Clinical Trials

Date: 2016-07-15

Type of information: Results

phase: 2b

Announcement:

Company: Alder Biopharmaceuticals (USA - WA)

Product: ALD403

Action mechanism:

• monoclonal antibody. ALD403 is a genetically engineered monoclonal antibody that inhibits calcitonin gene-related peptide (CGRP), for prevention of migraine. CGRP is a small protein with a well-established role in the initiation, mediation, transmission and heightened sensitivity to pain experienced in migraine.
• ALD403 was discovered by Alder scientists and has been evaluated in multiple clinical trials evaluating approximately 800 patients. In a proof-of-concept clinical trial evaluating 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. ALD403 also has a favorable emerging safety profile, demonstrating a similar level of safety to placebo, and has been well-tolerated in studies to date.

Disease: chronic migraine

Therapeutic area: CNS diseases - Neurological diseases

Country:

Trial details: The Phase 2b clinical trial is a double-blind, placebo-controlled, randomized, single intravenous infusion, dose-ranging study in patients with chronic migraine. Patients were randomized 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 primary efficacy endpoint of the study is the change in migraine days between ALD403 and placebo as determined by the 75% responder rates over a 12-week period. Secondary endpoints include evaluations at week 24 and at week 48 (end of study).

Latest news:

• • On July 25, 2016, Alder BioPharmaceuticals announced top-line 24-week data demonstrating persistent migraine prevention in a Phase 2b clinical trial evaluating ALD403 in patients with chronic migraine.  In March 2016, Alder reported that the Phase 2b study met both the primary efficacy endpoint, a 75% reduction in migraine days over 12 weeks, and the secondary efficacy endpoint of mean reduction in migraine days from baseline.
• The 24-week data confirm and extend the 12-week data reported previously, including the 75% reduction in migraine days over 12 weeks and the mean reduction in migraine days from baseline, the primary efficacy and secondary endpoints, respectively.
• ALD403 demonstrated a persistent migraine preventative effect: The 75% responder rate for the entire 24 weeks at the 300 mg, 100 mg and 30 mg dose levels was 31%, 29% and 30%, respectively, compared to a placebo rate of 20%. ALD403 also demonstrated a persistent mean reduction in migraine days from baseline throughout the 24 week period. The 10 mg dose continued to be sub-therapeutic. The 10 mg 75% responder rate for the entire 24 week period was 20% compared to the placebo rate of 20%. The safety profile was consistent with the 12-week data reported previously and earlier ALD403 clinical trials. There were no new safety findings. The statistical analysis plan for the Phase 2b trial does not provide for analyses of statistical significance at time points post the primary endpoint at 12 weeks.
• Additional results, including future analysis of additional secondary endpoints and other data, are expected to be presented at upcoming medical meetings and published in peer reviewed medical journals. Alder expects that these additional results will further inform the dose selection and design of PROMISE 2.
• Endpoints will also be evaluated at week 48, which will mark the end of study.
• In March 2016, Alder reported that the 300 mg and 100 mg dose levels met the primary efficacy endpoint of the study, a 75% reduction in migraine days over 12 weeks in 33% and 31% of patients, respectively. A single administration of ALD403 also resulted in an immediate and durable mean reduction in migraine days from baseline throughout the 12 weeks at the 300 mg, 100 mg and 30 mg dose levels, meeting the secondary efficacy endpoint.

Is general: Yes