Migraine (Adult)

June 18, 2018

Allergan announced positive results from CGP-MD-01, a Phase IIb/III clinical trial evaluating the efficacy, safety, and tolerability of orally administered atogepant. Study CGP-MD-01 is a Phase IIb/III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. The primary efficacy endpoint was the change from baseline in mean monthly migraine/probable migraine (MPM) headache days across the 12-week treatment period. All active treatment arms of atogepant met the primary endpoint across all doses and dose regimens, with a statistically significant reduction from baseline in monthly migraine/probable migraine (MPM) headache days in patients with episodic migraine treated with atogepant compared with placebo for 12 weeks. In study CGP-MD-01 834 U.S. adult patients were randomized (2:1:2:1:2:1) to placebo, 10-mg QD, 30-mg QD, 30-mg BID, 60-mg QD, and 60-mg BID respectively, and treated under double blind conditions 12 weeks for the prevention of episodic migraine. Efficacy analyses were based on the modified ITT (mITT) population of 795 patients. All active treatment groups demonstrated a statistically significant reduction from baseline in the primary efficacy parameter (10 mg QD vs placebo, p=0.0236; 30 mg QD vs placebo, p=0.0390; 60 mg QD vs placebo, p=0.0390; 30 mg BID vs placebo; p=0.0034, 60 mg BID vs placebo, p=0.0031). The most common adverse events were nausea, fatigue, constipation, nasopharyngitis, and urinary tract infection.

May 7, 2018

Allergan announced positive results from ACHIEVE II (UBR-MD-02), the second of two pivotal Phase III clinical trials evaluating the efficacy, safety and tolerability of orally administered ubrogepant 25 mg and ubrogepant 50 mg compared to placebo in a single migraine attack in adults. The ACHIEVE II study included 1,686 U.S. adult patients randomized (1:1:1) to placebo, ubrogepant 25 mg and 50 mg respectively, to treat a single migraine attack of moderate-to-severe headache intensity. In the modified ITT (mITT) population of 1,355 patients, 18 to 75 years of age with a history of migraine, both doses showed a statistically significant greater percentage of ubrogepant patients achieving pain freedom at two hours after the initial dose as compared to placebo patients (25 mg vs placebo, p=0.0285, 50 mg vs placebo, p=0.0129). The ACHIEVE II trial is a Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy, safety and tolerability of two doses of ubrogepant (25 mg and 50 mg) compared to placebo for the treatment of a single migraine attack.

February 12, 2018

Allergan announced positive results from ACHIEVE I (UBR-MD-01), the first of two pivotal phase III clinical trials evaluating the efficacy, safety and tolerability of orally administered ubrogepant 50 mg and ubrogepant 100 mg compared to placebo in a single migraine attack in adults. The ACHIEVE I study included 1327 U.S. adult patients randomized (1:1:1) to placebo, ubrogepant 50 mg and 100 mg respectively, who were treated for a single migraine attack of moderate to severe headache intensity. The ACHIEVE I trial is a Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. The co-primary efficacy parameters were pain freedom (PF) at two hours after the initial dose and absence of the most bothersome migraine-associated symptom (photophobia, phonophobia or nausea) at two hours after the initial dose. Both doses showed a statistically significant greater percentage of ubrogepant patients achieving pain freedom at two hours after the initial dose as compared to placebo patients (50 mg vs placebo, p=0.0023, 100 mg vs placebo, p=0.0003) and a statistically significant greater percentage of ubrogepant patients achieving absence of the most bothersome migraine-associated symptom at two hours after the initial dose as compared to placebo patients (50 mg vs placebo, p=0.0023, 100 mg vs placebo, p=0.0023). Ubrogepant was well tolerated with an adverse event profile similar to placebo. The most common adverse events were nausea, somnolence, and dry mouth, none of which were reported with a frequency of ≥5 percent.F

January 29, 2018

Amgen reported positive results from the Phase IIIb LIBERTY study assessing the efficacy and safety of Aimovig (erenumab) 140mg in patients with episodic migraine who had experienced two to four previous preventive treatment failures, due to lack of efficacy or intolerable side effects. The multicenter, randomized 12-week, double-blind, placebo-controlled study enrolled 246 participants. The study includes an ongoing 52-week open-label extension study. The study met its primary endpoint, with significantly more patients taking Aimovig experiencing at least a 50 percent reduction from baseline in their monthly migraine days as compared to placebo. LIBERTY also met all secondary endpoints, including reduction of monthly migraine days, reduction in days needing acute (rescue) medication, improvement in scores on the Migraine Physical Function Impact Diary (MPFID) tool, and 75 percent and 100 percent responder rates (number of patients experiencing at least a 75 percent or 100 percent reduction in monthly migraine days compared to placebo). The safety data are consistent with previous studies of Aimovig to date. The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of May 17, 2018.

