Although there were no concerns regarding the safety profile of the CGRP inhibitor, the reduction in cluster headache attacks from baseline over the 12-week treatment period was underwhelming.
Tushar Shah, MD
Teva Pharmaceuticals is altering its plans for the clinical development of fremanezumab for the treatment of chronic cluster headache, announcing that the primary endpoint of the ENFORCE phase 3 program will not be met, and thus that portion of the trial, as well as the long-term safety examination, will be discontinued.
The ENFORCE program sought to enroll 600 patients in total, with plans to last 68 weeks. Although there were no concerns regarding adverse events or the safety profile of the calcitonin gene-related peptide (CGRP) inhibitor in the chronic cluster headache trial, the reduction in cluster headache attacks from baseline over the 12-week treatment period was underwhelming.
“While we are disappointed with this outcome, we remain optimistic that fremanezumab could have clinical benefits in additional conditions, beyond migraine, where [CGRP] plays a contributory role in their pathophysiology,” said Tushar Shah, MD, the senior vice president and head of Global Specialty Clinical Development at Teva, in a statement. “We would like to thank the patients and investigators for their participation in the Chronic Cluster Clinical Trial.”
The other study in the ENFORCE program, of the therapy’s impact on episodic cluster headache, will continue as planned, according to Teva. That trial will seek to enroll 300 patients, randomizing them to 2 treatment arms and a placebo arm. Its primary outcome is the mean change from baseline in the weekly average number of cluster headache attacks during a 4-week period after first administration of fremanezumab.
Despite this setback, the CGRP inhibitor may still have a future as a migraine therapy. In November 2017, the results of a study exploring the therapy in chronic migraine showed a least squares mean (±SE) reduction in the average headache days experienced per month by 4.3 ±0.3 for a 675-mg dose given quarterly, while a 225-mg dose administered monthly revealed a reduction of 4.6 ±0.3 headache days (P <.0001).
Comparatively, the trial’s placebo group experienced a 2.5 ±0.3 reduction in headache days— almost half of that of quarterly and monthly groups.
Currently, fremanezumab is under review by the U.S. Food and Drug Administration (FDA), with a prescription drug fee user act (PDUFA) date of September 16, 2018, and by the European Medicines Agency (EMA), seeking an indication as an injection—either quarterly or monthly—for the preventive treatment of migraine in adults.
Teva’s Biologics License Application (BLA) for the therapy was accepted by the FDA in May. At the time, Hafrun Fridriksdottir, the executive vice president of Global R&D at Teva said that the company’s primary goal was “to bring preventive treatment options to migraine patients as quickly as possible.”
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