Alder BioPharmaceuticals, announced that eptinezumab, its lead product candidate for migraine prevention, met the primary and key secondary endpoints in PROMISE 1, a Phase 3 pivotal clinical trial evaluating patients with frequent episodic migraine.
PROMISE 1 Highlights
- PROMISE 1 met the primary endpoint: highly statistically significant reductions in monthly migraine days;
- Significant Day 1 clinical benefit: ≥50% reduction in the proportion of patients experiencing a migraine on Day 1 post-dose;
- Significant 75% responses at all key time points: ~1/3 of patients achieved a ≥75% reduction in migraine days through 4 and 12 weeks;
- Average of 1 in 5 patients had 100% response: no migraines in any given month, months 1 through 6; and
- The safety profile was similar to placebo: consistent with previously reported eptinezumab studies.
“Approximately 13 million people suffer from the pain and debilitation of migraines that occur four or more days a month, yet nine out of 10 individuals don’t utilize preventive therapy due to limitations in efficacy, safety and tolerability,” said Roger Cady, MD, Alder Vice President of Neurology and Fellow of the American Headache Society. “Patients deserve more from their treatments, and these data show eptinezumab could be a major advance in meeting the significant unmet need for patients to regain control of their lives.”
PROMISE 1 Top-Line Results
The primary endpoint, demonstrating statistically significant reductions in monthly migraine days from baseline (average of 8.6 days) over weeks 1 through 12 was 4.3 monthly migraine days for 300mg (p=0.0001) and 3.9 days for 100mg (p=0.0179) compared to an average 3.2 days for placebo. A 30mg dose level evaluated in the study was not tested as per the statistical analysis plan.
Secondary endpoints evaluating time points through the first quarterly dose include:
- ≥75% reduction in monthly migraine days achieved over weeks 1 through 4 of 31.5% for 300mg and (p=0.0066), and 30.8% for 100mg (p=0.0112) compared to 20.3% for placebo.
- ≥75% reduction in monthly migraine days achieved over weeks 1 through 12 of 29.7% for 300mg (p=0.0007), and 22.2% for 100mg (not statistically significant) compared to 16.2% for placebo.
- ≥50% reduction in monthly migraine days achieved by 56.3% of patients over weeks 1 through 12 for 300mg (p=0.0001) and 49.8% for 100mg (p=0.0085, unadjusted) compared to 37.4% for placebo.
- 53.6% reduction in the proportion of patients experiencing migraine on the day following administration at 300mg (p=0.0087, unadjusted), and 51.3% at 100mg (p=0.0167, unadjusted), compared to 20.7% for placebo
Secondary endpoints demonstrated responses that were improved through the second quarterly dose period, and include:
- ≥75% reduction in monthly migraine days achieved over weeks 13 through 24 of 40.1% for 300mg (p=0.0006, unadjusted), and 33.5% for 100mg (p=0.0434, unadjusted) compared to 24.8% for placebo.
- Average of one in five patients receiving 300mg (20.6%) had 100% responses with no migraines in any given month (months 1 through 6).
The observed safety profile in this study to date was similar to placebo. Both the safety profile and the placebo rates were consistent with previously reported eptinezumab studies. Full safety data will be available at the end of the study.
“Alder’s goal is to discover and develop best-in-class therapies that have the potential to transform the lives of the millions of underserved patients who are seeking long-term freedom from their migraines,” said Alder President and Chief Executive Officer Randy Schatzman, Ph.D. “These positive results, consistent with previously reported eptinezumab studies, support the unique clinical profile of eptinezumab as a potential first-of-its-kind infusion therapy to prevent migraines. Enrollment is on track for PROMISE 2, our second pivotal Phase 3 study that focuses on chronic migraine, and we remain on track to submit our BLA with the U.S. Food and Drug Administration (FDA) in the second half of 2018.”
Migraine is a disabling neurological disease.1 Current preventive treatments for migraine are challenged by safety, efficacy, and tolerability limitations and fail to meet the needs of most patients.2,3 Migraine preventive treatments can take weeks to months to achieve meaningful clinical benefit and, subsequently, most patients discontinue within 6 months to 1 year due to lack of efficacy and/or side effects.3,4 The eptinezumab development program was designed to redefine physician and patient expectations for migraine prevention. This includes early, meaningful, sustained migraine prevention including the opportunity for patients to experience long periods of migraine freedom.
Filed Under: Drug Discovery