Lundbeck’s migraine drug hits phase II goal, though IV-only path narrows commercial prospects

Bocunebart met its primary endpoint, demonstrating a statistically significant reduction in monthly migraine days compared to placebo over 12 weeks in 431 patients across 14 countries who had failed between one and four previous preventive treatments. The monoclonal antibody was generally well-tolerated and no new safety signals emerged during the dose-finding trial, Lundbeck said in a statement. The company noted that full data would be presented at an unspecified upcoming conference and published in a scientific journal.

“These data underline Lundbeck’s ambition to deliver the first PACAP targeting option in migraine prevention,” Dr. Johan Luthman, Lundbeck’s Head of Research & Development, said in the press release. “With its novel mechanism of action, it has the potential to become an important addition to the migraine treatment paradigm, furthering Lundbeck’s mission to improve outcomes for people living with severe migraine.”

A rocky path to positive data

Bocunebart, originally ALD1910, was developed by Alder BioPharmaceuticals before Lundbeck acquired the company for up to $1.95 billion (approximately €1.8bn at the time) in 2019. The drug targets pituitary adenylate cyclase-activating polypeptide (PACAP). PACAP is a neuropeptide implicated in migraine through a pathway distinct from the calcitonin gene-related peptide (CGRP) system underpinning subcutaneous preventive therapies currently on the market.

The antibody previously showed proof of concept in the phase IIa HOPE trial, where a single IV infusion at 750 mg demonstrated efficacy. This stirred up hopes that a subcutaneous dosing might also show statistically-significant results, though these were dashed last year when Lundbeck scrapped that arm of the PROCEED trial after enrolling 75% of its cohort of patients.

“The initial news is disappointing that the sub-q formulation is sub-optimal, and that the company is moving to an IV-based formulation,” said Leerink Partners analysts in a note to investors at the time.

Targeting the ligand rather than the receptor

Lundbeck’s persistence is notable because the broader PACAP landscape is littered with failures. US competitors Amgen and Eli Lilly both scrapped their antibody candidates after failed trials in recent years, creating jitters among analysts and investors. 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).

While limiting, the constraints imposed by the IV formulation of the drug are unlikely to prevent its successful commercialization. Lundbeck’s CGRP-targeting competitor Vyepti is also administered intravenously, yet its sales soared last year. By the company’s own estimates, there are up to 3 million target patients in the G7 countries alone, whose treatment with other options, including CGRP therapies, has failed.

“The efficacy demonstrated in this trial represent[s] a promising advancement in the treatment of migraine, offering hope to many patients suffering from this debilitating condition,” the coordinating investigator of the trial, Dr. Jessica Ailani, added in Lundbeck’s release.