What is Project GHB, Inc.'s Response?

The approval of Xyrem (GHB) does not change the purpose of Project GHB, Inc. It may make the effort of saving lives harder.

Our concerns are these: Although the FDA has approved this drug, they fundamentally have NO real knowledge about it. The FDA cannot tell you how it works or what the long-terms effects may be. The National Institute of Drug Abuse (NIDA) last year released a large amount money for research into the basics of GHB because of the significant lack of knowledge about how this drug works and what it really does. Approval DURING that research, instead of awaiting the results, seems premature. Testing capabilities for GHB--for both law enforcement and medical purposes--is still in its infancy at this time, making control and identification of it difficult. And, we are concerned that the approval of Xyrem will send a false sense of safety to abusers everywhere. This does not in any way mean that GHB is "safe" for any purposes other than the limited medical condition for which it was approved.

As has always been our position, Project GHB has a very real concern for sufferers with the combined condition of Narcolepsy and Cataplexy. It has never been our intention to thwart any efforts in finding these patients treatments that work. As it states on our website:

"Project GHB, Inc. has corresponded with many narcolepsy patients and we do realize the debilitating effects of this condition... Nor are we against research aimed at treating this terrible condition. Our organization is targeted toward educating people about the abuse of GHB."

It is important to clarify that GHB, in the form of Xyrem, is approved for the limited use in narcolepsy/cataplexy. It was not deemed to be effective for sleep disorders alone, but only in the reduction of cataplexy attacks, which are typically accompanied by the condition of narcolepsy. Abuse of the Xyrem product is illegal. GHB from any other source (and the GHB analogs) remains a Schedule I drug, illegal to possess, transport, manufacture and to provide to others. Selling or giving it to someone, whether they knowingly ingest it or whether it is slipped to them, could result in arrest and prosecution for murder or manslaughter. Abuse of GHB can result in overdose, addiction or even death.

And, so, we will continue educating the public about the dangers of GHB, including Xyrem. It WILL be abused, like many prescription medications. Hopefully we can play a part in minimizing the abuse.
 

*Editor's note: These results are as stated from the Orphan Medical Company. Xyrem (R) is the brand name Orphan Medical uses for sodium oxybate (GHB).

2 previous Company Press Releases

Monday December 4, 2:25 pm Eastern Time

Orphan Medical Announces Xyrem(R) (Sodium Oxybate) Oral Solution NDA Accepted for Filing by the FDA

MINNEAPOLIS, Dec. 4 /PRNewswire/ -- Orphan Medical, Inc. (Nasdaq: ORPH - news) announced that the Food and Drug Administration (FDA) has notified the Company that its New Drug Application (NDA) for Xyrem® (sodium oxybate) oral solution as a treatment for the symptoms of narcolepsy has been accepted for filing. Orphan Medical previously announced that the FDA granted priority review classification for the Xyrem NDA on October 17, 2000. This means that the FDA has a goal of reviewing the NDA within a six-month time frame from the October 2, 2000, date of submission. The FDA grants priority attention and resources to new drugs that represent a significant advancement over available therapy.

Narcolepsy is a chronic neurological disorder affecting an estimated 100,000 to 125,000 Americans, whose main symptoms are excessive daytime sleepiness and cataplexy. Narcolepsy is accompanied by fragmented sleep throughout a 24-hour period whereas persons without the disease usually have more consolidated and organized sleep at night. The symptom of excessive daytime sleepiness afflicts all narcolepsy patients. Cataplexy is a debilitating symptom characterized by loss of muscle control in response to strong emotional reactions such as laughter, anger, or surprise. In its most severe form, cataplexy can cause a person to collapse during waking hours.

The information in this press release may contain forward-looking statements within the meaning of the Private Securities Litigation reform Act of 1995. 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 Exhibit 99 to 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.

CONTACT: Orphan Medical, Inc.
John Howell Bullion (CEO) or
Tim McGrath (CFO)
952-513-6900

Wednesday January 19, 7:32 am Eastern Time

Orphan Medical Reports Positive Clinical Trial Results for Xyrem(R), Potential Treatment for Narcolepsy

MINNEAPOLIS, Jan. 19 /PRNewswire/ -- Orphan Medical, Inc., dedicated to the development of therapeutics for patients with inadequately treated or uncommon diseases, announced today results of two clinical trials showing measurable benefits from Xyrem® (sodium oxybate) oral solution, a drug proposed for the treatment of two primary symptoms of the sleeping disorder narcolepsy, a chronic neurological disorder. These are cataplexy, the sudden loss of muscle control precipitated by emotion, and EDS, excessive daytime sleepiness. According to clinicians, nothing commercially available treats both symptoms and current treatments are unsatisfactory and can produce serious side effects with long-term use. The placebo-controlled clinical results reflected an approximate 70 percent reduction in the median number of cataplexy attacks of patients receiving a nine-gram dose of Xyrem. Based on the same dosage, EDS was improved as measured by the Epworth Sleep Scale; a number of patients experienced reductions to the point of normal sleepiness. The studies were reported at First Union Securities' Brain and Spine Conference in New York.

Orphan Medical CEO John H. Bullion commented, ``We believe the clinical data presented today demonstrate that Xyrem is an important treatment for narcolepsy, particularly for its chief symptoms of cataplexy and EDS.

``We expect to submit a New Drug Application (NDA) to the Food and Drug Administration (FDA) later this year,'' he said. ``Since the FDA has already indicated that Xyrem qualifies for priority review status, we hope to obtain FDA approval to begin marketing Xyrem during the first half of 2001.''

