Lilly claims fast FDA review for Emgality in cluster headache


Eli Lilly has a battle on its hands in the migraine prevention category with third-to-market CGRP inhibitor Emgality but could get a leg-up with an indication in episodic cluster headache.

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.

Lilly’s drug could be the first to add cluster headache to its label however, with the FDA starting a speedy priority review of the drug having awarded it a breakthrough designation in cluster headache last November.

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.”

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’s marketing application is 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 is also relying on secondary endpoints to build a positive clinical picture for its drug. For instance, three-quarters (76%) of those on Emgality had at least a 50% reduction in weekly cluster headache attacks compared to 57% 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.

The positive result was nevertheless encouraging for Lilly given the lack of current treatment options, and particularly as Teva’s fremanezumab 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 and partner don’t seem to be testing erenumab in cluster headache, with no trials in that indication listed on or their respective pipeline tables.

“The pain associated with cluster headache can be agonizing and crippling, with deep searing, burning, and stabbing pain, leaving people feeling desperate for new preventive treatment options,” says Bob Wold, a person living with cluster headache and the founder of charity Clusterbusters.

“On behalf of the patient community, we are grateful to Lilly for their commitment to researching and working with regulatory authorities to potentially deliver a preventive treatment option for those living with episodic cluster headache, he adds.