October 24, 2016
AbbVie issued results of two replicate pivotal phase III trials of Elagolix in premenopausal women who suffer from endometriosis. The first pivotal trial (M12-665) was a 24-week, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of Elagolix in 872 women, age 18 to 49, with moderate to severe endometriosis-associated pain. It was conducted at 175 sites in the U.S., Puerto Rico and Canada. The second trial (M12-671) employed the same design as the first trial, was multinational and included 815 women with moderate to severe endometriosis-associated pain across 226 sites in 13 countries (U.S. and 12 ex-U.S. countries). Together, these two studies evaluated the safety and efficacy of Elagolix in nearly 1,700 women. In the two studies, both doses of Elagolix administered orally demonstrated a statistically significant (p≤0.001) improvement versus placebo in the percentage of DYS and NMPP responders. In the first study, at month three, 46% of patients treated with 150mg once daily and 76% of patients treated with 200mg twice daily of Elagolix were classified as DYS responders, versus 20% of patients in the placebo group. Fifty percent of patients treated with 150mg once daily and 55% of patients treated with 200mg twice daily of Elagolix were classified as NMPP responders, versus 36% of patients in the placebo group. The second pivotal phase III study demonstrated similar results. The safety profile of Elagolix was consistent across both phase III trials and also consistent with prior Elagolix studies. Discontinuations due to AEs were 5.9% and 6.1% for placebo in study 1 and study 2, respectively, 6.4% and 4.4% for 150mg once daily in study 1 and study 2, respectively, and 9% and 10% for 200mg twice daily in study 1 and study 2, respectively.
September 19, 2016
Repros Therapeutics released results of a phase II study of Proellex for the treatment of premenopausal women with confirmed symptomatic endometriosis. The study was a double-blind study with endometriosis defined as a baseline BBSS Score (Biberoglu and Behrman Symptom Score) of seven or greater. Subjects were randomized to 6mg or 12mg of Proellex or placebo in a 1:1:1 fashion. The study randomized 60 subjects at a mean age of 30 years. The median percentage change from baseline in the patient BBSS assessment of menstrual pain showed that subjects improved with an 85.4% reduction in baseline score (p<0.0001). In addition, despite evidence of a placebo response, subjects treated with Proellex had a statistically significant greater reduction in menstrual pain compared to the 37.5% change from baseline achieved with placebo (p=0.0008). During this first course of treatment, subjects treated with Proellex experienced a 56% reduction in total pill count while placebo-treated subjects’ pill use declined by 30% (p=0.0521). The reduction in non-prescription use was significant: Proellex-treated subjects had a 74% reduction while placebo-treated subjects only experienced a reduction of 11% (p=0.0423). The company intends to discuss phase III trials with the FDA.
February 22, 2016
Neurocrine Biosciences issued results of the second of two replicate pivotal phase III clinical trials evaluating Elagolix in premenopausal women who suffer pain from endometriosis. The first phase III trial (M12-665) was a 24-week, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of Elagolix in 872 women, age 18 to 49, with moderate-to-severe endometriosis-associated pain. It was conducted at approximately 160 sites in the U.S., Puerto Rico and Canada. The second phase III trial (M12-671) employed the same design as the first phase III pivotal trial, but was multinational and included 815 women with moderate-to-severe endometriosis-associated pain across 226 sites in 13 countries. Trial results show that after six months of continuous treatment, both doses of Elagolix (150mg once daily and 200mg twice daily) met the study’s co-primary endpoints. Elagolix reduced scores of menstrual pain (dysmenorrhea, DYS) and non-menstrual pelvic pain (NMPP) associated with endometriosis, at month three and month six, as measured by the Daily Assessment of Endometriosis Pain scale. The safety profile of Elagolix in this study was consistent with observations from the first phase III pivotal study and prior Elagolix studies. Among the most common treatment-emergent adverse events (TEAEs) were hot flush, headache and nausea. As anticipated by the mechanism of action, some AEs, such as hot flush, other hypoestrogenic TEAEs and changes in bone mineral density (BMD) were dose-dependent. Overall discontinuation rates were similar across treatment groups (25.3%, 21.2% and 19.7% for placebo, 150mg once daily and 200mg twice daily, respectively); discontinuations specifically due to TEAEs were 6.1%, 4.4% and 10% for placebo, 150mg once daily and 200mg twice daily, respectively. AbbVie will complete the clinical database in anticipation of a New Drug Application submission for endometriosis in 2017.
