sodium oxybate were compared with placebo in about 1,000 fibromyalgia patients aged 18 and older, who discontinued opiates, benzodiazepines, muscle relaxants, and other medications or devices. A significantly greater proportion of those on sodium oxybate (36%-46%) met the primary end point, at least a 30% reduction in pain from baseline to the end of treatment, compared with placebo (20%-27%). Adverse events were similar to those observed in Xyrem trials.
The FDA usually follows its advisory panels' recommendations. Panelists have been cleared of potential conflicts related to the meeting topic, although in some cases, a waiver is granted to a panelist.