By Kim Coghill
Orphan Medical Inc.'s stock dropped 29.5 percent Friday after the company said an FDA advisory committee had canceled its review of the new drug application for Xyrem, an oral solution used to treat narcolepsy and its symptoms.
The FDA's Peripheral and Central Nervous System Advisory Committee was scheduled to review and discuss the efficacy, safety and risk management of the drug on March 15. However, John Bullion, CEO of Minneapolis-based Orphan Medical, said the meeting was canceled because of questions surrounding some data. In October the company submitted the NDA and was granted priority review status for the treatment of narcolepsy, particularly cataplexy, and to improve the symptoms of excessive daytime sleepiness.
"This is what happens in the process," Bullion said. "We have been in contact with the FDA throughout this process, but clearly there were some questions about some of the data. The first order of business now is to determine from the data what needs to be done."
Regarding the dipping stock prices, Bullion said, "Obviously the market expected us to meet with the advisory committee and they are disappointed - we are not happy either. We will work to get more information to the Street."
Orphan Medical's stock (NASDAQ:ORPH) closed Friday at $9.375, down $3.937.
A statement released by the company in February indicated that the anticipated U.S. market for cataplexy is in the range of $50 million to $110 million annually. The total narcolepsy market is estimated in the $100 million to $200 million range annually in the U.S.
Xyrem (sodium oxybate oral solution) is a treatment for cataplexy, the sudden loss of muscle control, which is a serious symptom of narcolepsy. The drug is designed to work by consolidating the fragmented sleep patterns characteristic to narcolepsy into a more normal sleep pattern. Narcolepsy is a chronic neurological disorder affecting between 100,000 and 125,000 Americans, whose main symptoms are excessive daytime sleepiness and cataplexy.
The drug proved effective in two pivotal Phase II clinical studies. The results of a 136-patient placebo-controlled, double-blind study showed that patients receiving the high dose of Xyrem (9 grams) experienced 68.6 percent fewer attacks of cataplexy than their placebo counterparts. After completion of that study, 118 patients agreed to continue on Xyrem. The study investigators established the effective dose for each individual patient and monitored excessive daytime sleepiness. The 9-gram dose of the drug markedly reduced daytime sleepiness - some patients even obtained levels of sleepiness considered "normal." (See BioWorld Today, Jan. 20, 2000.)
Orphan Medical continues to conduct a Phase IIIb controlled clinical trial designed to assess the efficacy of Xyrem in treating excessive daytime sleepiness related to narcolepsy. Patient enrollment is under way and the clinical portion of the trial is targeted to be complete by the end of 2001.
Xyrem is a medical formulation of gamma hydroxybutyrate (GHB), an easily produced and often abused compound. When used with alcohol, home-brewed formulations of GHB can disable a person and has gained notoriety as a "date-rape" drug.
Former President Bill Clinton signed into law last February a bill that calls for the Schedule 1 regulation of the compound. This designation is the method by which illegal drugs are controlled. In order to allow the drug to be developed and prescribed, the law provides for all GHB products being studied under an FDA-approved protocol to be treated as a Schedule III substance, and provides for a Schedule III designation for any approved GHB products. (See BioWorld Today, Feb. 24, 2000.)
Aside from Xyrem, Orphan Medical's other products include busulfan IV formulation (Busulfex), which has received orphan drug designation from the European Agency for the Evaluation of Medicinal Products (EMEA) for use as conditioning treatment prior to hematopoietic progenitor cell transplantation. If the drug receives approval, the orphan drug designation results in 10 years marketing exclusivity in Europe. Pierre Fabre Medicament, Orphan's partner, would market the product in Europe.
Antizol (fomepizole) Injection, another Orphan Medical product, has received priority review status from the Therapeutics Products Programme in Canada for the upcoming efficacy supplemental for the additional indication of methanol poisoning. Paladin Labs Inc. markets and distributes Antizol in the Canadian market. Antizol is the first drug approved as an antidote for confirmed or suspected ethylene glycol poisoning by the FDA. n