Depomed's extended release gabapentin did not demonstrate statistically significant efficacy in relieving the pain of patients suffering from postherpetic neuralgia compared to placebo in a Phase III study, the company reported July 10.

The specialty pharma attributed the failure to unexpected improvement in pain scores among the placebo group in the 407-patient study. In the study, patients were assigned to one of two treatment groups or placebo. Patients in the treatment groups received a total of 1,800 mg of gabapentin GR (an investigational extended-release and gastric-retained formulation) either once or twice daily.

PHN is a condition caused by nerve damage after a shingles, or herpes zoster, infection.

While patients showed "clinically meaningful and statistically significant reduction in pain scores from baseline to the ten-week endpoint in both treatment arms ... 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 FDA," Depomed CEO John W. Fara said.

Depomed will evaluate the results internally and with potential partners to determine next steps, added Chief Operating Officer Carl Pelzel. "We do not expect these results to have an impact on our ongoing clinical development program in menopausal hot flashes."

For the primary endpoint of pain relief over the ten-week treatment period, the mean reductions in average daily pain scores from baseline were 1.83 (once-daily), 1.72 (twice-daily) and 1.43 (placebo). Depomed notes that 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 arm. Pain scores in the placebo group, meanwhile, continued to improve in the last four weeks.

Secondary endpoints included safety, pain that interfered with sleep and global impressions of changes in pain by investigators and patients.

On the sleep interference endpoint, reports from metrics used by patients and physicians both were statistically significant for the once-daily treatment compared to placebo over the ten-week period. Physicians also reported that 48 percent of patients in the once-daily arm were "very much improved" or "much improved" compared to 27.1 percent of patients receiving placebo (p<0.001).

The most common side effect was dizziness, which is commonly associated with gabapentin, Depomed said. Somnolence and peripheral edema also were reported.

Immediate-release gabapentin (Pfizer's Neurontin and generics) is indicated for treatment of partial seizures in adults and children over 3 years, an indication Depomed was not seeking, and for postherpetic neuralgia. It is dosed three times a day for a total of 900 mg - 1,800 mg daily (¹ Also see "Depomed Starts Gabapentin Extended Release Pivotal Trial" - Pink Sheet, 10 May, 2006.).

Pfizer's Neurontin follow-on Lyrica (pregabalin) was approved for PHN and diabetic peripheral neuropathy at the end of 2004 and recently was approved for management of fibromyalgia (² Also see "Pfizer’s Lyrica Is First Drug Approved For Fibromyalgia" - Pink Sheet, 21 June, 2007.).

Depomed announced June 13 that dosing had begun in a Phase II trial of gabapentin GR for the treatment of menopausal hot flashes. The dose response study aims to enroll 108 women for 13 weeks of treatment. The primary endpoint is frequency and severity of hot flashes relative to baseline. Secondary endpoints include efficacy relative to placebo based on changes from baseline in average daily frequency and severity score of hot flashes, and sleep quality.

The company licensed the patent for use of gabapentin for the treatment of menopausal hot flashes from PharmaNova in 2006 after a study was published showing that gabapentin might be as effective as estrogen in treating hot flashes, offering a non-hormone therapeutic alternative.

Wyeth is also promoting its investigational serotonin-norepinephrine reuptake inhibitor Pristiq (desvenlafaxine) as a potential first non-hormone hot flash therapy. Pristiq is pending at FDA in that indication with action expected during July (³ Also see "Wyeth’s Pristiq Shows Reduction In Hot Flashes In Menopausal Women" - Pink Sheet, 9 May, 2007.).

The drug was deemed "approvable" in January as a treatment for major depressive disorder, and Wyeth said it anticipates submitting a complete response letter in August (⁴ Also see "Wyeth Suggests Pristiq Could Surpass Effexor XR In Depression Market" - Pink Sheet, 13 June, 2007.).

- Shirley Haley (s.haley@elsevier.com)

Depomed’s Gabapentin GR Fails Phase III Postherpetic Neuralgia Study

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