According to Orphan Medical COO and Chief Medical Officer William Houghton, M.D., narcolepsy can seriously impair a patient's quality of life. The condition occurs in an estimated 125,000 U.S. patients, with cataplexy symptoms present in as many as 75,000 such patients. Dr. Houghton pointed out that cataplexy is currently treated with anti-depressants, either selective serotonin re-uptake inhibitors, such as Prozac®, or tricyclic anti-depressants.

``Long-term treatment with these REM (Rapid Eye Movement) suppressing compounds,'' he said, ``may be limited by the development of drug tolerance and such adverse side effects as dry mouth, weight gain, excessive heart palpitations, and loss of sense of self.'' Dr. Houghton added that Provigil® (modafinil), a drug approved early last year by the FDA for the treatment of EDS associated with narcolepsy, does not address cataplexy.

Clinical Data

The first Orphan Medical trial evaluated three dosage levels of Xyrem in a four-week, placebo-controlled, double-blind study. The primary endpoint of this 136-patient study, which was conducted at 18 sleep centers around the country, was the reduction in the total number of cataplexy attacks. Medications intended to control cataplexy were discontinued over three to four weeks upon each patient's entry into the trial. This action was followed by a ``washout'' period of 5 to 18 days during which the effects of any such medication were eliminated. Each patient's untreated symptoms were recorded in daily diaries over a baseline period of 14 to 21 days. After this baseline period, patients were randomly assigned a placebo or an active dose level of 3, 6, or 9 grams of Xyrem. All cataplexy events were recorded daily over four weeks.

After the first trial, all patients, including those previously taking the placebo, were given the opportunity to enter into a follow-on open label study. After another short washout period, the 118 patients in this second trial were provided active drug, titrated to levels deemed clinically effective by physician investigators.

During the first trial, the median number of weekly cataplexy attacks in patients who received the 9 gram dose of Xyrem decreased by a median of 68.6% in comparison to the baseline. When compared to the placebo response, the clinical improvement of patients on the 9 gram Xyrem dose was highly statistically significant (p= .0008). The same statistical analysis of the 6 gram dose of Xyrem yielded a corresponding p-value of 0. 0529, and the 3 gram dose yielded a p-value of 0.5235. The p-value measures the chance an event might have occurred randomly. A p-value of less than 0.05 usually indicates a high probability that a response occurs as the result of a particular treatment as opposed to having occurred by chance.

At the end of the four-week trial, it appeared that the treatment response in patients taking the 6 and 9 gram doses had not reached a plateau. This was confirmed in the follow-on trial that measured each patient's response to Xyrem across the following 30 weeks. Data from the second trial suggest that maximum benefit was reached in seven weeks for most patients and was then sustained.

Regarding the reduction of EDS -- the secondary endpoint of the clinical trials -- it was found that at the 9 gram dose of Xyrem, median excessive daytime sleepiness as measured by the Epworth Sleepiness Scale was reduced from a level of 18 to 12 during the initial four-week trial. Some patients at the 9 gram dose experienced reductions to levels below 10, the level under which sleepiness is considered normal. These positive changes are incremental to the effects of stimulants since patients were not removed from stimulants treating their excessive daytime sleepiness. During the follow-on trial, the median levels of excessive daytime sleepiness continued to decrease, reflecting the changes in cataplexy. The Company expects to initiate a Phase IIIb 18-month controlled trial in early 2000 to validate these results using additional measures of daytime sleepiness. The FDA has indicated that this study, which may permit additional, labeling claims, need not be included in the Xyrem NDA submission.

Xyrem was generally well tolerated at all dosage levels during both the four-week and follow-on trials. Most adverse events, or side effects, appeared to be dose related and often occurred early during the trials and abated over time. The most common adverse events were dizziness, nausea, headache, and enuresis (urinary incontinence during sleep).

The Company said the absence of rebound cataplexy following abrupt cessation of treatment with Xyrem was also a notable finding of the trials. When patients discontinued taking Xyrem, a patient's cataplexy returned slowly back to its baseline level. This compares to the sudden and potentially severe rebound cataplexy that occur when treatment with tricyclic anti-depressants and selective serotonin re-uptake inhibitors is discontinued.

In May 1999 the FDA recommended regulating illicitly manufactured gamma hydroxybutyrate (GHB) as a Schedule I Controlled Substance, while further recommending that medically-formulated, GHB-based products such as Xyrem should be regulated as Schedule III drugs. The U.S. House of Representatives voted 423 to 1 in September to list GHB as a controlled substance, generally in keeping with the FDA's recommendation. By unanimous consent, the U.S. Senate acted in November to require the Drug Enforcement Agency (DEA) to follow the FDA's recommendation. The House and Senate now must conform any differences between their respective bills before submitting final legislation to the White House for Presidential signature.

Bullion commented, ``We anticipate that this legislation can be signed before this Spring. The scheduling of illicitly manufactured and distributed GHB as a Controlled Substance will protect Xyrem for medically indicated patient use. We believe the overwhelming bipartisan passage of both the House and the Senate bills reflects thoughtful consideration of the serious medical needs of narcoleptic patients. Orphan Medical will do its part by preparing systems to carefully monitor the distribution of Xyrem. To date, we have no evidence that Xyrem has been used for anything but medical use in approved clinical protocols. We will work with the DEA to help ensure the responsible handling of this promising narcolepsy treatment.''

Orphan Medical is dedicated to patients with inadequately treated or uncommon diseases. To that end, the Company acquires, develops, and markets products of high medical value for patients within selected strategic therapeutic market segments. Orphan Medical's Internet Web Site address is http://www.orphan.com .

The information in this press release may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. 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 Exhibit 99 to Orphan Medical's most recent Form 10-Q or Form 10-K filed with the Securities and Exchange Commission. All forward-looking statements are qualified by, and should be considered in conjunction with, such cautionary statements.

SOURCE: Orphan Medical, Inc.