Depomed, Inc. Says Gabapentin GR Study Misses Main Goal
The randomized, double-blind, placebo-controlled, multi-center trial involved 407 PHN patients. Patients were randomized into one of three treatment groups for ten weeks of treatment: Gabapentin GR once-daily, Gabapentin GR twice-daily (each with 1800 mg total daily-dose) and placebo. The primary endpoint of the study was to assess the efficacy of Gabapentin GR compared to placebo in reducing average daily pain scores from baseline to endpoint. Secondary objectives included generating data on safety, sleep interference and global impressions of changes in pain by investigators and patients.
Results
The primary endpoint was not achieved with statistical significance for either active treatment regimen, as compared to placebo, over the ten-week treatment period. The mean reductions in average daily pain scores from baseline to end of study were 1.83 (once-daily), 1.72 (twice-daily) and 1.43 (placebo). However, statistical significance relative to placebo was achieved in each of the first six weeks for the once-daily treatment arm and in each of the first five weeks for the twice-daily treatment arm. Pain scores in the placebo group continued to improve in the last four weeks of the study.
The secondary endpoints of sleep interference, Clinical Global Impression of Change or CGIC (a scale used by physicians for overall assessment of patient improvement) and Patient Global Impression of Change or PGIC (a scale used by patients to report their overall assessment of change) were all statistically significant for the once-daily treatment compared to placebo over the ten week study period. Sleep interference scores were reduced by 2.01 points with Gabapentin GR compared to -1.39 with placebo (p=0.014). Physicians reported that 48.0% of patients taking Gabapentin once-daily were "very much improved" or "much improved" compared to 27.1% of the patients who received placebo (p is less than0.001), as measured by the CGIC. Similar results were observed for the PGIC in the once-daily and placebo arms (p=0.009).
The most common side effect observed was dizziness, which is commonly associated with gabapentin. In the trial, the incidence of dizziness for Gabapentin GR was 10.1% (once-daily) and 14.9% (twice-daily) as compared to 3.0% for placebo. Somnolence was observed in 2.9% of once-daily treated patients and 6.7% of twice-daily treated patients, compared to 2.3% of patients on placebo. Peripheral edema occurred in 5.1% of the once-daily treated population and 4.5% in the twice-daily population compared to no incidents of peripheral edema in the placebo group.
"The Phase 3 results we received today were very surprising and disappointing to us in light of the encouraging safety and efficacy data that we observed in our phase 2 clinical trial, in which we achieved statistically significant results in a four-week period as compared to placebo." said John W. Fara, Ph.D., chairman, president and chief executive officer of Depomed. "We are particularly surprised to see a high placebo effect that persisted throughout the trial as compared to other large published PHN trials. We saw clinically meaningful and statistically significant reductions in pain scores from baseline to the ten-week endpoint in both active treatment arms. However, the unexpected improvements in the pain scores of the placebo group during the last four weeks of the study prevented the achievement of statistical significance in the primary endpoint that is required by the FDA."
"We will be evaluating these results internally and with potential partners to determine how best to proceed with Gabapentin GR in pain indications," said Carl Pelzel, Depomed's executive vice president and chief operating officer. "We do not expect these results to have an impact on our ongoing clinical development program in menopausal hot flashes."
About Gabapentin GR
Gabapentin GR is an investigational extended release and gastric retained formulation of gabapentin, an FDA-approved product for the treatment of PHN. Formulated with Depomed's proprietary AcuForm(TM) drug delivery technology, Gabapentin GR holds the potential to offer patients the pain-relief benefits provided by immediate release formulations of gabapentin, with fewer side effects and a more convenient once- or twice-daily dosing regimen. The formulation of once- or twice-daily Gabapentin is particularly challenging since Gabapentin is absorbed through an active transport mechanism which is concentrated in the upper gastrointestinal tract. Therefore a gastric retained formulation of Gabapentin, such as Gabapentin GR, may demonstrate an improvement in delivering drug to these active transport sites compared to a more traditional extended release technology. In 2006, 16.3 million prescriptions for gabapentin were dispensed.
About Postherpetic Neuralgia
Neuropathic pain affects approximately 2.6 million individuals in the United States. Postherpetic neuralgia (PHN) is a persistent neuropathic pain condition caused by nerve damage after a shingles, or herpes zoster, viral infection. It afflicts approximately one in five patients diagnosed with shingles, or approximately 150,000 individuals in the United States. The incidence of PHN increases in elderly patients, with 75 percent of those over 70 years old who have shingles, developing PHN. The pain associated with PHN reportedly can be so severe that patients are unable to resume normal activities for months. Since there is currently no cure for PHN, treatments are focused on relieving pain.
About Depomed
Depomed, Inc., is a specialty pharmaceutical company with two approved products on the market and multiple 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(TM) (metformin hydrochloride extended release tablets) is approved for use in adults with type 2 diabetes and is being marketed in the United States by King Pharmaceuticals and in Canada by Biovail Corporation. ProQuin® XR (ciprofloxacin hydrochloride) extended release tablets are approved in the United States for the once-daily treatment of uncomplicated urinary tract infections. Depomed's product candidate Gabapentin GR(TM) is currently in Phase 3 and Phase 2 clinical development for the treatment of two pain indications, postherpetic neuralgia and diabetic peripheral neuropathy, respectively. A Phase 2 clinical trial of Gabapentin GR in menopausal hot flashes is also under way. Additional information about Depomed may be found on its web site, www.depomedinc.com.
"Forward-looking Statement" Statements in this press release that are not historical facts are forward-looking statements that involve risks and uncertainties including, but not limited to, those related to our results and timing of our Gabapentin GR clinical studies; potential benefits of Gabapentin GR; our research and development efforts, including pre-clinical and clinical testing; regulation by the FDA and other government agencies. 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 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.
Contact: Depomed, Inc. Mohamad Tabrizi, 650-462-5900
Source: Depomed, Inc.