The FDA-submitted investigational monoclonal antibody tested well at 120 mg and 300 mg.
Two doses of monoclonal antibody galcanezumab have demonstrated efficacy, safety, tolerability for the preventive treatment of migraines, according to the results of a phase 2b randomized trial involving 400-plus patients.
Calcitonin gene-related peptide (CGRP) inhibitor galcanezumab, a member of a novel class of migraine prophylaxes, was tested for its benefits on adult patients who suffer from migraines versus placebo.
Researchers from Eli Lilly and Company — the manufacturer which received a Biologics License Application (BLA) approval from the US Food and Drug Administration (FDA) for the drug last week — led the 3-month treatment study.
Of the 936 patients assessed from the clinics of 37 licensed physicians, 410 were chosen to be randomly assigned placebo (137) or 4 different subcutaneous doses of galcanezumab monthly: 5 mg (68), 50 mg (68), 120 mg (70), or 300 mg (67).
Patients who met criteria for the study were between 18 and 65 years old, with 4 to 14 migraine headache days (MHDs) per month, and migraine onset prior to 50 years old. Researchers tested for migraine prevention as measured by the mean change from baseline in the number of patient MHDs 9 to 12 weeks following randomization.
MHDs and headache information data was collected separately from routine physician office visits for check-up and treatment administration. Participating patients called into an outcome interactive voice response system (ePRO) to record daily information.
The 120 mg galcanezumab dose met primary objective in patients, reaching a posterior probability of MHD improvement greater than 95% (99.6%; -4.8 MHDs, 90% BCI, -5.4 to -4.2 MHDs) versus placebo (-3.7 MHDs, 90% BCI, -4.1 to -3.2 MHDs).
Patients to have taken 120 galcanezumab also reported a mean statistically significant change of MHDs from baseline during the 3-month treatment period (-4.3 MHDs; 95% CI, -4.9 to -3.7; P = .02) versus placebo (-3.4 MHDs; 95% CI, -3.8 to -2.9 MHDs). The only other treatment group to report a statistically significant change was the 300 mg group (-4.3 MHDs; 95% CI, -4.9 to -3.7; P = .02).
In a measuring of functional impact — as gauged by Migraine-Specific Quality of Life Questionnaire (MSQ) and Headache Impact Test-6 (HIT-6) — owed to monthly migraine headaches, galcanezumab significantly improved patients versus placebo.
Researchers noted the long-term safety of CGRP-inhibitor monoclonal antibodies — of which there are currently 4 being developed for the preventive treatment of migraine — is currently unknown. The phase 2b study’s efficacy and safety results should be regarded as preliminary, they wrote, as the number of patients is insufficient to uncover rare or uncommon serious adverse effects.
That said, the results advocated for more consideration.
“Physicians and patients are seeking more effective and better tolerated treatments for migraine prevention than those currently approved and prescribed, researchers wrote. “These results provided sufficient efficacy, tolerability, and safety data to justify further development of galcanezumab, 120 mg and 240 mg, in larger phase 3 clinical trials.”
Expansive, phase 3 research into both of those dose rates were included in Eli Lilly’s BLA application to the FDA. The application included 3 studies (EVOLVE-1, EVOLVE-2, and REGAIN) that evaluated the safety and efficacy of once-monthly subcutaneous 120 mg and 240 mg galcanezumab for the prevention of migraine, following a 240 mg starting dose, in nearly 3,000 patients.
In both the EVOLVE-1 and EVOLVE-2 studies, patients with episodic migraine treated with galcanezumab 120 mg and 240 mg doses experienced a significant decrease in the average number of monthly MHDs versus placebo throughout a 6-month treatment period. Significant improvements were observed at each month.
Throughout the REGAIN study’s 3-month treatment period, patients with chronic migraine treated with galcanezumab 120 mg and 240 mg doses experienced a statistically greater decrease in the average number of monthly MHDs versus placebo.
Wei-Li Shao, vice president, US Lilly Neurosciences, told MD Magazine that galcanezumab is the first of the company’s 3 investigational, non-opioid therapies in development for their pain portfolio.
“For many people, the impact of migraine can be all-encompassing — a person may miss work, family activities or social engagements," Shao said. "Of the approximately 40% of all patients with migraine who are eligible for preventive therapy, only 13% are currently taking preventive medications. As such, millions of patients suffering from migraine are losing at least 1 month per year to migraine."
The study, "Effect of Different Doses of Galcanezumab vs Placebo for Episodic Migraine Prevention," was published online in JAMA Monday.