January 15, 2018

Alder BioPharmaceuticals announced that eptinezumab, its lead investigational product candidate for migraine prevention targeting calcitonin gene-related peptide (CGRP), met the primary endpoint in its pivotal Phase III PROMISE 2 clinical trial with very high statistical significance vs. placebo (p<0.0001) for both dose levels tested in the trial following a single quarterly infusion. In addition, eptinezumab met all key secondary endpoints with very high statistical significance vs. placebo including prevention beginning Day One (p<0.0001) and 50 percent (p<0.0001) and 75 percent (p<0.0001) responder rates month one through month three. Furthermore, 15 percent of eptinezumab patients had no migraines (i.e., 100 percent response) for a full three months (p<0.0001 unadjusted). Safety and tolerability were similar to previously reported eptinezumab studies. The observed safety profile in this study, to date, is consistent with previously reported eptinezumab studies. Adverse event rates among eptinezumab-treated subjects were similar to placebo-treated subjects. Commonly reported adverse events for eptinezumab, occurring at an incidence of 2.0 percent or greater, were nasopharyngitis (common cold) (6.3 percent), upper respiratory infection (4.0 percent), nausea (3.4 percent) and urinary tract infection (3.1 percent), arthralgia (joint pain) (2.3 percent), dizziness (2.6 percent), anxiety (2.0 percent) and fatigue (2.0 percent). If approved by the FDA, eptinezumab will be the first-to-market migraine prevention infusion therapy, with 100 percent of the treatment dose available upon administration. 

September 18, 2017

Eli Lilly reported results of a phase III study of galcanezumab for migraine. In the 12-month, open-label study, 270 patients were randomized to treatment with galcanezumab 120mg or galcanezumab 240mg. Galcanezumab was associated with a statistically significant reduction in the number of monthly migraine headache days with both doses (5.6 days for 120mg and 6.5 days for 240mg, p<0.001 for both dosing groups). Notably, there was no clinically meaningful difference in the rate of adverse events between galcanezumab 120mg and 240mg dosing groups. The most commonly reported adverse events (≥10%) in both dosing groups included injection site pain, nasopharyngitis and upper respiratory tract infection. Serious adverse events were reported by three patients in the 120mg dosing group and seven patients in the 240mg group. Lilly plans to submit a Biologics License Application (BLA) to the FDA for galcanezumab in the second half of 2017, followed by submissions to other regulatory agencies around the world.

July 3, 2017

Alder BioPharmaceuticals issued results of a phase III study of eptinezumab for frequent episodic migraine. PROMISE 1 was a double-blind, randomized, placebo-controlled study evaluating eptinezumab (300mg, 100mg or 30mg) administered by intravenous infusion once every 12 weeks through week 24. PROMISE 1 met the primary endpoint: highly statistically significant reductions in monthly migraine days. Significant Day 1 clinical benefit was a ≥50% reduction in the proportion of patients experiencing a migraine on Day 1 post-dose. There were significant 75% responses at all key time points: ~1/3 of patients achieved a ≥75% reduction in migraine days through four and 12 weeks. An average of one in five patients had 100% response: no migraines in any given month, months one through six. Enrollment is on track for PROMISE 2, a second pivotal phase III study that focuses on chronic migraine, and the company is on track to submit a BLA with the FDA in 2018.

June 19, 2017

Eli Lilly released results from three phase III studies of galcanezumab for the prevention of episodic and chronic migraine. In the EVOLVE-1 and EVOLVE-2 studies, over the six-month treatment period, patients with episodic migraine treated with galcanezumab 120mg and 240mg doses experienced a statistically significantly greater decrease in the average number of monthly migraine headache days compared to patients treated with placebo, with statistically significant improvements observed at each month starting at one month of treatment. A statistically significantly greater percentage of patients treated with both doses of galcanezumab achieved at least a 50%, 75% and 100% reduction in the number of migraine headache days compared to placebo over the six-month treatment period, in both studies after multiplicity adjustment. In the REGAIN study, over the three-month treatment period, patients with chronic migraine treated with galcanezumab 120mg and 240mg doses experienced a statistically significantly greater decrease in the average number of monthly migraine headache days compared to patients treated with placebo. Statistically significant improvements for both doses of galcanezumab were observed at each month starting at one month of treatment. A statistically significantly greater percentage of patients also achieved at least a 50% reduction in the number of migraine headache days compared to placebo over the three-month treatment period (27.6% for 120mg and 27.5% for 240mg compared to 15.4% for placebo, p<0.001 for both dosing groups) after multiplicity adjustment. Based on these results, Lilly will submit a Biologics License Application to the FDA for galcanezumab in the second half of 2017, followed by submissions to other regulatory agencies around the world.

June 5, 2017

Teva Pharmaceutical Industries announced positive results from a phase III HALO study of fremanezumab, an investigational treatment for the prevention of migraine. In the chronic migraine (CM) study, patients treated with fremanezumab experienced statistically significant reduction in the number of monthly headache days of at least moderate severity vs. placebo (-2.5 days) during the 12 week period after first dose, for both monthly (-4.6 days p<0.0001) and quarterly (-4.3 days p<0.0001) dosing regimens. Similar to the Phase II trials, both patients that were on monotherapy and stable doses of prophylactic medications were included in the trial. In addition, patients treated with fremanezumab experienced significant improvement compared to placebo on all secondary endpoints for both monthly and quarterly dosing regimens, including: response rate, onset of efficacy, efficacy as monotherapy, and disability. The results were positive, and of 13 hierarchical comparisons, p was <0.0001 in 12 of them, being 0.0004 in the remaining. The most commonly-reported adverse event in the study was injection site pain, with similar rates in the placebo and active groups. Based on these results, Teva plans to submit a Biologics License Application to the FDA for fremanezumab later this year.

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