February 9, 2015
AbbVie and Neurocrine Biosciences
issued results of the first of two ongoing
phase III trials of elagolix in pre-menopausal
women with endometriosis. The first
trial (M12-665) was a 24-week, randomized,
double-blind, placebo-controlled study
designed to evaluate the safety and efficacy
of elagolix in 872 women, age 18 to 49,
with moderate-to-severe endometriosis-associated
pain. Results from the trial show
after six months of treatment, both doses
of elagolix (150mg once daily and 200mg
twice daily) met the study’s co-primary
endpoints (p<0.001) of reducing scores
of non-menstrual pelvic pain (NMPP) and
menstrual pain (or dysmenorrhea) associated
with endometriosis, at month three, as
well as month six, as measured by the Daily
Assessment of Endometriosis Pain scale. The
observed safety profile of elagolix was consistent
with observations from prior studies.
Among the most common adverse events
(AEs) were hot flush, headache, nausea and
fatigue. Overall discontinuation rates were
similar across treatment groups and discontinuations
specifically due to AEs were 5.9%,
6.4% and 9.7% for placebo, 150mg once
daily and 200mg twice daily, respectively. A
second phase III, randomized, multinational,
double-blind, placebo-controlled trial
(M12-671) evaluating elagolix in patients
with moderate-to-severe endometriosis-related
pain is ongoing and results are
expected in late 2015.
May 31, 2010
Neurocrine Bioscience issued positive results from a phase II trial of elagolix for the treatment of endometriosis. This U.S-based, double blind, placebo controlled study, Daisy PETAL (901 study), enrolled 137 subjects who received elagolix 150 mg or placebo once daily for two months. The co-primary efficacy endpoints, the mean change from baseline for dysmenorrhea (pelvic pain during menstruation) and non-menstrual pelvic pain, were reached with statistical significance over placebo. A responder analyses was also conducted and revealed a clinically meaningful improvement of 30% or greater reduction from baseline for both scales. All secondary endpoints, including the Patient Global Impression of Change and the Composite Pelvic Signs and Symptoms Scale, were also reached with statistical significance over placebo.
April 6, 2009
Neurocrine Biosciences reported positive results from a phase II trial of elagolix for the treatment of endometriosis. This randomized, placebo-controlled study, dubbed (702/Lilac PETAL) enrolled 155 subjects who were placed into three treatment arms; elagolix 150 mg or 250 mg once daily, or placebo. After completion of the initial three months of treatment, placebo recipients were re-randomized to elagolix for an additional three months. The primary endpoint was an improvement in the pain and symptoms of endometriosis at three months. Symptoms of dysmenorrhea improved significantly in both elagolix treatment groups compared to placebo (elagolix 150 mg, p<0.01; elagolix 250 mg, p<0.001). Additionally, the percentage of dysmenorrhea pain-free days was higher in the elagolix treatment groups when compared to placebo (elagolix 150 mg, p≡0.0012; elagolix 250 mg, p≡0.0002). In addition, statistically significant improvement was seen for elagolix 150 mg (p< 0.05) and elagolix 250 mg (p<0.005) compared to placebo on the score of "worst pain" assessed on the numeric rating scale. Elagolix was found to be safe and well tolerated.
September 8, 2008
Neurocrine Biosciences issued positive results from a phase II trial of elagolix for the treatment for the treatment of endometriosis. This multicenter, randomized, double-blind, active-controlled study, dubbed PETAL, enrolled 252 subjects with a confirmed diagnosis of endometriosis. The subjects were placed into three treatment groups; elagolix 150 mg once daily, elagolix 75 mg twice daily, or depo-subQ provera 104 (standard of care), for six months of treatment. The primary endpoint was the percent change from baseline in mean bone mineral density (BMD) at month six, measured via dual energy X-ray absorptiometry. In women randomized to elagolix 150 mg once daily, the mean percent change from baseline at month six was -0.11% for the spine and -0.47% for the femur. The mean percent change from baseline at month six for the elagolix 75 mg twice daily dosing arm was -1.30% for the spine and -0.99% for the femur. The secondary endpoint was reached as well. Both doses of the drug had a clinically meaningful and significant reduction in endometriosis pain from baseline, which was comparable to that shown by depo-subQ provera 104. Treatment with elagolix was safe and generally well tolerated. Additional phase II trials are currently underway.
