Lundbeck has reached a significant milestone in its Phase IIb PROCEED clinical trial for migraine prevention, announcing the expansion of the study to include intravenous (IV) administration of its investigational monoclonal antibody Lu AG09222, following a pre-specified interim analysis.
The biopharmaceutical company reported reaching 75% of its recruitment target in the subcutaneous (SC) dose-finding portion of the trial, triggering the planned expansion to explore IV dosing options. This development builds on positive findings from the previously successful HOPE Phase IIa trial that evaluated IV administration of the same compound.
Lu AG09222 represents a potentially groundbreaking approach to migraine prevention through its novel mechanism of action. The antibody is designed to bind and inhibit pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide implicated in migraine pathophysiology. This approach targets a pathway distinct from the calcitonin gene-related peptide (CGRP) pathway utilized by currently approved preventive treatments.
Addressing Significant Unmet Needs in Migraine Treatment
Despite recent advances in migraine therapeutics, a substantial treatment gap remains. An estimated 2.5 to 3.0 million patients across G7 countries experience inadequate relief from currently available preventive medications. Lu AG09222 could potentially become the first in its class for migraine prevention by targeting the PACAP pathway.
"The expansion of the PROCEED trial to include intravenous administration reflects our commitment to thoroughly exploring all potential delivery methods for this promising therapy," said a Lundbeck representative. "By leveraging our established IV clinical infusion infrastructure for migraine prevention, we aim to determine the optimal route of administration and dosing regimen."
PROCEED Trial Design and Patient Population
The PROCEED trial, initiated in March 2024, employs an adaptive design to evaluate both the efficacy and optimal delivery method of Lu AG09222. The study is being conducted across sites in Europe, Japan, and the United States.
The trial specifically targets patients diagnosed with migraine according to the International Classification of Headache Disorders Third Edition (ICHD-3) criteria who have experienced treatment failure with 1-4 different preventive migraine medications in the past decade. This focus on treatment-resistant patients addresses a critical gap in current migraine management.
The study's adaptive design consists of two parts:
- Part A: Subcutaneous administration dose-finding
- Part B: Intravenous administration dose-finding (now being initiated)
Participants receive either Lu AG09222 or placebo once monthly for three months, with researchers assessing efficacy, safety, and tolerability outcomes.
The Burden of Migraine
Migraine represents a significant global health burden as the most prevalent neurological disorder in people under 50 years of age. The condition affects approximately 135 million people across G7 countries and China, causing substantial disability and reduced quality of life.
The neurological disease is characterized by recurrent episodes of moderate to severe pulsating headaches, often accompanied by nausea, vomiting, and sensitivity to light and sound. Beyond the physical symptoms, migraine significantly impacts patients' family, social, and work lives, with many living in constant fear of the next attack.
Timeline and Future Directions
Lundbeck expects to complete the PROCEED trial in the first half of 2026, with plans to initiate pivotal Phase III studies in the second half of that year. The company can leverage its existing IV clinical infusion infrastructure established for migraine prevention to facilitate the expanded trial.
If successful, Lu AG09222 would offer a first-in-class treatment option targeting the PACAP pathway, potentially benefiting patients who have not responded adequately to existing preventive therapies, including those targeting the CGRP pathway.
The development of Lu AG09222 aligns with Lundbeck's focus on brain health and commitment to addressing complex neurological challenges, particularly for patients with limited or no treatment options.
