January 30, 2017

TherapeuticsMD issued results of a phase III trial of TX-001HR for the treatment of moderate to severe vasomotor symptoms (VMS) due to menopause in post-menopausal women with an intact uterus. The Replenish trial evaluated four doses of TX-001HR and placebo in 1,835 post-menopausal women between 40 and 65 years old. The doses studied were: 17ß-estradiol 1mg/progesterone 100mg (n=416), 17ß-estradiol 0.5mg/progesterone 100mg (n=423), 17ß-estradiol 0.5mg/progesterone 50mg (n=421), 17ß-estradiol 0.25mg/progesterone 50mg (n=424) and placebo (n=151). TX-001HR estradiol 1mg/progesterone 100mg and TX-001HR estradiol 0.5mg/progesterone 100mg both achieved all four of the co-primary efficacy endpoints and the primary safety endpoint, and a statistically significant and clinically meaningful reduction from baseline in both the frequency and severity of hot flashes compared to placebo. TX-001HR estradiol 0.5mg/progesterone 50mg and TX-001HR estradiol 0.25mg/progesterone 50mg were not statistically significant at all of the co-primary efficacy endpoints. The incidence of consensus endometrial hyperplasia or malignancy was 0% across all four TX-001HR doses. As outlined in the FDA guidance, the co-primary efficacy endpoints in the Replenish trial were the change from baseline in the number and severity of hot flashes at weeks four and 12 as compared to placebo. The primary safety endpoint was the incidence of endometrial hyperplasia with up to 12 months of treatment. General safety was also evaluated. The trial demonstrated a dose response favoring the higher doses of estradiol in combination with progesterone. The availability of multiple doses of TX-001HR would allow for individualized therapy to meet the needs of a diverse population of women. Additional efficacy and safety analyses of the Replenish trial data are ongoing. The company will continue to evaluate the data, and will submit a New Drug Application for TX-001HR to the FDA as early as the third quarter of 2017. 

September 26, 2011

Pfizer reported results from a phase III trial of bazedoxifene/conjugated estrogens (BZA/CE) for menopausal symptoms. This double-blind, placebo-controlled study, SMART-5 (Selective estrogens, Menopause, And Response to Therapy), enrolled 1,843 postmenopausal women who had not had a hysterectomy. The subjects received BZA/CE, CE/ medroxyprogesterone acetate (MPA), and BZA monotherapy or placebo in the following daily oral doses: BZA 20 mg/CE 0.45 mg, BZA 20 mg/CE 0.625 mg, BZA 20 mg, CE 0.45 mg/MPA 1.5 mg or placebo. One of the key primary endpoints was the incidence of endometrial hyperplasia at the end of one year of treatment. Results indicated that BZA 20 mg/CE 0.45 mg and BZA 20 mg/CE 0.625 mg demonstrated less than one percent incidence of endometrial hyperplasia over 12 months. A second key primary endpoint, the prevention of postmenopausal osteoporosis was also reached, as were the secondary endpoints of bone mineral density, breast density, sleep parameters and health-related quality of life.

September 5, 2011

Bionovo reported results from a phase I trial of Menerba for the treatment of menopausal hot flashes. This open-label, randomized trial (MF101-008) was designed evaluate Menerba at higher doses than tested in previous phase II trials. A total of 35 postmenopausal women between the ages of 40 and 65 years were enrolled in the trial. The primary goal was to assess the safety of the two doses of MF101 after four weeks of treatment. There were no reported cases of serious adverse events, no abnormal findings on endometrial biopsies, no abnormal lab results, and no changes to blood pressure, heart rate or weight. The subjects who were enrolled to the trial had an average number of 73 weekly hot flashes at baseline. After four weeks at these higher doses, the reduction in moderate to severe hot flashes was approximately 70% (p≡0.003). In addition, there was a 68% reduction in the number of nighttime awakenings due to hot flashes (p≡0.001).