August 4, 2008
Repros reported positive interim results from a phase II trial of Proellex for the treatment of endometriosis. This double-blind trial enrolled 75 female subjects in the United States with moderately severe to severe endometriosis pain. The subjects received two oral doses of Proellex (25mg and 50mg) once-a-day or placebo for 16 weeks. The primary endpoint was the change in endometriosis symptom score, as measured by the Mean Endometriosis Symptom Severity Scale (MESSS). The baseline reported MESSS scores for subjects randomized to placebo, 25 mg or 50 mg Proellex were 7.3, 6.9 and 7.0 respectively. At the end of the first month of treatment, patient reported pain scores for placebo, 25 mg and 50 mg Proellex were 4.0, 2.2 and 2.6, respectively, indicating a 45% and 35% reduction in pain scores compared with placebo. At the end of the second month of treatment, reported scores for placebo, 25 mg and 50 mg Proellex were 4.50, 1.25 and 1.75, respectively, indicating a 72% and 61% reduction in pain scores compared with placebo. These reductions were statistically significant compared with placebo (Proellex 25 mg versus placebo p 0.0018, Proellex 50 mg versus placebo p 0.0064). There was no statistically significant difference between the Proellex 25 mg and 50 mg treatments at any time-point. Treatment was generally well tolerated. Based on the results Repros plans to continue with the trial as planned.
January 15, 2007
Neurocrine released positive preliminary results from a phase II trial of NBI-56418 for the treatment of endometriosis. This multi-center, randomized, double-blind, placebo-controlled trial enrolled 68 subjects who were randomized to one of three treatment groups: 50 mg or 100 mg of NBI-56418 or placebo, each administered twice daily. Treatment started on day 2 to day 7 of the menstrual cycle and continued over 12 weeks, with assessments of symptoms and signs of disease conducted at 4-week intervals. The primary endpoint, reduction in endometriosis symptoms, was evaluated using the Composite Pelvic Sign and Symptoms Score (CPSSS) and the Visual Analog Scale (VAS) measured pain intensity. Treatment was well tolerated, with adverse events similar across the groups. CPSSS, with a maximum value of 15, displayed mean values at baseline of 7.8 (placebo), 7.2 (50 mg) and 8.3 (100mg). After treatment there were reductions of 4.3 (placebo), 4.7 (50 mg) and 5.3 (100 mg) points in the score at week 12. The VAS scores at baseline were 73 (placebo), 68 (50 mg) and 72 (100 mg). Data revealed dose-related improvements in the maximum score, particularly at week 4 with reductions of 3 (placebo), 17 (50 mg) and 20 (100 mg). Based on the data, Neurocrine plans move the development of NBI-56418 forward.
Pherin revealed positive results from a phase II trial of intranasal PH80 for the treatment of Premenstrual Syndrome. This double blind, placebo-controlled trial enrolled 60 subjects who were randomized into one of two treatment groups: 800 nanograms of PH80 up to four times daily during six consecutive days or placebo. Treatment was well tolerated, with no reported adverse events. The primary endpoint, statistically significant improvement in PMS symptoms compared to placebo, was met, with 63% of the PH80 treated subjects showing an improvement versus 44% on placebo (p less than 0.05). Remission of symptoms one month after treatment also showed statistically significant improvement when compared to placebo (p less than 0.01) . Based on these results, Pherin was planning phase III trials to further evaluate PH80 in the treatment of Premenstrual Syndrome.
October 30, 2006
Repros Therapeutics issued positive preliminary data from a phase II trial of Proellex for the treatment of endometriosis. This trial enrolled 39 women in Europe, 16 of who had completed three months of dosing at this time. Subjects received three dose levels of Peoellex (12.5mg, 25mg, or 50mg) or Lupron, the current standard of care. A dose dependent effect on pain reduction appeared over the course of three months, with the women on the 50mg Proellex therapy showing the less than one day of pain, versus an average of 19.4 days of pain for those on Lupron. In addition, Luprin reduced estrogen concentrations to post-menopausal levels (less than 20 pg/ml) while all doses of Proellex maintained estrogen concentrations in the low normal range. Final results from this study are expected in December of 2006.
