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Galcanezumab Gets FDA Go-Ahead for Migraine Prevention

This approval marks the third of its kind in the calcitonin gene-related peptide inhibitor class, starting with erenumab in May 2018.

David Dodick, MD

The FDA has green-lit galcanezumab-glnm (Emgality) 120 mg for the preventive treatment of migraine in adults, according to manufacturer Eli Lilly & Co.1

The calcitonin gene-related peptide (CGRP) inhibitor’s approval marks the third of its kind, following erenumab (Aimovig, Amgen/Novartis) in May 2018, and fremanezumab (Ajovy, Teva) earlier this month. Its list price is $575 once-monthly, or $6,900 annually, according to Eli Lilly.

The supporting data for the biologics license application was supplied from the EVOLVE-1, EVOLVE-2, and REGAIN clinical trials, which evaluated the efficacy and safety of subcutaneous injections of galcanezumab at 120 mg or 240 mg once-monthly, following a 240-mg starting dose. In the trials, which evaluated the therapy in 2,901 patients, those treated with the monoclonal antibody experienced a statistically greater decrease in the average number of monthly migraine days compared with the placebo.

“Glass half-empty people might look and say, ‘Well, the efficacy of the responder rates don’t look that much different than what we see with other treatments we’ve been using for years,’ and that’s true,” David Dodick, MD, a neurologist at Mayo Clinic who’s been involved with multiple trials of headache medicines, including galcanezumab, told NeurologyLive. “On the other hand, we know that at least with the oral treatments in use for migraine prevention, the tolerability is not very good. Studies have been published showing that over 80% of people who are started on an oral preventive drug for migraine prevention are no longer taking that drug after 1 year. And these are patients who have chronic migraine and have a very large unmet treatment need, who are the most disabled.”

“If the most disabled patients in this group—8 out of every 10—can’t tolerate or don’t respond to these drugs and are not on them after 1 year, that’s a problem,” Dodick added. He said that the difference with the CGRP inhibitors is the fact that they have, by and large, placebo-like tolerability. Patients have been able to adhere to the medication long-term.

In EVOLVE-12, a significant percentage of patients treated with both doses achieved a reduction of ≥50%, ≥75% and 100% in the number of migraine days compared with placebo throughout the treatment period. In total, 62.3% of those on the 120-mg dose and 60.9% for the 240-mg dose achieved ≥50% reduction, versus 38.6% for placebo (P <.001).

Meanwhile, a ≥75% reduction was achieved by 38.8% of those in the 120-mg dose group and 38.5% in the 240-mg dose group, compared to 19.3% for placebo (P <.001); and 15.6% of the 120-mg dose group and 14.6% of the 240-mg dose group experienced a 100% reduction versus 6.2% for placebo (P <.001).

In EVOLVE-23, a significant percentage of patients also treated with both doses achieved at least a 50%, 75% and 100% reduction in the number of migraine headache days compared to placebo throughout the treatment period. Patients that experienced a ≥50% reduction were as follows: 59.3% for the 120-mg dose, 56.5% for the 240-mg dose, and 36% for placebo. Likewise, those that experienced a ≥75% reduction was 33.5%, 34.3%, and 17.8% for the 120-mg, 240-mg, and placebo groups, respectively. In total, 11.5% of the 120-mg group and 13.8% of the 240-mg group achieved a 100% reduction, versus 5.7% for placebo.

Additionally, patients treated with galcanezumab in both of the EVOLVE studies experienced a greater reduction of monthly migraine headaches with acute medication use compared to those treated with placebo.

Throughout a 3-month treatment period, patients with chronic migraine in the REGAIN study4 treated with galcanezumab 120-mg and 240-mg doses experienced a statistically greater decrease in the average number of monthly migraine headache days versus placebo. A greater percentage of patients also achieved a ≥50% reduction in the number of migraine headache days versus placebo throughout the treatment period (27.6% for the 120-mg dose and 27.5% for the 240-mg dose versus 15.4% for placebo).

Compared with placebo, patients treated with the 240-mg dose of galcanezumab achieved a ≥75% reduction in the number of migraine headache days (8.8% versus 4.5% for placebo) after multiplicity adjustment and achieved a greater reduction in the number of monthly migraine headache days with acute medication use (an average of 4.3 days compared to 2.2 days for placebo).

Galcanezumab was further evaluated in REGAIN for an additional 9 months of an open-label extension phase following the 3-month phase.

“The longer [patients] stay on [the CGRPs], if you look at the 1-year, open-label data for those that are staying on it, efficacy rates climb over time,” Dodick said. “So, while in 2 months, let’s say, you may have a reduction by 50%. At 6 months, you may be at 75%, and at 12 months you might have had an 80% or 90% reduction. The longer you’re able to adhere to a treatment that’s working for you, the better the patient outcome is over time. That’s the real difference here.”

“The fact that for those who GGRP appears to be a very important mechanism, we may see these super-responders. We may see these people for whom there’s just been a dramatic change in the expression of this disease because of the pivotal role that CGRP plays in the biology of their illness,” he added.

In a June presentation at the American Headache Society’s 60th Annual Meeting in San Francisco, California, the therapy reported efficacy in a cluster headache trial. Patients were treated with either 300-mg galcanezumab once monthly or placebo, with assessments across weeks 1 to 3. The trial therapy revealed a -8.7 reduction in weekly cluster headaches compared to -5.2 with placebo (P = .036). Of those receiving galcanezumab, 76% achieved a ≥50% reduction in weekly cluster headache attacks at week 3, compared to 57% with placebo (P = .04).



Lilly's Emgality™ (galcanezumab-


) Receives U.S. FDA Approval for the Preventive Treatment of


in Adults [press release]. Indianapolis



Eli Lilly & Co;

Published September 27, 2018.

https://markets.businessinsider.com/news/stocks/lilly-s-emgality-galcanezumab-gnlm-receives-u-s-fda-approval-for-the-preventive-treatment-of-migraine-in-adults-1027572874. Accessed September 27, 2018.

2. Stauffer VL, Dodick DW, Zhang Q, et al. Evaluation of galcanezumab for the prevention of episodic migraine: the EVOLVE-1 randomized clinical trial. JAMA Neurol. 2018;75(9):1080-1088. doi:10.1001/jamaneurol.2018.1212.

3. Skljarevski V, Matharu M, Millen BA, Ossipov MH, Kim BK, Yang JY. Efficacy and safety of galcanezumab for the prevention of episodic migraine: Results of the EVOLVE-2 Phase 3 randomized controlled clinical trial. Cephalagia. 2018 Jul;38(8):1442-1454. doi: 10.1177/0333102418779543.

4. AHS 2018: Lilly’s Emgality (galcanezumab-gnlm) Significantly Reduced Monthly Migraine Headache Days in Patients with Migraine Who Previously Failed Botox (onabotulinumtoxinA) [news release]. Indianapolis, IN: Eli Lilly & Co; Published June 27, 2018. investor.lilly.com/news-releases/news-release-details/ahs-2018-lillys-emgalitytm-galcanezumab-gnlm-significantly. Accessed September 27, 2018.