Serada™ (Gabapentin GR - Hot Flashes)

Serada™ is an investigational formulation of gabapentin, an FDA-approved immediate release pharmaceutical for the treatment of partial epilepsy and management of postherpetic neuralgia (PHN). Recently published studies suggest the potential application of gabapentin for the treatment of menopausal hot flashes. Based on these findings, the company has secured exclusive rights to develop and commercialize Serada™, an AcuForm™-enhanced formulation, for the treatment of menopausal hot flashes.

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. They 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. Each year approximately 32 million women in the United States experience menopausal hot flashes, of whom approximately 13 million seek treatment.

New Treatment Option Needed

Hormone replacement therapy (HRT) is currently the only FDA-approved single-agent therapy for the treatment of menopausal hot flashes. In 2003, prescriptions for HRT dropped dramatically following the National Institutes of Health’s decision to halt a large-scale clinical study of HRT due to preliminary results suggesting a correlation between HRT and an increase risk of breast cancer and cardiovascular disease.

Serada™ – A Potential New Treatment Option

In the July 2006 issue of The Journal of Obstetrics and Gynecology, results were published from a small-scale clinical study that compared the efficacy of estrogen and immediate release gabapentin in the treatment of moderate to severe hot flashes. Data from the study, which was led by Sireesha Reddy, M.D., at the University of Rochester, suggest that gabapentin may be as effective as estrogen in reducing the frequency and severity of hot flashes.

Serada™ could hold the potential to provide women suffering from menopausal hot flashes with a new treatment option that has more favorable safety profile than seen with HRT. Additionally, formulated with AcuForm™ drug delivery technology, Serada™ could hold the potential to be efficacious and have fewer of the side effects commonly seen with immediate release formulations of gabapentin, including dizziness and daytime sleepiness.

Clinical Results

On October 12, 2009, we announced top-line results from the BREEZE 1 and 2 Phase 3 clinical trials evaluating the safety and efficacy of Serada™, an investigational non-hormonal extended release formulation of gabapentin for the treatment of menopausal hot flashes.

In the higher dose treatment arm of the two doses evaluated, the 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 (p-values ranged from 0.0001 to 0.004). Of the other four co-primary endpoints of the 1800mg dose at 12 weeks, one endpoint was positive (p=0.0026) while the other three endpoints did not achieve statistical significance.

In the lower dose treatment arm, the 1200mg dose at 4 weeks achieved statistical significance in three of the four co-primary endpoints. Frequency was significantly reduced in both clinical trials (p-values of 0.0024 and 0.0117) at four weeks. Severity was significantly reduced in only one trial (p-value 0.0016). Of the other four co-primary endpoints of the 1200mg dose at 12 weeks, one endpoint was positive (p=0.0024) while the other three endpoints did not achieve statistical significance.

The primary endpoints in the studies were a statistically significant reduction in the frequency and severity of menopausal hot flashes relative to placebo after 4 weeks and 12 weeks of stable treatment. Both patients' and clinicians' impression of overall improvement in the higher dose treatment arm was highly statistically significant relative to placebo in both studies.

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.

Serada was generally well tolerated in both BREEZE trials. The most common adverse events were dizziness and somnolence. The incidence of dizziness in the active arms was between 17% and 24% (compared to 3% for placebo). Somnolence ranged from 7% to 19% in the active arms (compared to 2% or 3% in the placebo arms).