Lundbeck's Bocunebart Meets Primary Endpoint in Phase IIb Migraine Prevention Trial
Lundbeck's investigational anti-PACAP antibody bocunebart demonstrated statistically significant reduction in monthly migraine days versus placebo in a phase IIb trial of patients who had failed prior preventive treatments, positioning the company for phase III discussions with regulators.
H. Lundbeck A/S announced positive results from the intravenous part of its phase IIb PROCEED trial, with investigational migraine prevention treatment bocunebart (Lu AG09222) meeting its primary endpoint. The trial demonstrated a statistically significant difference to placebo in the change from baseline in the number of monthly migraine days over weeks 1 to 12 in a population that experienced past treatment failures.
The PROCEED trial enrolled 431 patients from 14 countries including Bulgaria, Czechia, Denmark, France, Georgia, Germany, Hungary, Lithuania, Japan, Poland, Romania, Slovakia, Spain, and the United States. The target population was defined as patients diagnosed with migraine as outlined in the International Classification of Headache Disorders Third Edition (ICHD-3) and with treatment failure of 1-4 different preventive migraine medications in the past 10 years. The trial assessed the efficacy, safety, and tolerability of bocunebart versus placebo when administered once monthly for three months.
Bocunebart was generally well tolerated, and no new safety signals were detected during the PROCEED trial. The coordinating investigator stated that the efficacy demonstrated in this trial represents a promising advancement in the treatment of migraine, offering hope to many patients suffering from this debilitating condition.
The results build on findings from the previously successful HOPE phase IIa trial evaluating single IV administration of bocunebart. That study demonstrated that 32% of patients in the 750mg bocunebart group saw a reduction of at least 50% in the number of migraine days per month, compared with 27% of those on placebo. The number of headache days per month reduced by 5.8 days in the higher dose group compared with 4.1 days in the placebo group.
Additional analyses will be done to better understand the dose-response relationship across the investigated doses. Based on this positive outcome, Lundbeck will approach regulatory authorities to discuss the results and phase III design options. The trial results are planned to be presented at an upcoming conference and submitted for scientific publication at a later date.
Bocunebart is an investigational monoclonal antibody with a novel mechanism of action. It is engineered to bind to and inhibit the signaling of pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide implicated in migraine pathophysiology. This mechanism operates through a pathway distinct from that targeted by anti-calcitonin gene-related peptide (anti-CGRP) therapies. Bocunebart represents a potential new treatment class and could provide an alternative option for migraine prevention.
The PROCEED trial aimed to establish the optimal dose and route of administration, subcutaneous and IV, of bocunebart. Lundbeck discontinued development of the subcutaneous formulation in 2025 after prespecified interim analysis showed the therapy was unlikely to succeed. The company is now focusing exclusively on the intravenous version.
The broader PACAP landscape has seen multiple failures in recent years. Amgen's drug, AMG 301, saw no benefit in a phase II trial, and Eli Lilly terminated the development of its candidate LY3451838 after a phase II trial. A key difference with bocunebart is that it targets the ligand rather than a specific receptor, allowing it to work across three separate receptors implicated in the PACAP pathway (PAC1, VPAC1, and VPAC2).
Lundbeck acquired bocunebart, originally ALD1910, when it purchased Alder BioPharmaceuticals for up to $1.95 billion (approximately €1.8bn at the time) in 2019. The company already markets an IV CGRP inhibitor administered every three months, Vyepti (eptinezumab), which has been growing strongly, with sales up more than 50% to DKK 4.48 billion ($711 million) last year.
Migraine is a complex and incapacitating neurological disease characterized by recurrent episodes of moderate to severe, pulsating headaches typically accompanied by an array of symptoms, including nausea, vomiting, and sensitivity to light and sound. As the most prevalent neurological disorder in people aged under 50 years, migraine imposes both a social and financial burden, affecting around 135 million people in the G7 countries plus China. The migraine market is expected to reach $16.4 billion across the seven major markets (US, France, Germany, Italy, Spain, UK, and Japan) in 2033, up from $9.2 billion in 2023.