Orphan Medical Submits Complete Response to the Xyrem® NDA Approvable Letter

Minneapolis, MN - October 9, 2001

Orphan Medical, Inc. announced that it has submitted to the U.S. Food and Drug Administration (FDA) an amendment to its Xyrem® (sodium oxybate) oral solution New Drug Application (NDA). The amendment represents the Company's complete response to the Agency's Approvable Letter received on July 2, 2001 and requests approval of Xyrem, as a treatment for cataplexy associated with narcolepsy, by the end of the year. The FDA has a statutory six-month deadline for completing its review.

The amendment includes revisions to product labeling and the risk management program, a safety update of ongoing clinical trials, and respiratory data collected during all night polysomnographic recordings of narcolepsy patients in a trial completed in early 2001. The data was analyzed to determine the effects of escalating doses of Xyrem (4.5 to 9g/night) on the frequency and severity of events of sleep-disordered breathing, and on oxygenation during sleep. No respiratory depressant effects were identified from therapeutic doses of Xyrem. (Please see data section below.) The respiratory data were included to address the FDA's concern that Xyrem might have a depressant effect on respiration. The Company also made a commitment to conduct an acute exposure trial in respiratory compromised patients once approval is obtained.

"This amendment is an important step toward approval," said John Bullion, Orphan Medical Chairman and CEO. "In about three months' time Orphan Medical collected, analyzed, and presented information that we believe fully addresses the issues raised in the FDA's Approvable Letter. I am very proud of the concerted effort of the Orphan Medical team. We have diligently addressed all of the FDA's issues since it granted Xyrem priority review about a year ago. We have asked the FDA to approve this medicine by the end of the year since there is no approved medication for the treatment of cataplexy and narcolepsy patients need this medication to help control their disease."

Orphan Medical continues to work proactively with the FDA and with our producer of Xyrem drug product to resolve manufacturing issues in order to meet anticipated launch demands in the first year following FDA approval.

Narcolepsy is a chronic neurological disorder affecting an estimated 100,000 to 125,000 Americans, whose main symptoms are excessive daytime sleepiness and cataplexy. Cataplexy is a debilitating symptom characterized by loss of muscle control in response to strong emotions such as laughter, anger, or surprise. In its most severe form, cataplexy can cause a person to collapse during waking hours.

Medical Data

These results showed no dose-related changes in mean saturated oxygen values in arterial blood (SaO2), as determined by continuous pulse oxymetry monitoring throughout the night, with mean values maintained between 94.7% and 95.5%. Since previous pharmacokinetic studies had indicated that peak plasma concentrations (Tmax) occurred 30-60 minutes after dosing, and that higher plasma levels occurred in relation to the second nightly dose compared to the first, special attention was paid to these times of expected peak plasma concentrations. No changes in arterial oxygen saturation corresponded to these times.

Minor, variable changes in the incidence and severity of events of sleep-disordered breathing occurred throughout the study. These were classified as obstructive and mixed sleep apneas, central apneas and hypopneas and their corresponding indexes (events per hour expressed as the Apnea Hypopnea Index and the Respiratory Disturbances Index.) However, dose-related changes were not seen in the therapeutic dose range of 4.5 to 9g/night in incidence of events, their severity as reflected in lowest oxygen saturation at any time during the night (absolute values), or the duration of time of oxygen desaturation to values less than 90% or 80%.

Orphan Medical acquires, develops, and markets pharmaceuticals of high medical value for inadequately treated and uncommon diseases. The Company serves three strategic therapeutic market segments that are characterized by well-defined patient populations and served by physician specialists: oncology support, antidotes and sleep disorders. Orphan Medical's Internet Web site address is www.orphan.com