麻豆传媒

Another biologic for migraine has passed a late-stage prevention test: in patients with chronic migraine, fremanezumab significantly reduced the number of headache days when taken monthly or quarterly compared with placebo, researchers reported.

From a baseline of about 13 headache days per month, quarterly subcutaneous dosing offered a 4.3-day reduction, and monthly dosing offered a 4.6-day reduction -- both significantly greater than the 2.5-day reduction seen with placebo (P<0.001 for both), Stephen Silberstein, MD, of the Jefferson Headache Center in Philadelphia, and colleagues

Fremanezumab is the latest calcitonin gene-related peptide (CGRP) blocker to report late-stage data. Final data on Amgen's erenumab (Aimovig) from the STRIVE trial in patients with episodic migraine were , but did not change substantially from when they were reported at the 2017 American Academy of Neurology meeting. Also, Eli Lilly reported data on galcanezumab earlier this year, as .

All four are human monoclonal antibodies; erenumab targets the CGRP receptor, while the other three target the peptide itself.

In the fremanezumab study, researchers randomized chronic migraine patients to one of three groups: a quarterly injection of 675 mg at baseline followed by placebo injections at weeks 4 and 8; a monthly injection of 675 mg at baseline followed by 225 mg at weeks 4 and 8; or a matching placebo injection.

Overall, there were 376 patients in the quarterly group, 379 in the monthly group, and 375 in the placebo group. The mean headache days per month at baseline was about 13 in all groups.

The primary endpoint was mean change from baseline in the average number of headache days per month, defined as days in which headache pain lasted at least 4 consecutive hours and had a peak severity of at least a moderate level, or days in which acute migraine-specific medications such as triptans were used to treat a headache of any severity.

In addition to finding greater mean reductions in average monthly headache days with both drug groups over placebo, they also found that a greater proportion of drug-treated patients had a reduction of at least 50% in monthly headache days (38% for quarterly dosing, 41% for monthly dosing, and 18% for placebo, P<0.001).

Injection-site reaction occurred in 47% of each of the quarterly and monthly dosing groups compared with 40% of the placebo group, and injection site pain occurred in 30% of those on the quarterly dose, 26% of those on the monthly dose, and 28% of those on placebo.

Mild transient elevations in liver enzyme levels occurred in some patients, but levels reverted to normal without stopping the trial regimen, the researchers reported. All patients who had these elevations used concomitant medications that have the potential to cause increases in liver enzymes, they noted.

Fremanezumab drugmaker Teva is also doing a parallel trial of the CGRP inhibitor in episodic migraine.

In an accompanying editorial, Andrew Hershey, MD, PhD, of Cincinnati Children's Hospital, noted that with four drugs targeting the CGRP pathway, "it will be difficult to determine whether unique patient populations will have a response to a specific drug or whether one agent is superior to others."

"Furthermore, many patients will probably still have a response to standard multidisciplinary treatment that is less costly in patient and provider time and dollars," Hershey noted. "It is of interest that these agents worked rapidly and that a number of patients became completely headache-free. Thus, these drugs may find a specific role in the treatment of patients who have migraines that are refractory to treatment or who are severely disabled by headaches."

In the long run, he added, it ill be "important to determine whether the beneficial effect can be sustained after discontinuation or whether continued treatment will be necessary."

Hershey concluded that a migraine-specific preventive treatment that is "directed toward a suspected underlying patho-physiological mechanism is an important advance for patients with migraine."