Galcanezumab vs Rimegepant: First Head-to-Head Trial of New CGRP Antagonists Now Enrolling

Participant enrollment has opened for the CHALLENGE-MIG clinical trial (NCT05127486), which will be the first clinical trial to evaluate 2 calcitonin gene-related peptide (CGRP) antagonist drugs in a head-to-head manner for preventive treatment of episodic migraine in adults. The study will evaluate once-monthly galcanezumab (Emgality; Eli Lilly, Indianapolis, IN) compared to the every-other-day orally dissolving tables of rimegepant (Nurtec; Biohaven Pharmaceuticals, New Haven, CT) for prevention of episodic migraine. Target enrollment is 700 individuals.

Outcome measures will include reductions in monthly migraine headache days (MMD) and quality-of-life improvement. The primary endpoint is 50% or more reduction from baseline in monthly migraine headache days (MMD) across the 3-month, double-blind treatment period. Secondary endpoints include 75% or more and 100% reduction from baseline in MMD and improvements in the Migraine-Specific Quality of Life (MSQ) and Migraine Disability Assessment (MIDAS) tests.

"Lilly's CHALLENGE-MIG study will help us understand how different types of preventive medications (CGRP mAbs vs. gepants) may help people achieve the goals that matter most to them,” said Shivang Joshi, MD, MPH, RPh, neurologist, Dent Neurologic Institute. It's exciting that insights generated in this first-of-its-kind, head-to-head trial will be able to spark treatment plan discussions between people with migraine and their health care providers." 

The most common adverse reactions (incidence ≥2% and at least 2% greater than placebo) in clinical studies of galcanezumab were injection site reactions. WIth rimegepant, the most common adverse event was nausea. Hypersensitivity reactions, including dyspnea, urticaria, and rash, have occurred with galcanezumab in clinical studies and the postmarketing setting. Cases of anaphylaxis and angioedema have also been reported in the postmarketing setting. Hypersensitivity reactions, including dyspnea and rash, have also occurred with rimegepant in clinical studies and postmarketing, and these can occur days after administration and may be serious. 

Galcanezumab and rimegepant have similar mechanisms of action, in that both block the function of the CGRP receptor. However, the medicines are fundamentally different as galcanezumab is a monoclonal antibody (mAb) with a long half-life (weeks), different binding kinetics, and different metabolism. Rimegepant is small molecular antagonist of the CGRP receptor, metabolized through different pathways than antibodies and with a shorter half-life (hours). 

CHALLENGE-MIG is a randomized, placebo-controlled phase 4 study in adult patients who meet the International Classification of Headache Disorders-3 (ICHD-3) criteria for a diagnosis of migraine with or without aura and experience 4-14 migraine headache days per month.