Lilly's migraine drug gets key cluster headache approval

The FDA has approved Eli Lilly’s Emgality (galcanezumab-gnlm) for the treatment of episodic cluster headache in adults, giving the calcitonin gene-related peptide (CGRP) antibody a key point of differentiation over rivals from Teva and Amgen.

There are no preventative treatments with high-quality evidence backing their efficacy in cluster headache, according to the American Headache Society. Analysts have suggested an effective drug for this indication could reach blockbuster-level sales if approved.

Emgality (galcanezumab-gnlm) was approved by the FDA last September for migraine prevention, shortly after Amgen’s Aimovig (erenumab) and Teva’s Ajovy (fremanezumab) received the go-ahead from the US regulator.

But now Lilly’s drug has become the first to add cluster headaches to its label, following a breakthrough designation awarded last November.

Teva’s Ajovy failed a phase 3 trial in cluster headache prevention last year, curbing the Israeli drugmaker’s aspirations to extend the indications for its CGRP inhibitor beyond migraine.

Meanwhile, Amgen doesn’t seem to be testing Aimovig in cluster headache, with no trials in that indication listed on clinicaltrials.gov or their respective pipeline tables.

Emgality’s application was based on data from a phase 3 GCAL study in adults with cluster headache which showed that between weeks 1 and 3 of the two-month treatment period, subjects taking Emgality experienced 8.7 fewer cluster headache days compared to 5.2 fewer days for placebo.

That only just cleared the bar for significance with a p value of 0.036, so Lilly also relied on secondary endpoints to build a positive clinical picture for its drug. For instance, three-quarters (71.4%) of those on Emgality had at least a 50% reduction in weekly cluster headache attacks compared to 52.6% for the placebo at week 3, the study’s secondary endpoint.

To put those results in perspective, subjects in the trial averaged more than 17 cluster headache attacks per week during the baseline period, equivalent to 2-3 every day.

Cluster is far less common than migraine, but is often characterised as being severely debilitating with recurrent, intense headaches that occur in cyclical patterns on one side of the head, frequently associated with pain behind or around one eye, as well as restlessness and agitation.

According to Lilly, cluster headache attacks typically last between 15 to 180 minutes, occurring near daily to multiple times daily during a cluster period, and can be “severely disabling and excruciatingly painful.”

After training by a healthcare professional, patients can administer Emgality at home through subcutaneous injections at the onset of a cluster headache period, and then monthly until the end of a cluster period.