Eli Lilly Launches Phase 4 Head-to-Head Trial Comparing Emgality and Nurtec ODT in Episodic Migraine Prevention

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Last month, Biohaven's oral medication Nurtec ODT received U.S. FDA approval for a second indication: the preventive treatment of migraine, specifically for adult patients with episodic migraine (EM) who experience fewer than 15 headache days per month. Previously, in February 2020, Nurtec ODT had already been approved by the FDA for the acute treatment of migraine (with or without aura) in adults, regardless of the number of monthly migraine days.

With this latest approval, Nurtec ODT is the first oral CGRP antagonist approved for the preventive treatment of migraine, and the only migraine medication approved for both acute and preventive treatment.

Eli Lilly now aims to directly compare its antibody-based migraine therapy, Emgality, with Nurtec ODT. On Tuesday, the company announced that it will conduct a head-to-head study to advance the science of migraine treatment and help elucidate the roles of CGRP monoclonal antibodies (mAbs) versus oral CGRP receptor antagonists in migraine prevention. The trial will directly compare Emgality (a once-monthly subcutaneous injection) with Nurtec ODT (an orally disintegrating tablet taken every other day).

Reportedly, this study is the first head-to-head clinical trial comparing two CGRP-targeted drugs. It is a multicenter, randomized, double-blind, double-dummy, parallel-group Phase IV study enrolling patients with episodic migraine (EM) with or without aura who meet the International Classification of Headache Disorders (ICHD) criteria. The study will comprise two treatment arms: (1) Emgality 120 mg administered subcutaneously once monthly, with a starting dose of 240 mg; and (2) Nurtec ODT 75 mg taken every other day. The primary endpoint is the proportion of patients achieving a 50% reduction in monthly migraine days. Patient enrollment is expected to begin later this year.

Calcitonin gene-related peptide (CGRP) is a protein in the brain that is believed to play a key role in migraine. Emgality is a monoclonal antibody that specifically binds to CGRP, preventing it from binding to its receptor, while Nurtec ODT is an oral CGRP receptor antagonist that directly blocks the CGRP receptor. According to an announcement by Eli Lilly, this newly initiated Phase 4 clinical trial aims to address several critical questions to help clinicians and patients make more informed treatment decisions on the path toward more migraine-free days.

To date, Nurtec ODT is the first and only medication indicated for both the preventive and acute treatment of migraine. Meanwhile, Emgality is the first and only CGRP antibody indicated for two distinct headache disorders. In addition to its use in the preventive treatment of migraine, it is also approved for the treatment of episodic cluster headache (ECH), a condition characterized by excruciatingly painful headache attacks that typically occur at the same time each day and persist for weeks to months.

In response to Eli Lilly's initiation of a head-to-head study, Vlad Coric, CEO of Biohaven, stated on Tuesday: "Nurtec ODT has 'clearly established' its position as the industry-leading CGRP therapy, and the company is highly confident in its advantages. Currently, treatment sentiment among migraine patients is shifting toward oral CGRP-targeted drugs. In our view, this study by Eli Lilly is a competitive move by a company with injectable therapies to maintain market share."

In late May, when Nurtec ODT was approved for a second indication, Vlad Coric touted the drug's convenience in an interview with Fierce Pharma, stating that physicians would no longer need to prescribe separate migraine treatment regimens for patients; simply prescribing Nurtec ODT would suffice, as it can be used for both migraine prevention and acute treatment.

Nevertheless, Vlad Coric also pointed out that monoclonal antibodies are a better option for patients with high-frequency migraine attacks. Eli Lilly, however, believes that the results of this head-to-head study will provide significant value for migraine treatment decision-making.

In the migraine market, both Eli Lilly and Biohaven face competition from other rivals. Currently, the FDA is reviewing AbbVie’s oral CGRP receptor antagonist atogepant for migraine prevention. Previously, AbbVie’s other oral CGRP receptor antagonist, Ubrelvy (ubrogepant), was approved by the FDA in late 2019 for the acute treatment of migraine. Meanwhile, several other CGRP-targeting monoclonal antibody migraine therapies are available on the market, including Aimovig (Amgen/Novartis), Ajovy (Teva), and Vyepti (Lundbeck), all of which are indicated for preventive treatment.

Source: Eli Lilly pins injectable migraine med Emgality against Biohaven's oral rival Nurtec ODT in head-to-head study