Positive results have been reported from a phase 2b study of ALD403 (Alder BioPharmaceuticals), a monoclonal antibody product candidate for migraine prevention that targets calcitonin gene-related peptide (CGRP). Patients with chronic migraine demonstrated that ALD403 prevented migraine during the entire 12-week study period, meeting both primary and secondary efficacy endpoints.
In the double-blind, placebo-controlled, randomized, dose-ranging study, patients with chronic migraine were randomly assigned to receive a single intravenous infusion of 10 mg, 30 mg, 100 mg, or 300 mg of ALD403 or placebo (approximately 120 patients per group). The study’s primary efficacy endpoint was the change in migraine days between ALD403 and placebo, as determined by the 75% responder rates over a 12-week period.
Chronic migraine is defined as 15 or more headache days per month, of which at least eight must be assessed as migraine days.
The 100-mg and 300-mg doses of ALD403 met the primary efficacy endpoint in 31% and 33% of treated patients, respectively (P < 0.05).
A single administration of ALD403 resulted in an immediate and durable mean reduction in migraine days throughout the 12 weeks of treatment at 300 mg (P < 0.01), 100 mg (P < 0.01), or 30 mg (P < 0.05), meeting the secondary efficacy endpoint. In addition, a single administration of ALD403 at 300 mg, 100 mg, or 30 mg demonstrated a durable reduction in migraine days for the entire 12 weeks, supporting a quarterly dosing strategy. The 10-mg dose of ALD403 was identified as subtherapeutic.
ALD403 is a genetically engineered monoclonal antibody that inhibits CGRP, a small protein involved in the initiation, mediation, and transmission of and heightened sensitivity to pain experienced in migraine. ALD403 has been evaluated in approximately 800 patients. In a proof-of-concept clinical trial in patients with frequent episodic migraine, ALD403 demonstrated significant prevention of migraines, including complete migraine relief (100% suppression of migraine occurrence) in 27% to 41% of patients in any given month. Migraines were completely prevented in 16% of patients for the entire three-month study period.
The Migraine Research Foundation (MRF) estimates that 36 million American adults and children experience migraines. According to the American Migraine Foundation (AMF), migraine is three times more common in women than in men and affects 30% of women over a lifetime. The MRF estimates that U.S. employers lose more than $13 billion each year as a result of 113 million lost work days due to migraine.
Currently, preventive medications approved for migraine include beta blockers (such as propranolol), topiramate, sodium valproate, and botulinum toxin (Botox). The adverse effects of these medications, such as cognitive impairment, nausea, fatigue, and sleep disturbance, often limit their use, according to the AMF. The U.S. Agency for Healthcare Research and Quality has reported that only about 12% of adults with frequent episodic or chronic migraine take preventive medications.
Source: Alder BioPharmaceuticals; March 28, 2016.