Orphan Medical Announces Positive Xyrem Clinical Results in Second Excessive Daytime Sleepiness Trial

Trial Supports Use of Xyrem as Monotherapy for Narcolepsy

Minneapolis, MN - September 15, 2004

Orphan Medical, Inc. announced positive results from a Phase III (b) trial designed to evaluate the improvement of excessive daytime sleepiness (EDS) associated with narcolepsy when Xyrem(R) (sodium oxybate) oral solution is used alone or with modafinil (Provigil(R)), a wakefulness promoting agent approved for the treatment of EDS.

The primary endpoint of the trial was EDS as measured by the objective Maintenance of Wakefulness Test (MWT). The secondary endpoint also measured EDS using the Epworth Sleepiness Score. The trial demonstrated that Xyrem monotherapy is effective in the treatment of EDS associated with narcolepsy as measured by objective response in the MWT.

The combined use of Xyrem and modafinil showed a greater response than either agent alone. EXCEEDS (Evaluation of Xyrem to Check Efficacy in Excessive Daytime Sleepiness) was a double-blind, placebo-controlled, parallel group multi-center randomized study.

This data follows the June announcement of positive clinical results from the Company's SXB-15 trial which evaluated the benefits of Xyrem in EDS associated with narcolepsy where the use of Xyrem was incremental to the use of stimulants or wakefulness-promoting drugs. In that trial, adding Xyrem resulted in statistically significant improvement in EDS as measured by The Epworth Sleepiness Score (ESS), the Clinical Global Impression of Change (CGIc) and the MWT.

Bill Houghton, M.D., Orphan Medical Chief Medical & Scientific Officer, said, "Together, these two trials now demonstrate that Xyrem can be proposed as first-line therapy in narcolepsy, since Xyrem data has been produced to show efficacy in treating the symptoms of EDS, cataplexy and fragmented nighttime sleep."

John H. Bullion, Orphan Medical Chief Executive Officer, stated, "The results of EXCEEDS further support our belief that Xyrem represents the foundation for the treatment of narcolepsy. We intend to file a Supplemental New Drug Application (sNDA) incorporating the results of both EDS trials with the U.S. Food and Drug Administration (FDA) by the end of the year. The sNDA timing will position the Company for an FDA decision in 2005 that could allow us to expand the use of Xyrem to all of narcolepsy."

Narcolepsy is a chronic, debilitating neurological disease characterized by symptoms of excessive daytime sleepiness, cataplexy (sudden loss of muscle tone) and fragmented nighttime sleep. Excessive daytime sleepiness is experienced by all narcolepsy patients and is usually treated with stimulants during the day to help keep patients awake. Xyrem is currently the only approved medication for the treatment of cataplexy.

Trial Results

The trial was conducted in narcoleptic patients with established EDS for which they were treated with modafinil at doses of 200-600 mg daily. After meeting entry criteria, and following two weeks of blinded randomized treatment with modafinil and Xyrem placebo, they were randomized to four evenly distributed groups in the trial with one group receiving active Xyrem only, another with active modafinil alone, a third group with both active medications, and a final group receiving both Xyrem and modafinil placebo.

As expected, the group receiving both active medications saw the greatest mean change of 2.7 minutes from baseline while maintained in blinded fashion on unchanged dose of modafinil. It is not yet known if the two products are additive or synergistic in their benefit. The Xyrem, modafinil and combined drug treatment groups were highly statistically significant compared to the placebo group. Changes in the Epworth Sleepiness Score (ESS) were also measured and those results further support the MWT data.

The safety profile seen in this study was consistent with other controlled clinical trials, with a relatively uniform distribution across all groups. The side effect of nausea occurred more often for groups receiving Xyrem and both Xyrem and modafinil together, as did vomiting which had a markedly lower rate of incidence.

Headache was a common symptom in all groups, including placebo, but dizziness and tremor were more common in the group on both drugs, as was anxiety. The incidence of sleep walking and enuresis, previously reported in our studies as associated with Xyrem showed a very low incidence in this study that was not significantly different between groups.

Background Information

Narcolepsy is a chronic, debilitating neurological disease. Cataplexy, a sudden loss of muscle tone, is usually triggered by strong emotions such as laughter, anger, or surprise. As such, patients often selectively isolate themselves from interaction with others resulting in a dramatic effect on a patient's quality of life. Narcolepsy afflicts approximately 100,000 to 140,000 Americans with about 50,000 to 75,000 patients receiving some form of treatment for their symptoms. An estimated sixty to ninety percent of those with narcolepsy suffer from cataplexy. All patients with narcolepsy suffer from excessive daytime sleepiness.

Orphan Medical acquires, develops, and markets pharmaceuticals of high medical value for inadequately treated and uncommon CNS diseases treated by specialist physicians. The lead product for the company is Xyrem, which is the first and only approved treatment for cataplexy associated with narcolepsy. Xyrem has now been assessed as a treatment for the full range of narcolepsy symptoms including excessive daytime sleepiness. Orphan Medical's pipeline includes development stage products for fibromyalgia and pain. Orphan Medical's Internet Web site address is www.orphan.com.

The information in this press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. In some cases, you can identify forward looking statements by terminology such as "expects," "anticipates," "intends," "may," "should," "plans," "believes," "seeks," "estimates," "could," "would" or the negative of such terms or other comparable terminology. Such forward-looking statements are based upon current expectations and beliefs and involve numerous risks and uncertainties, both known and unknown, that could cause actual events or results to differ materially from these forward-looking statements. A number of factors could cause actual results to differ materially from the Company's assumptions and expectations. These are set forth in the cautionary statements included in Orphan Medical's most recent Form 10-Q or Form 10-K filed with the Securities and Exchange Commission. (These documents can be accessed through the Orphan Medical Web site at http://www.orphan.com ). All forward-looking statements are qualified by, and should be considered in conjunction with, such cautionary statements.