Positive top-line efficacy data for migraine prevention drug ALD403 pushed Alder Biopharmaceuticals Inc. shares (NASDAQ:ALDR) 50 percent higher to $25.70 by Monday market close, bolstering the company's standing in a race to bring the first calcitonin gene-related peptide (CGRP) receptor antagonist to what's expected to be a multibillion-dollar market. Teva Pharmaceutical Industries Ltd., Amgen Inc. and Eli Lilly and Co. are also developing drugs in the space.
The new data, from an ongoing phase IIb trial, "represent not only the largest reported study of an anti-CGRP antibody in chronic migraine, but also the first time that any of the anti-CGRP antibodies have demonstrated efficacy in patients with chronic migraine using established FDA-approvable endpoints," Alder CEO Randy Schatzman said during a conference call held to discuss the results.
One-third of patients receiving a 300-mg dose of the intravenous (I.V.) drug and nearly a third of those who got a 100-mg dose experienced a statistically significant 75 percent reduction in migraine days each month during the 12-week study period that Alder detailed from the study. While safety data are still blinded, Alder said the safety profile appeared to be consistent with earlier trials of the therapy.
The Bothell, Wash.-based company estimates that 13 million patients with migraine may be candidates for preventive therapy, of which about 3 million have chronic migraine, defined as those experiencing 15 or more headache days per month, of which eight or more are assessed as migraines.
Patients in the double-blind, placebo-controlled study were randomized to receive a single I.V. infusion of 10 mg, 30 mg, 100 mg or 300 mg of the monoclonal antibody or placebo, with about 120 patients per group. The primary efficacy endpoint is the change in migraine days between ALD403 and placebo as determined by the 75 percent responder rates over a 12-week period. Endpoints will also be evaluated at week 24, with an expected readout during the third quarter, and at week 48, the end of the study.
In addition to the phase IIb data, on Monday Alder also presented data from a phase I quarterly dosing study demonstrating that 100-mg and 300-mg doses provided for a full three months of suppression of peripheral CGRP biology independent of route of administration, whether via I.V. (100 mg), subcutaneous (100 mg) or intramuscular (100 mg or 300 mg) routes in healthy volunteers.
Schatzman called that "a compelling observation" that "further bolsters our strategy of quarterly dosing via intravenous infusion or via self-administration and gives us solid confidence that we can utilize the phase I pharmacodynamic data to closely dial in the dosing profile to carry forward for self-administration studies."
Later this year, Alder plans to initiate PROMISE 2 (PRevention Of Migraine via Intravenous ALD403 Safety and Efficacy 2), its second pivotal study in patients with chronic migraine. The company is also working toward delivery of top-line data from PROMISE 1, its ongoing pivotal trial in patients with frequent episodic migraine, in 2017.
If approved, Alder plans to commercialize ALD403 on its own in the U.S. and potentially with a partner in Europe and Asia. The therapy would compete with beta-blockers that are approved for prevention of frequent episodic and chronic migraine such as propranolol, marketed by Pfizer Inc., and other treatments such as topiramate, marketed by Johnson & Johnson, and sodium valproate. In addition, Botox (onabotulinumtoxinA), marketed by Allergan plc, is approved for the prevention of chronic migraine and is commonly prescribed for frequent episodic migraine, according to Alder.
Furthermore, Alder said in its latest annual filing with the SEC, "even though not as effective in treating high-frequency and chronic migraine, patients may be satisfied using cheaper generic abortive medications such as triptans, which could limit ALD403 market penetration in the migraine prevention marketplace."
Alder could also face competition from other CGRP-inhibiting therapies in development, including Amgen's AMG-334, Lilly's LY-2951742 and the Teva candidate LBR101/PF-04427429 (sourced from Labrys Biologics Inc.), all of which are using antibodies similar to ALD403. (See BioWorld Today, June 4, 2014, and Aug. 7, 2014.)
"I'm not one to score [front-runners]," Alder CEO Schatzman told BioWorld Today in 2014. Analysts, of course, are another story: "All four late-stage competitors appear to have relatively similar efficacy," Leerink analyst Jason Gerberry wrote in a note to clients. What will more likely differentiate them, he said, is safety and tolerability; ease of administration; order of entry and commercialization strategy. "From a Teva perspective, we continue to view [the] CGRP category as [a] $4 billion to $6 billion category that will be divided equally among the four late-stage competitors, pending further pivotal-stage data."
Alder, which was founded in 2002, has yet to generate any product revenue, but it has raised a significant amount of money. Through Dec. 31, its operations have been primarily funded by $486.9 million of net proceeds in public offerings, $111.4 million in private placements of convertible preferred stock and $135 million in up-front payments, milestones and R&D payments from collaborators. The company had accumulated a deficit of $222.4 million at Dec. 31 and had $381 million in cash and cash equivalents, short-term and long-term investments. (See BioWorld Today, June 29, 2015.)