June 28, 2010

Radius issued positive results from a phase IIa trial of RAD1901 for the treatment of menopausal hot flashes. This double-blind, placebo-controlled, dose-ranging study enrolled 100 healthy menopausal women experiencing recurrent moderate-to-severe hot flashes. The subjects received one of four doses of RAD1901 (10, 25, 50 or 100 mg) or placebo once daily over a four-week treatment period. The primary endpoint was the reduction in frequency and severity of hot flashes relative to baseline. Overall, the lowest dose of RAD1901 tested (10 mg) showed the greatest benefit compared to placebo and relative to the other dose groups studied. This dose achieved a statistically significant 77% reduction in frequency of moderate and severe hot flashes at week four relative to baseline, compared with 54% for placebo (p<0.05). The percent change in mean daily severity of hot flashes from baseline was -37% for RAD1901 (10mg) compared with -31% for placebo. The mean percent change in hot flash composite score (frequency plus severity) from baseline was -76% for RAD1901 (10mg) compared with -56% for placebo.

October 19, 2009

DepoMed issued positive results from two phase III trials of Serada, a non-hormonal extended release formulation of gabapentin, for the treatment of menopausal hot flashes. These randomized, double-blind, placebo-controlled studies, BREEZE-1 and BREEZE-2, enrolled a total of 1,100 subjects who received Serada 1200mg dosed once daily, Serada 1800mg twice daily (dosed 600mg in the morning and 1200mg in the evening) or placebo. The treatment duration in BREEZE-1 was six months and the treatment duration in BREEZE-2 was three months. The four co-primary efficacy 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. In the higher dose treatment arm, all four co-primary endpoints demonstrated significant reductions in frequency and severity in both clinical trials at four weeks (p-values ranged from 0.0001 to 0.004). 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, statistical significance was reached in three of the four co-primary endpoints at four weeks. 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). At 12 weeks, one endpoint was positive (p&equiv0.0024) while the other three endpoints did not achieve statistical significance.

July 11, 2005

Antares Pharma reported positive results of their phase III trial of Bio-E-Gel, their transdermal estradiol gel based on their Advanced Transdermal Delivery platform, for the treatment of hot flashes in menopausal women. The drug was seen to produce significant, dose-dependent reductions in both the number and severity of hot flashes, compared to placebo. No significant safety or tolerability concerns were raised for any dose. This randomized, double-blind, placebo-controlled study enrolled 484 symptomatic menopausal women suffering moderate to severe hot flashes, who received one of 3 doses of the drug or placebo for 12 weeks. Antares announced that, based on these data, they planned to submit an NDA to the FDA as soon as possible, hopefully by the end of September 2005.

Nymox issued positive combined results of a phase I and phase II trials of NX-1207, for the treatment of benign prostatic hyperplasia (BPH). The drug reduced mean symptom severity scores by 6.87 points on the American Urological Association BPH symptom severity scale, vs. a reduction of 0.5 points for controls (p<0.05). Statistically significant reductions in mean prostate size were also observed, and 2-year post-treatment follow-up indicated continued, increased superiority to placebo (9.3 points relative symptom improvement). Serious adverse events or tolerability concerns were not noted. These trials investigated NX-1207 as a first line therapy for men with BPH, and these trial data served to support ongoing phase II studies of the drug, expected to be completed later in 2005.

May 12, 2003

BioSante Pharmaceuticals reported positive results from a phase II/III trial investigating Bio-E-Gel (estradiol), a topical gel for the treatment of hot flushes in menopausal women. Results demonstrated that Bio-E-Gel effectively reduced the severity and frequency of moderate-to-severe hot flushes, according to FDA guidance for development of estrogen products. In addition, data showed that Bio-E-Gel delivered estradiol evenly over time without significant fluctuations in blood levels, such as those typically associated with hormone tablets. The randomized, double blind, placebo-controlled study of 161 symptomatic menopausal women was conducted in the U.S. and Canada. The objective of the trial was to identify an effective dose of Bio-E-Gel to study in Phase III development. Bio-E-Gel was applied daily to the same site with minimal skin irritation observed. Of the 161 women in the trial, only four experienced a brief episode of mild irritation.