Depomed Reports Positive Efficacy Data From a Phase 2 Trial of Gabapentin GR in the Treatment of Menopausal Hot Flashes
"We are very pleased with the performance of our product. It delivered clinically meaningful and statistically significant efficacy in the management of menopausal hot flashes and exhibited a good tolerability profile. The results should prove invaluable as we begin planning the design of our Phase 3 program, and will provide important insight to potential partners evaluating this opportunity," said Carl A. Pelzel, president and chief executive officer of Depomed. "We are excited to move this important program forward as it addresses an area of high unmet medical need, especially as concerns over the use of estrogen become more acute and as doubts deepen regarding the value of herbal remedies that are being used. The next step in our program will be to discuss the results of this study with the FDA during an end of Phase 2 meeting later this year."
The study included 124 menopausal women (approximately 30 per group) with recurrent, moderate to severe hot flashes and was conducted at eight sites in the United States. The total study treatment duration after screening and baseline was 13 weeks. The primary objective of the study was to investigate the relationship between blood plasma concentrations of gabapentin observed in menopausal women after administration of Gabapentin GR and the frequency of hot flashes in those women. The plasma concentration data (pharmacokinetics) and the hot flash frequency and severity data (pharmacodynamics) will be used to contsruct a PK/PD dose response model designed to identify the dosing regimen to utilize in a Phase 3 program. The dose response model is expected to be presented to the FDA at an end of Phase 2 meeting later this year.
In order to facilitate the generation of an optimal dose response model, patients in each of the three active treatment arms remained on a stable Gabapentin GR dose for five weeks at an initial dose (600mg once daily; 1200mg in divided 600mg doses; or 1200mg once daily), followed by five weeks on a stable, incrementally higher dose (1800mg in divided 600mg and 1200mg doses; 2400mg in divided 600 and 1800mg doses; and 3000mg in divided 1200mg and 1800mg doses). Each stable dosing regimen was preceded by a one-week titration period.
Commenting on the study design, Dr. Carl Peck, former head of FDA's CDER (Center for Drug Evaluation and Research) and Chairman of NDA Partners LLC, said "The FDA should really like this learning/confirming trial, which fits well with FDA's Critical Path Initiative on model-based drug development. This is a 'best in class', randomized, blinded, exposure-response evaluation of gabapentin's ability to decrease hot flashes that will both inform the pivotal Phase 3 trial design and may serve as independent evidence of effectiveness and safety." Dr. Peck consults for Depomed.
Gabapentin GR demonstrated a reduction in the frequency of moderate to severe hot flashes, and in the severity of hot flashes, in all active treatment groups, with statistical significance relative to placebo from baseline to the end of the study observed in the 1800mg and 2400mg treatment groups. In the 1800mg treatment group, the mean number of moderate to severe hot flashes was reduced from 10.1 at baseline to 2.7 at endpoint (p=0.016), with similar results in the 2400mg treatment groups, compared to an endpoint value of 5.1 for the placebo group.
Gabapentin GR was well tolerated in the study, with one, two, one and three patients, respectively, withdrawing due to adverse events from the placebo, 1800mg, 2400mg and 3000mg groups. The most common side effects observed in the study were headache, somnolence and dizziness.
The results of this study will be presented today, Tuesday, Feb. 12, 2008 at 11 AM ET by Carl A. Pelzel, president and CEO of Depomed, during the 10th Annual BIO CEO & Investor Conference to be held in New York, NY. Interested parties can access a live, or archived, webcast of the presentation on the company's website at www.depomed.com.
About Gabapentin GR
Gabapentin GR is an investigational, extended release formulation of gabapentin, an FDA-approved drug for the treatment of seizures and postherpetic neuralgia. Published data on the use of gabapentin in menopausal women provide investigational support for the efficacy of the compound to address hot flash symptoms. A study published in the July 2006 issue of Obstetrics & Gynecology reported that gabapentin appeared to be as effective as estrogen in treating hot flashes. Recent studies have suggested a link between hormone replacement therapy and breast cancer. In the Position Statement of the North American Menopause Society (NAMS) regarding treatment of menopause-associated vasomotor symptoms (2004), gabapentin is reviewed as a recommended nonhormonal option.
Formulated with Depomed's proprietary AcuForm drug delivery technology, Gabapentin GR holds the potential to offer women experiencing menopausal hot flashes the relief provided by hormone replacement therapy without the exposure to hormones, and with fewer side effects and a more convenient dosing regimen. The company has sublicensed the exclusive right to develop and commercialize gabapentin for the treatment of menopausal hot flashes under a U.S. patent held by the University of Rochester covering the use of gabapentin for the treatment of menopausal hot flashes.
About Hot Flashes
Approximately 80 percent of women in the United States have hot flashes at some level of intensity during perimenopause. Hot flashes, also known as vasomotor symptoms, are sudden waves of heat that can start in the waist or chest and work their way to the neck and face and sometimes over the rest of the body. Hot flashes are characterized by a sudden temporary onset of body warmth, flushing and sweating. Depending on the intensity of the hot flash, some women may experience headaches, fatigue, dizziness, or heart palpitations. The only government-approved single agent therapy in both the United States and Canada for treating this menopause-related symptom is prescription estrogen, which has been associated with increased risk of breast cancer, coronary heart disease, thromboembolism, stroke and dementia.
Depomed, Inc. is a specialty pharmaceutical company with two approved products on the market and other product candidates in its pipeline. The company utilizes its proven, proprietary AcuForm(TM) drug delivery technology to improve existing oral medications, allowing for extended, controlled release of medications to the upper gastrointestinal tract. Benefits of AcuForm-enhanced pharmaceuticals include the convenience of once-daily administration, improved treatment tolerability and enhanced compliance and efficacy. Glumetza(R) (metformin hydrochloride extended release tablets) is approved for use in adults with type 2 diabetes. Proquin(R) XR (ciprofloxacin hydrochloride) extended release tablets are approved in the United States for the once-daily treatment of uncomplicated urinary tract infections and will be marketed in the United States within the urology specialty by Watson Pharmaceuticals. Product candidate Gabapentin GR(TM) is currently in clinical development for the treatment of neuropathic pain and for menopausal hot flashes. Additional information about Depomed may be found on its web site, www.depomed.com.
"Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995. Statements in this press release that are not historical facts are forward-looking statements that involve risks and uncertainties. The inclusion of forward-looking statements, including those related to our clinical development programs, and potential benefits of our products and product candidates, should not be regarded as a representation that any of our plans will be achieved. Actual results may differ materially from those set forth in this release due to the risks and uncertainties inherent in our business, including, without limitation, risks and uncertainties related to: our research and development efforts, including pre-clinical and clinical testing; regulation by the FDA and other government agencies; the timing of regulatory applications and product launches; our ability to successfully commercialize our products; the success of our collaborative arrangements with development and commercialization partners; and other risks detailed in our filings with the Securities and Exchange Commission filings, including our most recent Annual Report on Form 10-K and our most recent Quarterly Report on Form 10-Q. You are cautioned not to place undue reliance on these forward-looking statements which speak only as of the date hereof. We undertake no obligation to revise or update this release to reflect events or circumstances that occur after the date of this release.
Ina Cu, 650-462-5900
Posted: February 2008