The Food and Drug Administration has decided that the sedative-hypnotic drug sodium oxybate cannot be approved for treatment of fibromyalgia, based on the information currently included in the approval application, the manufacturer announced on Oct. 11.
The statement issued by Jazz Pharmaceuticals noted that the FDA’s “complete response letter” said that the new drug application for sodium oxybate cannot be approved “in its present form” and cited the need for more clinical studies. The FDA’s letter also discusses the proposed Risk Evaluation and Mitigation Strategy (REMS), as well as the concentration and trade name for sodium oxybate, according to Jazz.
Other topics discussed in the letter include the need for methods to ensure safe use of the drug, the sodium salt of gamma hydroxybutyrate, an endogenous neurotransmitter synthesized from gamma aminobutyric acid, which is also known as the “date rape” drug for its potent sedative effects.
It is the FDA’s practice to send complete response letters to sponsors of new drug applications when there are concerns about whether the drug should be approved and to outline information needed to complete the approval process. The agency does not comment on products under review, and therefore does not release information on these letters; it is up to the companies to release this information.
The concerns that the Jazz statement said were outlined in the letter reflect those expressed by members of two FDA advisory panels at an August meeting held to review the data on sodium oxybate for the fibromyalgia indication. At the meeting, the majority of the panelists voted against recommending approval, citing the lack of long-term data and other concerns regarding the drug – including its potential for illicit use. The drug’s only approved indication is for the treatment of narcolepsy, a fairly uncommon condition. Were sodium oxybate to be approved for fibromyalgia, which is more common, it is possible that the drug would be more likely to be misused because it would be present in more family medicine cabinets.
Sodium oxybate is also the active ingredient in Xyrem, which is approved for treating excessive daytime sleepiness and cataplexy in adults with narcolepsy. The availability of Xyrem is tightly controlled through a REMS, which includes restricted distribution through one centralized pharmacy. The company had proposed that the drug be marketed under a different trade name for fibromyalgia, with a different REMS, which panelists said could be confusing and could increase medical 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. Panelists were also concerned that leaving the second dose by the bedside table could increase the chance it would be used illicitly or ingested accidentally by children.
In two phase III, 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 years and older. All the patients 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 end point, 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.
The Jazz statement says that the company has requested a meeting with the FDA to discuss the complete response letter, and will then evaluate the next steps for the drug, which the company believes could meet a “significant unmet medical need among fibromyalgia patients,” if approved, Bruce Cozadd, chairman and chief executive officer at Jazz said in the statement.
Xyrem is also approved in the European Union and Canada for treating symptoms associated with narcolepsy. The drugs currently approved for treating fibromyalgia in the United States are milnacipran (Savella), pregabalin (Lyrica), and duloxetine (Cymbalta).