On Friday, February 27, 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) announced on its website that it recommends rejecting the marketing authorization application for Emgality® (galcanezumab) for the prophylaxis of episodic cluster headache in adults. The amendment sought to expand the indication to include the prevention of attacks in adults with episodic cluster headache. For this use, Emgality was to be made available as a 100 mg pre-filled syringe.
Emgality is a medicine for the prevention of migraine in adults who experience migraine on at least four days per month. It has been authorized in the EU since November 2018. It contains the active ingredient galcanezumab and can be administered subcutaneously using a 120 mg pre-filled syringe.
The company applied for an extension of the indication to prevent attacks of episodic cluster headache. Cluster headaches cause very severe pain, typically on one side of the head around one eye. Attacks last up to 3 hours and can occur several times a day during active cluster periods, which can last for weeks to months.
CGRP is involved in the development of the headaches. It dilates, sensitizes, and inflames blood vessels in the brain. The active ingredient in Emgality, galcanezumab, is a monoclonal antibody designed to bind to and block CGRP, causing the blood vessels to return to their normal diameter. This stops the headaches.
In a pivotal trial involving 106 patients with episodic cluster headaches, Emgality was compared to placebo (a dummy treatment). The primary efficacy endpoint was a reduction in the frequency of headache attacks per week over a three-week period. The results of the study in patients with episodic cluster headaches did not definitively demonstrate that Emgality is effective in preventing attacks. The agency therefore concluded that the benefits of Emgality in preventing attacks in patients with episodic cluster headaches did not outweigh the risks. Consequently, the agency recommended rejecting the amendment to the marketing authorization. There are no consequences for the use of Emgality for migraine prevention in adults.
Based on the CHMP's negative recommendation, the manufacturer, Eli Lilly, announced that galcanezumab will not receive marketing authorization in the EU for the prophylaxis of episodic cluster headaches. Lilly deeply regrets this decision, particularly since cluster headaches are an extremely painful and debilitating condition, and very few treatment options are approved or permitted for use in Germany according to Section IV of the Drug Directive.