The phase 4 study will evaluate the efficacy and safety of once-monthly injectable galcanezumab compared with every-other-day rimegepant taken orally.
RESEARCH HAS SHOWN THAT raised blood and salivary levels of calcitonin gene-related peptide (CGRP) occur in patients with headache disorders, such as migraines and cluster headaches, as well as several neuralgias.1 The recent discovery of targeting the CGRP pathway has led to a number of new medications, including Eli Lilly’s galcanezumab (Emgality) and Biohaven Pharmaceuticals’ rimegepant (Nurtec ODT).
Announced in July 2021, CHALLENGE-MIG (NCT05127486) is the f irst head-to-head clinical trial comparing 2 medications targeting CGRP (TABLE). Galcanezumab, a monoclonal antibody (mAb), binds to the CGRP protein, preventing it from attaching to the CGRP receptors, whereas rimegepant blocks the receptor for this protein. The hope is that findings from this multisite, randomized, double-blind, double-dummy, parallel-group phase 4 study may help clinicians and patients make more informed treatment decisions.
The trial opened enrollment in November 2021 and is expected to enroll approximately 700 adults with episodic migraine. The primary end point will be a 50% reduction in monthly migraine headache days for up to 6 months of treatment. Those with a diagnosis of episodic migraine with or without aura will be treated with either 120-mg galcanezumab once-monthly injection with an initial 240-mg loading dose, or 75-mg rimegepant taken every other day.2
Galcanezumab was FDA approved in September 2018 as a preventive treatment for migraine in adults and since then, remains the only CGRP mAb that includes response rates of at least 50%, at least 75%, and 100% reduction in monthly migraine headache days in patients with episodic migraine in its FDA-approved labeling. On the other hand, in May 2021, rimegepant became the first medication approved for both acute and preventive therapy for migraine after originally joining the market as solely an acute treatment.
When enrollment was announced, Shivang Joshi, MD, MPH, RPh, a trial investigator and neurologist at Dent Neurologic Institute, in Amherst, New York, said in a statement, “Lilly’s CHALLENGE-MIG study will help us understand how different types of preventive medications may help people achieve the goals that matter most to them. 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.”2
Secondary end points of the trial include greater than 75% and 100% reduction from baseline in monthly migraine headache 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.
Safety, specifically adverse events, will also be recorded in the phase 4 study. To date, the adverse effects reported in clinical studies of galcanezumab include site reactions, such as injection site pain, erythema, and pruritus, as well as hypersensitivity reactions following the administration of the drug. For rimegepant, patients in clinical trials have reported nausea and some rare cases of hypersensitivity reactions. Patients on this drug have also experienced severe hypersensitivity reactions with symptoms such as dyspnea and rash.1
As the toolbox of FDA-approved medications has expanded in recent years, the emphasis on treatment optimization and conducting these types of comparative studies has gained more traction. In May 2021, a study conducted by Popoff et al made matching-adjusted indirect comparisons using rimegepant subject-level data and published aggregate-level results from mAb trials. 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