FDA approves galcanezumab-gnlm—a humanized mAb—for episodic migraine

Naveed Saleh, MD, MS, for MDLinx | October 26, 2018

The US Food and Drug Administration (FDA) recently approved galcanezumab-gnlm for the prevention of episodic migraines in adults. This 120-mg subcutaneous injection is administered by the patient once a month, following a one-time initial loading dose of 240 mg or two consecutive 120-mg doses.

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Once-monthly treatment with galcanezumab-gnlm brought about significant reductions in monthly migraine headache days, and migraine-related functional impairment and disability.

Great need exists for novel treatments for migraine that are safe and well tolerated. One recent study indicated that 54% of patients with migraine required bed rest or experienced severe impairment. Additionally, although 39% of patients with migraine could benefit from preventive medications, only 13% receive such medications. Moreover, up to 68% of those who take such preventive medications discontinue them within 6 months due to poor tolerability or lack of benefit.

Galcanezumab-gnlm is a humanized monoclonal antibody (mAb) that binds calcitonin gene-related peptide (CGRP)—a protein in the brain and nervous system involved with pain transmission—and interferes with its biological activity without blocking its receptor. Levels of CGRP in the blood rise during migraine attacks, and CGRP infusion results in headache in migraine patients.

The FDA approval is based on safety and efficacy results demonstrated in two phase 3 clinical trials in adult patients with episodic migraine (EVOLVE-1 and EVOLVE-2), as well as a phase 3 clinical trial in patients with chronic migraine (REGAIN). In all trials, baseline migraine headache days (MHDs) per month in patients receiving the drug and placebo hovered at around 9 days.

After an initial loading dose of 240 mg, researchers administered either 120 or 240 mg galcanezumab-gnlm each month of the study. Of note, in a previous phase 2 trial, monthly doses of 120 mg and 300 mg both exhibited clinical efficacy.

Both EVOLVE-1 and EVOLVE-2 were double-blind, placebo-controlled studies that lasted 6 months, with episodic migraine defined by the researchers as 4-14 MHDs per month.  

In the EVOLVE-1 trial, patients treated with galcanezumab-gnlm (120 mg) experienced a mean baseline reduction in monthly MHDs of 4.7 days vs 2.8 days with placebo (P < 0.001). Furthermore, 62% of treated patients (n=210) experienced a 50% or greater decrease in MHDs per month vs 39% of those taking placebo (n=425; P < 0.001).

In the EVOLVE-2 trial, patients taking galcanezumab-gnlm (120 mg) experienced an average drop in monthly MHDs of 4.3 days vs 2.3 with placebo (P < 0.001). Additionally, 59% of treated patients (n=226) achieved a ≥ 50% decrease in MHDs per month vs 36% of those taking placebo (n=450; P < 0.001).

In the REGAIN trial—a 3-month, double-blind, placebo-controlled study—patients taking galcanezumab-gnlm (120 mg) experienced a mean reduction in monthly MHDs of 4.8 days vs 2.7 days in those taking placebo (P < 0.001). Additionally, 28% of treated patients (n=273) experienced a ≥ 50% drop in MHDs per month vs 15% of those taking placebo (n=538; P < 0.001).

Investigators evaluated drug safety in all three trials in more than 2,500 patients. Overall, the drug was well tolerated. The most common adverse event was injection site reactions and erythema.

“[Galcanezumab-gnlm] treatment was associated with a statistically significant and clinically meaningful reduction in monthly MHDs at doses of 120 and 240 mg given subcutaneously once monthly,” concluded the EVOLVE-2 investigators, led by Vladimir Skljarevski, MD, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN, in a study published in Cephalalgia. “Moreover, patients treated with either dose of [galcanezumab-gnlm] reported a reduction in the migraine-related impairment of function and a significant reduction in migraine-related disability, while also reducing the use of acute migraine medications.”

The EVOLVE 1 and 2 studies were sponsored by Eli Lilly and Company. The REGAIN trial received funding from Alexion Pharmaceuticals.

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