[Pituitary adenylate-cyclase activating polypeptide (PACAP)-targeting treatment as a potential migraine prophylactic therapy].

BACKGROUND AND PURPOSE: In migraine prophylaxis, specific therapeutic options are provided by monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) and its receptor, CGRP receptor antagonists (gepants), and 5-hydroxytryptamine 1F receptor agonist ditans. mAbs acting on the pituitary adenylate cyclase-activating polypeptide (PACAP) or its receptor (PAC1) represent a new therapeutic target.

METHODS

A literature review based on a PubMed search.

RESULTS

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). The HOPE study (Phase 2) targeted PACAP as a ligand used low (100 mg) and high (750 mg) doses of an intravenous humanized mAb, Lu AG09222, in patients with episodic and chronic migraine. After 4 weeks of treatment, the reduction in MMDs from baseline was -6.2 days in the high-dose active group, compared to -4.2 days in the placebo group. 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.

CONCLUSION

Based on the findings from early-phase observations with mAbs against PACAP and its receptor, further high-phase clinical studies are required.