Eli Lilly has recently initiated the enrollment of a Phase IV preventive migraine trial for its anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb), Emgality (galcanezumab), compared to Biohaven’s Nurtec (rimegepant) in adult participants with episodic migraine. The initiation of the Challenge-MIG trial (NCT05127486) reflects the increased competition among migraine prophylaxis products and Eli Lilly’s efforts to solidify its position in an increasingly crowded market.

In the past, head-to-head studies for migraine prophylaxis focused on comparing anti-CGRP mAbs with the traditional oral preventive therapies such as antidepressants, anti-epileptic agents, and beta blockers. In particular, Amgen and Novartis committed significant resources towards conducting head-to-head trials comparing its Aimovig (erenumab) with traditional oral preventives for migraine prevention. For example, results from the head-to-head HER-MES trial (NCT03828539) showed that Aimovig had a superior tolerability and efficacy profile compared with the anti-epileptic, topiramate. The study found that a greater proportion of patients achieved at least 50% reduction in their monthly migraine days with Aimovig and this treatment arm had less discontinuation over the course of the 24-week treatment phase, compared to topiramate. The findings of the company’s second head-to-head study with the traditional oral prophylactic drugs (NCT03927144) have not yet been announced.

However, competition has grown fiercer since the launch of gepants like Biohaven’s Nurtec and AbbVie’s Qulipta (atogepant) for migraine prophylaxis in episodic migraine patients. Eli Lilly’s trial is the first head-to-head study comparing an oral gepant with a subcutaneously administered mAb, both of which target the same migraine signaling pathway. The Challenge-MIG study is expected to enroll 700 adults across the US. Primary outcome measures will evaluate the proportion of patients with at least 50% reduction in monthly migraine days across a three-month double-blind period. In addition, the proportion of patients with a 75% and 100% reduction in monthly migraines will also be analyzed, a secondary outcome measure that has been uncommon in previous migraine prevention studies.

Key opinion leaders interviewed by GlobalData noted that the convenient administration of oral gepants is often favored by primary care physicians and general practitioners. However, Nurtec’s every-other-day dosing schedule could impair compliance in patients, as it may be difficult for patients to track medication days and breaks. This risk is lower with Emgality which has a longer duration of action and is administered monthly. While Nurtec can be used for acute migraine treatment, it has not yet been investigated whether Emgality is effective at aborting migraine attacks. With the growing availability of migraine prophylactic products, post-marketing head-to-head clinical trials will be key to differentiate products from one another.

Emgality and the other anti-CGRP mAbs will face even more gepant competition in the near future. AbbVie’s Qulipta received FDA approval in September 2021 for preventive treatment of episodic migraine and is being studied in ongoing trials for the prevention of chronic migraine (NCT03855137). Furthermore, Biohaven is investigating its pipeline agent, oral zavegepant, for preventive migraine treatment. GlobalData forecasts that zavegepant will be launched in the US in Q3 2024.

Eli Lilly is a strong player in the migraine market with acute and preventive products, Reyvow (lasmiditan) and Emgality, respectively. Biohaven is also a strong contender with a portfolio of small molecule CGRP antagonists. As such, success in the Challenge-MIG head-to-head trial is critical to ensuring the companies’ futures in the field.