Bocunebart Reduced Monthly Migraine Days in Phase 2b PROCEED Trial
KEY TAKEAWAYS
- The intravenous portion of the phase 2b PROCEED trial met its primary efficacy end point, with bocunebart associated with a statistically significant reduction in monthly migraine days compared with placebo over weeks 1 to 12.
- Pooled phase 2 analyses in participants with chronic migraine showed greater reductions in migraine frequency, headache days, and migraine days with acute medication use among those treated with bocunebart vs placebo.
- No new safety signals were identified in PROCEED, and bocunebart was generally well tolerated across the phase 2 program.
Treatment with bocunebart (Lu AG09222; Lundbeck, Valby, Denmark) was associated with reduced monthly migraine days (MMDs) compared with placebo in the intravenous (IV) portion of the phase 2b PROCEED clinical trial (NCT06323928). The data from PROCEED were presented at the 2026 American Headache Society Annual Scientific Meeting. Bocunebart is an investigational ligand-targeting monoclonal antibody directed against pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide implicated in migraine pathophysiology through a pathway distinct from calcitonin gene-related peptide (CGRP).
PROCEED is a randomized, double-blind, placebo-controlled, adaptive phase 2b trial evaluating bocunebart for migraine prevention in adults aged 18 to 65 years with a history of migraine and 1 to 4 prior preventive treatment failures in the preceding 10 years. The analysis also included pooled data from HOPE (NCT05133323), a phase 2a proof-of-concept trial of bocunebart, to assess outcomes among participants with chronic migraine across the phase 2 program. The IV part of PROCEED included 257 participants treated with bocunebart and 172 participants treated with placebo. At baseline, mean MMDs were 13 in the bocunebart group and 13.7 in the placebo group; approximately half of participants had chronic migraine.
PROCEED Efficacy Results
In the IV portion of the trial, bocunebart dose A was associated with a mean change from baseline in MMDs of –4.24 over weeks 1 to 12 compared with –2.86 with placebo, for a difference of –1.38 days (P=.0178). Other IV doses did not show statistically significant differences vs placebo, with mean differences of –0.41 days for dose B (P=.4773) and –0.62 days for dose C (P=.2834).
Across the PROCEED and HOPE phase 2 program, pooled post hoc analyses included 696 participants treated with bocunebart and 414 participants treated with placebo. Among participants with chronic migraine, bocunebart was associated with greater reductions than placebo in MMDs, monthly headache days, and MMDs with acute medication use. Improvements were also reported in Migraine-Specific Quality of Life Questionnaire domains, including daily functioning, activity limitation, and emotional impact.
Safety outcomes were consistent across the phase 2 program. Treatment-emergent adverse events occurred in 37.7% of participants treated with bocunebart and 32.7% of those treated with placebo. Serious adverse events were reported in 0.7% of participants in each group. Treatment-emergent adverse events leading to withdrawal occurred in 1.4% of bocunebart-treated participants and 0.2% of placebo-treated participants. No deaths were reported. The most common adverse events occurring in at least 3% of participants in any treatment group were nasopharyngitis, injection-site erythema, and upper respiratory tract infection.
Based on the positive PROCEED findings and broader phase 2 data, further clinical development of bocunebart in migraine prevention is being planned. Bocunebart remains investigational and has not been approved by the Food and Drug Administration.
Source
Ailani J, Phul R, Florea I, Krog Josiassen M, Nitschky Schmidt S, Ashina M. Targeting PACAP in migraine prevention: outcomes from the PROCEED phase 2b trial of bocunebart (Lu AG09222). Presented at: American Headache Society Annual Scientific Meeting; June 4-7, 2026; Orlando, FL. Poster T110.