Numerous anticipated clinical milestones
Our pipeline includes three internally discovered humanized monoclonal antibodies (including one preclinical monoclonal antibody), as well as preclinical programs targeting additional indications that are in the discovery phase.
ALD403 is our investigational monoclonal antibody targeted to calcitonin gene-related peptide, or CGRP, for migraine prevention. CGRP is 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.
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 ALD403 significantly reduced the number of days on which the study subjects experienced migraines. In our Phase 2 proof-of-concept trial, 27-41% of 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 three month study period. In our Phase 2b clinical trial, 33% and 31% of chronic migraine patients dosed with 300 mg and 100 mg, respectively, of ALD403 experienced a 75% decrease in their migraines from an average of 16 or more migraine days per month. We are encouraged by these results and believe that, with the possibility of offering the convenience of two modes of administration, ALD403 has the potential to be a best-in-class therapeutic.
- The primary and key secondary efficacy endpoints were met in an ongoing double blind, randomized, placebo-controlled Phase 2b of ALD403 in patients with 15 or more headache days a month, at least 8 of which are migraines, or chronic migraine. Results were presented at the American Headache Society 58th Annual Scientific Meeting in June 2016 (view presentation or read the press release) and at the 5th European Headache and Migraine Trust International Congress in September 2016 (view poster or read the press release). The following additional data supporting the development of ALD403 were also presented both at the June 2016 AHS and September 2016 EHMTIC: the results of a comparative pre-clinical case study of ALD403 and other CGRP antibodies (view poster); and the results of our Multiple-Dose, Phase 1 Placebo-Controlled, Randomized Study of ALD403, An Anti-CGRP Antibody, Administered Every 3-Months via IV, SC, or IM (view poster).
- We have completed a double blind, randomized, placebo-controlled, Phase 2 proof-of-concept trial of ALD403 in patients suffering from 5 to 14 migraine days per month, or high-frequency migraine. These positive results were presented at the 56th Annual Scientific Meeting of the American Headache Society in June 2014 and at the American Academy of Neurology (AAN) Annual Meeting in May 2014. View the trial results or read the press release.
- At the 17th Congress of the International Headache Society in May 2015, we presented positive six-month follow-up data from our Phase 2 proof-of concept clinical trial. The data show that a single IV dose of ALD403 demonstrated continued efficacy over six months for the preventive treatment of migraine; 11 percent of patients were migraine-free for the entire six-month follow-up period. Read the press release.
- We have initiated the first of two planned pivotal trials, PROMISE 1 (PRevention Of Migraine via Intravenous ALD403 Safety and Efficacy 1), a 600-patient double-blind, randomized, placebo-controlled, multi-dose trial. We are evaluating three dose levels of ALD403 and placebo administered quarterly in patients living with frequent episodic migraine. In 2016, we plan to initiate the second pivotal trial, PROMISE 2 (PRevention Of Migraine via Intravenous ALD403 Safety and Efficacy 2), a double-blind, randomized, placebo-controlled, multi-dose trial. We plan to study two dose levels of ALD403 and placebo administered quarterly to patients living with chronic migraine. The primary endpoint for both trials is the change in migraine days between ALD403 and placebo as determined by the difference in responder rates over a 12-week period.
- We have 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 ALD403 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. View the trial results or read the press release.
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. Read the press release.
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.