Robust development pipeline
Our pipeline includes three internally discovered humanized monoclonal antibodies, as well as preclinical programs targeting additional indications that are in the discovery phase.
Eptinezumab is our lead pivotal-stage investigational product candidate being developed as a migraine prevention treatment for patients with chronic and frequent episodic migraine. Eptinezumab, discovered by Alder, is a novel monoclonal antibody that inhibits the calcitonin gene-related peptide, or CGRP, a small protein involved in the transmission of, and heightened sensitivity to, pain experienced in migraine.
Migraine is a significant cause of disability worldwide, generally affecting individuals between the ages of 20 and 50, which are peak productive years. The Migraine Research Foundation estimates U.S. employers lose more than USD$13 billion each year as a result of 113 million lost workdays due to migraine. A preventive therapy for these patients is a critical unmet medical need, as they have few therapeutic options.
Eptinezumab Clinical Data
Data from our Phase 2 proof-of-concept trial in patients with frequent episodic migraine and from our Phase 2b clinical trial in patients with chronic migraine established that a single administration of eptinezumab significantly reduced the number of days in which the study patients experienced migraines. In each of these studies, we observed a rapid onset and sustained 12-week migraine prevention after a single treatment with eptinezumab.
- In our Phase 2 proof-of-concept trial, 27-41% of frequent episodic migraine patients experienced complete migraine-free relief, that is 100% suppression of migraine occurrence, in any given month and migraines were completely prevented in 16% of patients for the entire 12 week study period. View results
- In our Phase 2b clinical trial, 33% and 31% of chronic migraine patients dosed with 300 mg and 100 mg, respectively, of eptinezumab experienced a 75% decrease in their migraines over the 12 week study period from an average of 16 or more migraine days per month. In addition, a single administration of eptinezumab resulted in an immediate and durable mean reduction in migraine days from baseline throughout the 12 weeks at the 300mg, 100mg and 30mg dose levels, meeting the secondary efficacy endpoint. View results
We have also completed a multi-dose, placebo-controlled, randomized, quarterly-dosing Phase 1 study comparing the intravenous, subcutaneous and intramuscular routes of administration in healthy volunteers. The study demonstrated that eptinezumab provided a comparable level of suppression of peripheral CGRP biology for a full 3 months when administered via a single intravenous (100 mg), subcutaneous (100 mg) or intramuscular injection (100 mg or 300 mg), supporting a quarterly dosing strategy as a single injection by all modes of administration.
Eptinezumab Pivotal Trial Program
The eptinezumab pivotal trial program includes three Phase 3 trials:
- PROMISE 1 (PRevention Of Migraine via Intravenous ALD403 Safety and Efficacy 1) is an 800-patient double-blind, randomized, placebo-controlled, multi-dose trial. The study is evaluating the safety and efficacy of three dose levels of eptinezumab versus placebo, administered by infusion once every 12 weeks for one year in patients living with frequent episodic migraine. Completion of PROMISE 1 enrollment was announced in October 2016.
- PROMISE 2 (PRevention Of Migraine via Intravenous ALD403 Safety and Efficacy 2) is a 1,050-patient double-blind, randomized, placebo-controlled, multi-dose trial. This study is evaluating the safety and efficacy of two dose levels of eptinezumab versus placebo, administered by infusion once every 12 weeks in patients living with chronic migraine. Initiation of PROMISE 2 was announced in November 2016.
- An open-label extension study is evaluating the long-term safety and tolerability of eptinezumab. This study will enroll approximately 120 patients that will receive eptinezumab administered by infusion every 12 weeks for one year. It was initiated in late 2016.
The primary endpoint for PROMISE 1 and PROMISE 2 is the mean reduction in migraine days from baseline over weeks 1-12. Key secondary endpoints for PROMISE 1 and PROMISE 2 are the 75% responder rate over weeks 1 to 12 as determined by the change in migraine days between eptinezumab and placebo, and the 75% responder rate over weeks 1 to 4 as determined by the change in migraine days between eptinezumab and placebo.
Clazakizumab is a novel monoclonal antibody that inhibits the pro-inflammatory cytokine interleukin-6, or IL-6. Clazakizumab has been administered in clinical trials involving over one thousand patients, and has demonstrated positive results in Phase 2b trials evaluating patients with rheumatoid arthritis and psoriatic arthritis. Alder licensed the exclusive worldwide rights to clazakizumab to Vitaeris Inc. which will pursue innovative therapeutic indications in chronic inflammatory diseases.
ALD1910 is a genetically engineered monoclonal antibody discovered and designed by Alder to specifically inhibit pituitary adenylate cyclase-activating peptide-38, or PACAP-38, a protein active in mediating the initiation of migraine. We believe ALD1910 holds potential as a migraine prevention treatment for those who have an inadequate response to therapeutics directed at calcitonin gene related peptide, or CGRP, and could provide an important new therapeutic option to migraine patients and their physicians.
ALD1910 is currently undergoing Investigational New Drug (IND) enabling preclinical studies. Similar to our other internally developed product candidates, ALD1910 is designed to have favorable antibody properties and a desirable product profile we consider critical to a streamlined development path.