Non-hormonal drug gabapentin (Serada) to treat menopausal hot flashes shows promise: Depomed

Non-hormonal alternative drug Serada has been found effective in menopausal hot flashes in state-stage clinical studies, according to the developer of the drug Depomed.

Depomed’s Serada is an extended-release formulation of gabapentin.

Depomed has developed Serada using its proprietary Acuform drug delivery technology for the treatment of menopausal hot flashes.

By combining gabapentin with Acuform technology, Serada is absorbed slowly into the upper gastrointestinal tract over several hours rather than immediately.

Immediate release formulations of gabapentin have been approved by the FDA to treat neuropathic pain and epilepsy.

Depomed has conducted BREEZE 1 and 2 Phase 3 clinical trials evaluating the safety and efficacy of Serada in two doses.

In each BREEZE study, patients were randomized into three treatment arms: placebo; Serada 1200mg dosed once daily; or Serada 1800mg twice daily (dosed 600mg in the morning and 1200mg in the evening). BREEZE 1 and 2 combined enrolled 1,100 patients.

The four co-primary efficacy endpoints in both studies were the reductions in the mean frequency of moderate to severe hot flashes, and the average severity of hot flashes, measured after four weeks and 12 weeks of stable treatment.

Patients in the BREEZE 2 study received twelve weeks of treatment, while patients in the BREEZE 1 study were treated for six months in order to assess safety and persistence of efficacy.

In the higher dose treatment arm of the two doses evaluated, gabapentin 1800mg dose achieved positive results at 4 weeks. All four co-primary endpoints of the 1800mg dose at 4 weeks demonstrated significant reductions in frequency and severity in both clinical trials.

In the lower dose treatment arm, gabapentin 1200mg dose at 4 weeks achieved statistical significance in three of the four co-primary endpoints. Frequency was significantly reduced in both clinical trials at four weeks.

Severity was significantly reduced in only one trial Of the other four co-primary endpoints of the 1200mg dose at 12 weeks.

“There is a large unmet need for a non-hormonal hot flash therapy, and we believe Serada has the potential to address that need,” said Carl Pelzel, Depomed’s president and chief executive officer.

Serada was generally well tolerated in both BREEZE trials. The most common adverse events were dizziness and somnolence.

Depomed, Inc. is a specialty pharmaceutical company with one product candidate through Phase 3 clinical development, another in Phase 3 clinical development, two approved products on the market and other product candidates in its early stage pipeline.

Depomed’s candidate DM-1796 has completed Phase 3 clinical development and has been licensed to Solvay Pharmaceuticals. A New Drug Applications for DM-1796 is expected to be filed with the FDA in the first quarter of 2010. Product candidate Serada is in Phase 3 clinical development for menopausal hot flashes.

Glumetza (metformin hydrochloride extended release tablets) is approved for use in adults with type 2 diabetes and promoted by Santarus, Inc. in the United States.

What are post-menopauasal hot flashes?

Hot flashes are characterized by a sudden, temporary onset of body warmth, flushing and sweating. Hot flashes are disruptive and impact women’s overall quality of life, affecting their mood and their ability to sleep. In fact, insomnia typically worsens with the severity of hot flashes. According to the North American Menopause Society, hot flashes are the most common menopause-related discomfort. Research suggests hot flashes occur when the body’s internal thermoregulatory mechanism (located in the hypothalamus) becomes irregular, narrowing the body’s thermoneutral zone. Thus, even small fluctuations in body temperature can cause menopausal women to experience perfuse sweating or severe chills that would not affect a person with a properly functioning thermoregulatory mechanism. Hot flashes affect 32 million women in the U.S. annually.