CHALLENGE-MIG, a 3-month study, is the first trial to compare the efficacy of 2 previously approved calcitonin gene-related peptide antagonists in the treatment of migraine.
Newly announced topline findings from the CHALLENGE-MIG trial (NCT05127486), the first head-to-head clinical study comparing 2 medications targeting calcitonin gene-related peptide (CGRP), revealed similar efficacy between galcanezumab (Emgality; Eli Lilly) and rimegepant (Nurtec ODT; Biohaven Pharmaceuticals). Despite this, galcanezumab outperformed Rimegepant on secondary end points at the end of the 3-month trial.1
Eli Lilly will disclose the full results of CHALLENGE-MIG later this year. Comprised of 580 individuals with migraine, the study used a 50% reduction in monthly migraine headache days as the primary end point. Secondary end points of the trial include greater than 75% and 100% reduction from baseline in monthly migraine days and improvements in the Migraine-Specific Quality of Life (MSQ), a 14-item questionnaire designed to measure migraine-specific health-related quality of life by assessing the limitation of daily performance, and the Migraine Disability Assessment (MIDAS), a 5-item questionnaire used to assess headache-related disability in the past 3 months.
"These results bolster our knowledge of Emgality's ability to work quickly and help patients improve their quality of life with less frequent dosing," Anne White, executive vice president at Eli Lilly, and president of Lilly Neuroscience, said in a statement.1 "Reducing the frequency of migraine headache days can help people experience more freedom from the burden of this debilitating neurological disease and get back to participating in the daily activities that matter most to them."
Announced in July 2021, study participants were randomly assigned to either 4 injections of galcanezumab 120 mg or 45 doses of rimegepant 75 mg, both of which are the regulatory approved doses. Also, patients assigned to galcanezumab received placebo, and patients assigned to rimegepant received placebo injections.
Galcanezumab, a monoclonal antibody, binds to the CGRP protein, preventing it from attaching to the CGRP receptors, whereas rimegepant blocks the receptor for this protein. Originally approved as a preventive treatment of migraine in 2018, galcanezumab had its indication expanded a year later to include the treatment of episodic cluster headache. Since its original approval, galcanezumab remains the only CGRP monoclonal antibody that includes response rates of at least 50%, 75%, and 100% reduction in monthly migraine headache days in patients with episodic migraine in its FDA-approved labeling.
"Despite being the third most common disease worldwide, migraine remains largely under-diagnosed and under-treated,” Peter Goadsby, MD, PhD, MBBS, director of NIHR Clinical Research Facility, King’s College London, said in a statement.1 "I applaud Lilly for embarking on this bold study and their continued investment in the migraine community to better inform care. These results reinforce the impact that innovative medicines can have in the prevention of migraine."
In May 2021, rimegepant became the first medication approved for both acute and preventive therapy for migraine after originally joining the market as sole an acute treatment. The decision was made based on supporting data from the pivotal phase 3 clinical trial, known as Study 305. Those data showed that rimegepant decreased monthly migraine days by 4.3 days per month at month 3, compared with the placebo group’s 3.5-day reduction (P <.05). Additionally, of those in the rimegepant group, 49.1% reported at least a 50% reduction from the baseline number of moderate to severe migraine days compared to 41.5% in the placebo group.2
Prior to CHALLENGE-MIG, there was a matching-adjusted indirect comparison analysis conducted by Popoff et al that assessed the efficacy of galcanezumab against rimegepant. When matched to the EVOLVE trials (NCT02614183 and NCT02614196; galcanezumab vs placebo; n = 1773), rimegepant was superior to placebo, with a mean difference in monthly migraine day change from baseline of –1.16 (95% CI, –1.80 to –0.52) and was not statistically significantly different from galcanezumab (0.59 [95% CI, –0.13 to 1.32]). Rimegepant also showed superior MIDAS and MSQv2 results compared with placebo in both EVOLVE trials and in the STRIVE trial (NCT02456740; erenumab vs placebo; n = 955), no statistically significant differences from galcanezumab and erenumab (Aimovig; Amgen/Novartis), another FDA-approved medication, regarding MIDAS.3