History of XYREM^®

What Is an Orphan Drug?

Orphan drugs are given special status by the government due to the rarity of the conditions they treat. Because these diseases are so rare, the market for them is small, making orphan drugs economically undesirable to produce. Government assistance, via tax breaks, subsidy for research, and exclusivity gives companies the incentive to produce these drugs.[1]

In 1983, the United States legislature enacted the Orphan Drug Act, with the aim of encouraging drug companies to provide a home for promising treatments for such disorders. The government offers incentives to encourage manufacturers to develop and market drugs that might not have been developed otherwise.[1][2]

These drugs go through the normal FDA approval process. Once an orphan drug is approved for marketing, a doctor may prescribe it to his or her patients. If the drug is still in the experimental stage, the manufacturer may make it available to individuals on a compassionate-use basis, or individuals may be able to enroll in a clinical trial.[1][3]

Timeline to FDA Approval

The FDA and Orphan Drug Act were instrumental in the development of XYREM:

1983: President Ronald Reagan signs the Orphan Drug Act into law.
1985: Gamma-hydroxybutyrate (GHB) is designated as an Orphan Drug.
1994: Sponsor is approached by the FDA Office of Orphan Products to begin investigation into GHB as treatment for narcolepsy.
1996: Sponsor submits an Investigational New Drug application (IND) and begins formal development of GHB as drug therapy.
1998: Sponsor opens a treatment IND for the study of GHB in treating patients with narcolepsy and cataplexy.
2000: Sponsor submits New Drug Application (NDA) requesting approval of XYREM [(sodium oxybate) oral solution (CIII)] to reduce the incidence of cataplexy and improve the symptoms of daytime sleepiness in patients with narcolepsy. FDA grants application priority review status.
2001: FDA schedules meeting of the Peripheral and Central Nervous System Drugs Advisory Committee in March to consider the safety and efficacy of XYREM. In July the FDA finds XYREM approvable for the treatment of patients with cataplexy who are being treated with concomitant CNS stimulants.
July 17, 2002: XYREM receives approval for treatment of cataplexy in patients with narcolepsy.*
June 27, 2005: Jazz Pharmaceuticals acquires XYREM.
November 4, 2005: XYREM receives its second indication for treatment of EDS in patients with narcolepsy.*
Source: [2]

*In XYREM clinical trials, approximately 80% of patients maintained concomitant stimulant use.

References:

^ US Food and Drug Administration. The Orphan Drug Act (as amended). Available at: http://www.fda.gov/orphan/oda.htm. Accessed March 18, 2008.
^ Neuman Ariel. GHB's path to legitimacy: an administrative and legislative history of Xyrem [LEDA at Harvard Law School]. April 2004. Available at: http://leda.law.harvard.edu/leda/data/629/Neuman.html. Accessed March 18, 2008.
^ US Food and Drug Administration. The Orphan Drug Act (as amended). Available at: http://www.fda.gov/orphan/oda.htm. Accessed March 18, 2008.

Important Safety Information

1. XYREM^® is a controlled substance. Controlled substances are medicines that, if abused, may lead to varying degrees of physical or psychological dependence. XYREM is a Schedule III drug — which means that it has a moderate dependence liability. If you sell, distribute, or give your XYREM to anyone else or use it for purposes other than what it was prescribed for, you may be punished under federal and state law by jail and fines.

2. It is very important to keep XYREM out of reach of children and pets.

3. XYREM can cause serious side effects including trouble breathing while asleep, confusion, abnormal thinking, depression and loss of consciousness. Tell your doctor if you have any of these problems while taking XYREM.

BOXED WARNING:

!Warning

Central Nervous System Depressant with Abuse Potential. Should not be used with alcohol or other CNS depressants. Sodium oxybate is a form of GHB, a known drug of abuse. Abuse has been associated with some important central nervous system (CNS) adverse events (including death). Even at recommended doses, use has been associated with confusion, depression, and other neuropsychiatric events. Reports of respiratory depression occurred in clinical trials. Almost all of the patients who received sodium oxybate during clinical trials were receiving CNS stimulants.

Important CNS adverse events associated with abuse of GHB include seizure, respiratory depression and profound decreases in level of consciousness, with instances of coma and death. For events that occurred outside of clinical trials, in people taking GHB for recreational purposes, the circumstances surrounding the events are often unclear (e.g., dose of GHB taken, the nature and amount of alcohol or any concomitant drugs).

XYREM is available through the XYREM Success Program^®, using a centralized pharmacy 1-866-XYREM88^® (1-866-997-3688). The Success Program provides educational materials to the prescriber and the patient explaining the risks and proper use of sodium oxybate, and the required prescription form. Once it is documented that the patient has read and/or understood the materials, the drug will be shipped to the patient. The XYREM Success Program also recommends patient follow-up every 3 months. Physicians are expected to report all serious adverse events to the manufacturer.