Investigational Migraine Preventive ALD1910 Doses First Phase 1 Patient

October 14, 2019

Alder Biopharmaceuticals announced the dosing of the first patient with ALD1910, its investigational monoclonal antibody that inhibits PACAP to prevent migraine. The study is aiming to enroll 100 individuals with results in mid-to-late 2020.

Bob Azelby, MBA

The first patient has been dosed in a phase 1 study of an investigational monoclonal antibody for the preventive treatment of migraine, Alder BioPharmaceuticals’ ALD1910, the company has announced.1

ALD1910 is an inhibitor of pituitary adenylate cyclase-activating polypeptide (PACAP), an important signaling molecule in the pathophysiology of migraine which literature suggests may play a similar role to calcitonin gene-related peptide (CGRP) in its contribution to disease.2 Enrollment for the study is expected to include 100 healthy individuals between ages 18 and 55 years, to assess the safety, tolerability and pharmacokinetic profile of ALD1910 at various doses. Results are expected in the latter half of 2020.

“More than 70% of the 14 million people with migraine who experience more than four headache days per month are not being treated with preventive therapies,” Bob Azelby, president and chief executive officer, Alder BioPharmaceuticals, said in a statement. “We believe that no single treatment mechanism is going to benefit every person living with this disease. ALD1910 has the potential to provide a new mechanism-specific therapeutic approach for people with migraine and their physicians.”

In April, Azelby told NeurologyLive that the company was “very excited” about the agent and that it “expect[s] to be first-in-human with ALD1910 by the end of 2019—the end of this year.”

“We’re excited that that may be another opportunity because as excited as we are about eptinezumab and its unique clinical profile, we’re helping out about 6 out of 10 patients. That means 4 out of 10 patients are not getting relief. We see ALD1910 as an opportunity to help those patients, and it’s just reiterating that we’re early on in this migraine disease and understanding it, so there’s still a lot of opportunity for innovation,” he told NeurologyLive.

ALD1910 has shown reactivity to PACAP38, through the PAC1, VPAC1, and VPAC2 receptors, as well as PACAP27. Literature also suggests the agent blocks the cell0surface binding of a nonlinear epitope within PACAP.3

“PACAP is an attractive pathway in addressing migraine and the preclinical work has been very encouraging as it demonstrated ALD1910 prevents the signaling of PACAP with all three known receptors,” said Paul Streck, MD, chief medical officer, Alder, in a statement. “There is excitement among the medical community to assess the clinical potential of ALD1910 to possibly help patients who may require a different approach for the prevention of migraine.”

Alder is also expected to bring its CGRP inhibitor, eptinezumab, onto the market in early 2020. In April, the FDA accepted a biologics license application from Alder for the treatment, with supporting data coming from the PROMISE 1 and PROMISE 2 clinical trials, along with an open-label safety study and pharmacokinetic data. The therapy is an intravenous (IV) quarterly infusion that studies suggest achieves 100% bioavailability after the 30-minute infusion it is administered in.

According to Azelby, the PROMISE 2 data—in which 60% and 33% of patients who averaged 16 migraines per month at baseline dropped to ≤8 migraines or ≤4 migraines per month after treatment, respectively—is the key to displaying eptinezumab’s efficacy.

REFERENCES

1. Alder BioPharmaceuticals® Announces First-in-Human Dosing in Phase 1 ALD1910 Study for Preventive Treatment of Migraine [press release]. Bothell, WA: Alder BioPharmaceuticals; Published October 10, 2019. investor.alderbio.com/news-releases/news-release-details/alder-biopharmaceuticalsr-announces-first-human-dosing-phase-1. Accessed October 11, 2019.

2. Kaiser EA, Russo AF. CGRP and migraine: Could PACAP play a role too? Neuropeptides. 2013;47(6):451-461. doi: 10.1016/j.npep.2013.10.010.

3. Loomis CM, Dutzer B, Ojala EW, et al. Pharmacologic Characterization of ALD1910, a Potent Humanized Monoclonal Antibody against the Pituitary Adenylate Cyclase Activating Peptide. J Pharmacol Exper Thera. 2019;369(1):26-36. doi: 10.1124/jpet.118.253443.