May 8, 2006
Neurocrine issued positive results of a phase II trial of their orally available GnRH antagonist NBI-56418, for the treatment of endometriosis. This randomized, double-blind, placebo-controlled multi-center study enrolled 76 subjects, who received one of 2 doses of the drug (75 mg or 150 mg) or placebo once daily for 12 weeks, starting on day 2 to day 7 of each subject's menstrual cycle. Trial data showed reductions in symptom severity score for all 3 dosing groups during the trial period, as measured on the Composite Pelvic Sign and Symptoms Score diagnostic scale at week 12 (-3.9 points for 75 mg NBI-56418 -5.0 points for 150 mg, vs. -3.7 points for placebo). Additional changes were noted on patient-reported visual analog scale with a 14 point improvement for the low dose and a 21 point improvement for the high dose, vs. a 5 point improvement for placebo. Based on these results the company announced plans to initiate a phase IIb trial of the drug in Q3 2006, which was to enroll several hundred patients.
May 17, 2004
AEterna Laboratories and Zentaris GmbH reported positive results from six phase II trials investigating cetrorelix, a luteinizing hormone releasing hormone antagonist for the treatments of benign prostatic hyperplasia (BPH), uterine myomas and endometriosis. The placebo-controlled endometriosis study demonstrated that cetrorelix was associated with a rapid response and improvement of endometriosis-related symptoms. Placebo-controlled uterine myoma trials demonstrated that subcutaneous administrations of cetrorelix demonstrated a reduction of myoma/uterine volume within one month. Results from two placebo-controlled BPH trials demonstrated a dose-dependent improvement in clinical symptoms, including IPSS (International Prostate Symptom Score) and maximum uroflow in the cetrorelix treatment group compared with the placebo group. Full results will be presented during the 18th World Congress of the International Federation of Fertility Societies in Montreal.
FemmePharma reported positive results from a phase II trial investigating FP1096, an intravaginally delivered drug for the treatment of endometriosis. Results showed that the primary efficacy endpoint, change in the Biberoglu and Behrman Symptom Score from baseline to treatment end, demonstrated a statistically significant decrease in symptoms. The multicenter, prospective, open-label study enrolled 30 subjects with endometriosis at four sites in the U.S. Secondary efficacy endpoints included a pain assessment questionnaire, a quality of life measure and a daily diary assessment. Results were reported at the 52nd Annual Clinical Meeting of The American College of Obstetricians and Gynecologists.
January 26, 2004
FemmePharma reported positive results from a phase II trial investigating FP1096, an intravaginally delivered drug for the treatment of endometriosis. Results demonstrated that FP1096 reduced the symptoms with very minimal side effects. The severity of symptoms were assessed using the Biberoglu and Behrman Symptom Score (BBSS). Data demonstrated a statistically significant decrease in BBSS indicating the subjects had a diminishment in the symptoms associated with endometriosis. The multicenter, prospective, open-label study will enroll 30 subjects at 4 sites in the U.S. Subjects were screened to assess their suitability and to ensure that they had moderate-to-severe endometriosis. The primary efficacy endpoint was change in BBSS from baseline to the end of treatment. Secondary efficacy endpoints were a pain assessment questionnaire, a quality of life measure and a daily diary assessment.
December 10, 2001
Positive results were reported from a phase I trial of Inhale Therapeutic Systems' inhaleable leuprolide, a peptide analog used to treat prostate cancer and endometriosis. Data showed that a powdered formulation of leuprolide developed with Inhale's Inhance pulmonary delivery technology administered the drug with a bioavailability of 18% (inhaleable versus injectable systemic delivery). In the 12-subject trial, the powdered leuprolide dose was packaged in a single capsule, and subjects inhaled the drug using a small dry powder inhaler.
The final results from a phase IIb trial of Valentis' interleukin-2 (IL-2) GeneMedicine product did not confirm positive interim findings. The randomized trial was designed to compare the IL-2 GeneMedicine product plus standard chemotherapy to standard chemotherapy alone in subjects with advanced head and neck cancer. The trial data demonstrated that the positive trend in the IL-2 treatment group versus the chemotherapy alone group was not sustained throughout the trial. The trial was conducted in collaboration with Roche Holdings.