zelminemab (AMG 301) / Amgen, Novartis - LARVOL DELTA

Pituitary adenylate-cyclase activating polypeptide (PACAP)-targeting treatment as a potential migraine prophylactic therapy (PubMed, Ideggyogy Sz) - "Results from a Phase 2a randomized clinical trial using a human mAb against the PAC1 receptor (subcutaneous AMG 301) showed no difference between placebo and the active drug in reducing the number of monthly migraine days (MMD)...A recently published Phase 2 clinical trial investigating a human mAb targeting PACAP (a single 1500 mg intravenous dose of LY3451838) showed no difference in the reduction of MMDs in patients with episodic and chronic migraine. The results of the ongoing PROCEED study, which evaluates the efficacy of four different doses of Lu AG09222 in migraine prevention, are expected to be published soon. Based on the findings from early-phase observations with mAbs against PACAP and its receptor, further high-phase clinical studies are required."

Clinical • Journal • Review • CNS Disorders • Migraine • Pain • ADCYAP1

From CGRP to PACAP, VIP, and Beyond: Unraveling the Next Chapters in Migraine Treatment. (PubMed, Cells) - "Clinical studies have demonstrated the significance of PACAP in migraine pathophysiology; however, a few clinical trials remain inconclusive: the pituitary adenylate cyclase-activating peptide 1 receptor mAb, AMG 301 showed no benefit for migraine prevention, while the PACAP ligand mAb, Lu AG09222 significantly reduced the number of monthly migraine days over placebo in a phase 2 clinical trial. In light of recent advances in PACAP research, we emphasize the potential of PACAP as a promising target for migraine treatment, highlighting the significance of exploring PACAP as a member of the antimigraine armamentarium, especially for patients who do not respond to or contraindicated to anti-CGRP therapies. By updating our knowledge of PACAP and its unique contribution to migraine pathophysiology, we can pave the way for reinforcing PACAP and other secretin peptides, including VIP, as a novel treatment option for migraines."

Journal • Review • CNS Disorders • Migraine • Pain • ADCYAP1

Targeting pituitary adenylate cyclase-activating polypeptide (PACAP) with monoclonal antibodies in migraine prevention: a brief review. (PubMed, Expert Opin Investig Drugs) - "We discuss and critically evaluate (i) the evidence of the role of PACAP in migraine pathophysiology and (ii) the first clinical trials in migraine prophylaxis with monoclonal antibodies AMG 301 and ALD1910 which act against PAC1 and PACAP38 respectively. Theoretically, if these antibodies block the activation of the trigeminovascular system, they will prevent the onset of migraine attacks. There are still knowledge gaps in the role of PACAP in migraine and the risk/benefit ratio of anti-PACAP antibodies must be carefully studied."

Journal • CNS Disorders • Migraine • ADCYAP1

Study to Evaluate the Efficacy and Safety of AMG 301 in Migraine Prevention (clinicaltrials.gov) - P2a; N=343; Completed; Sponsor: Amgen; Active, not recruiting ➔ Completed

Clinical • Trial completion