Teva’s Migraine Candidate Shows Promising Late-Stage Data

A medication to prevent migraine—whether injected either monthly or quarterly—was found to produce a significant reduction in headache days for patients with chronic (CM) and episodic migraine (EM).

Teva Pharmaceuticals reported positive topline results from Phase III trials of fremanezumab, an investigational treatment for the prevention of migraine, at the International Headache Conference (IHC) earlier this month.

In Phase III HALO studies in CM and EM, the monoclonal antibody fremanezumab met all 25 pre-specified study endpoints across both monthly and quarterly dosing regimens.

“When we studied fremanezumab in patients with less than 14 headaches per month or more than 14 headaches per month, in those 25 comparisons we did, we showed statistically significant results in favor of fremanezumab when compared to placebo, ” said Ernesto Aycardi, M.D., Vice President & Therapeutic Area Head, R&D Migraine and Headache at Teva Pharmaceuticals in an interview with Drug Discovery & Development.

“But more important to understand is that these comparisons were regardless of whether you have quarterly dosing or monthly dosing,” he stressed. “That is really significant for patients.”

The HALO trials

Fremanezumab was tested in a 16-week, multi-center, randomized, double-blind, placebo-controlled and parallel group study. The EM arm had 875 patients assigned to either placebo, quarterly, and monthly regimens, while the CM arm had 1,130 patients randomized to either placebo, monthly and quarterly regimens.

Migraine groups receiving fremanezumab saw more than a 50 percent reduction in monthly average number of migraine days of least moderate severity for both dosing regimens compared to placebo.

For CM, those randomized to fremanezumab for monthly dosing saw a reduction of 4.6 days, and those for quarterly dosing saw a reduction of 4.3 days compared to a 2.5-day reduction in those with placebo.

In the EM study, monthly migraine days were reduced by 3.7 days for the monthly regimen group and 3.4 days for the quarterly regimen group, compared to a 2.2-day reduction in those with placebo.

Other endpoints met included improvements in quality-of-life and health measures, less work productivity loss and significant reductions in impairment activity outside of work.

The most commonly-reported adverse event in the EM and CM trials was pain at the injection site, with similar rates in the placebo and active groups.

The mechanism of fremanezumab

Self-administered via injection, fremanezumab works by targeting the calcitonin gene-related peptide (CGRP) ligand, a well validated target in migraine. This is a new class of treatment, said Aycardi, as there is no drug approved with this mechanism of action.

The current treatment for prevention of migraine consists of medications that were developed for other conditions, not for migraine. For example, Aycardi cited that people are using medications that are indicated for seizure, blood pressure, depression or even for cosmetic reasons (think Botox). “All of those medications were just found to also work in migraine, and that’s why people use them,” he explained.

“This medication is specifically designed for migraine. The CGRP protein has proved to be critical in the pathology of migraine,” explained Aycardi. “What we did was develop an antibody that tackles and goes only to CGRP. It’s very specific, it doesn’t bind to any other proteins in the body. It just goes in and binds and blocks that protein, and by blocking that protein it prevents the occurrence of new migraine attacks.”

Convenience of dosing

“It’s just not a headache problem that we’re solving,” said Aycardi. “We are improving headaches but also other things that will make patients’ lives a lot easier. And it’s going to help these patients become a lot more productive in life.”

The flexibility and convenience of choosing either monthly or quarterly dosing is a unique advantage. In addition, the medication has a very good risk-to-benefit profile. “It not only improves the headache, it improves the other symptoms that patients may have with migraine, like nausea, vomiting, photophobia, phonophobia, and at the same time reducing the levels of disability,” explained Aycardi. “I think the social benefits this is going to have is really significant.”

This is a very promising time for patients with migraines and for doctors, added Aycardi. “I think that, after 20 years of not having anything new it’s significant for the prevention of migraine. This is going to help thousands, no millions, of patients worldwide.”

With more than 40 million people in U.S. alone suffering from migraine, it’s not an overstatement, but we’ll have to wait until the drug receives approval to find out.

Teva is in the process of finalizing applications to the FDA and expect to file in the coming months.