A prespecified futility analysis of a phase 3 study revealed that the primary endpoint of mean change from baseline in the weekly average number of cluster headache attacks during the 4-week treatment period is unlikely to be met.
Tushar Shah, MD
Teva Pharmaceuticals has announced the discontinuation of its clinical development program of fremanezumab for the treatment of episodic cluster headache after a prespecified futility analysis of a phase 3 study revealed that the primary endpoint of mean change from baseline in the weekly average number of cluster headache attacks during the 4-week treatment period is unlikely to be met.
Teva previously discontinued its clinical trial program for fremanezumab in chronic cluster headache in June 2018, after a futility analysis demonstrated that there would likely be no beneficial treatment effect within the 12-week treatment period. Fremanezumab (Ajovy, Teva) was previously approved by the FDA in September 2018 for the prevention of migraine, and is also currently being investigated in post-traumatic headache.
“We’d like to thank the patients and investigators for their immense contributions to this study,” Tushar Shah, MD, senior vice president, head of Global Specialty Clinical Development, Teva, said in a statement.1 “Despite these results, we are continuing to evaluate if fremanezumab treatment can provide clinical benefits in additional diseases where anti-calcitonin gene-related peptide therapy may play a role in its pathophysiology.”
The now discontinued ENFORCE clinical trial program included phase 3 studies in chronic cluster headache, episodic cluster headache, and a long-term safety study for the prevention of cluster headache.
The migraine treatment landscape continues to be increasingly competitive as several anti-CGRP therapies look to make their mark. While fremanezumab is now established as a safe and effective therapy for migraine prevention, alongside erenumab and galcenezumab, which is also being investigated in cluster headache, but there remains no FDA-approved pharmaceutical therapies for cluster headache. Previously, the FDA granted clearance to electroCore's gammaCore vagus nerve stimulation device for the treatment of acute pain associated with cluster headache, and recently expanded its indication as an adjunctive treatment for the prevention of cluster headache.
"It is difficult to develop new products in the headache world for diseases that are rare like cluster headache, which is an orphan disease," stated Stephen Silberstein, director, Jefferson Headache Center at Jefferson University Hospital. "In contrast to episodic and chronic migraine, monoclonal antibodies do not appear to be effective in chronic or episodic cluster headache, leading to this discontinuation. While oxygen therapy has been shown to be effective for cluster headache, Medicare refuses to pay for it, so we must continue to explore other treatment options for this population."
Teva Announces Update on Fremanezumab Clinical Development for use in Episodic Cluster Headache [news release]. Jerusalem: Teva Pharmaceutical Industries; April 23, 2019. https://seekingalpha.com/pr/17484469-teva-announces-update-fremanezumab-clinical-development-use-episodic-cluster-headache. Accessed April 23, 2019.