Lilly drug scrapes through cluster headache trial

A sad young woman is sitting in her kitchen with a headache

Eli Lilly’s galcanezumab works, but not that well, in devastatingly painful cluster headaches according to results of a phase 3 trial.

The announcement comes the day before the FDA is due to announce whether or not it will approve Novartis and Amgen’s erenumab, another drug in a gang of four calcitonin gene-related peptide (CGRP) drugs approaching the market for migraine.

Analysts have suggested the drugs could reach blockbuster-level sales if approved in a disease for which there are limited available treatment options.

Phase 3 results of the late-stage trial of galcanezumab in patients with episodic cluster headache, showed statistically significant differences in reduction of weekly cluster headaches compared with placebo across weeks one to three of the two-month double-blind treatment period.

A statistically significantly greater percentage of patients treated with monthly galcanezumab also achieved at least a 50% reduction in weekly cluster headache attacks compared with placebo at week 3, a gated secondary endpoint.

But digging into the numbers presented by Lilly shows that although patients in the galcanezumab arm had 8.7 fewer headaches in the first three weeks of treatment, those in the placebo arm experienced 5.2 fewer headaches.

This marked improvement in the placebo group produced a “p” value of 0.036 – uncomfortably close to the 0.05 threshold that would have produced a result deemed to be a failure.

In the study 8% of patients discontinued treatment with galcanezumab, compared with 21% of patients with placebo.

In the galcanezumab arm 4% of patients stopped treatment because of adverse events, compared with 2% of patients on placebo.

Discontinuations due to lack of efficacy occurred in 2% of patients treated with galcanezumab, compared to 14% of patients treated with placebo.

Lilly said it is working with regulators to decide the best path forward with galcanezumab, a self-injected drug, in cluster headaches.

The FDA is already reviewing data from three phase 3 trials testing galcanezumab in migraine, where the drug produced statistically significant reductions in monthly migraine headache days compared with placebo at both studied doses.

The FDA is due to make a decision on galcanezumab in migraine in Q3. It is due to make a decision on Teva's fremanezumab by next month, and biotech Alder is to file its eptinezumab infusion later this year.