Dr Gudarz DavarGudarz Davar, MD
Eli Lilly and Company has announced that galcanezumab (Emgality) has met all primary and key secondary end points in the phase 3 CONQUER study in the preventive treatment of chronic and episodic migraine.1

The primary objective was to demonstrate the superiority of the anti-calcitonin gene-related peptide (CGRP) agent versus placebo in the number of monthly migraine headache days across months 1 through 3. The overall galcanezumab cohort experienced a 4.1-day reduction in monthly migraine headache days compared to a 1.0-day reduction with placebo (P <.0001).

"Preventive treatment failure has been a common occurrence among patients with migraine," said Gudarz Davar, MD, vice president, neurology development, Lilly Bio-Medicines, in a statement. "The CONQUER study applied strict and rigorous criteria to identify and enroll patients with chronic and episodic migraine who had failed multiple migraine preventive treatments, with the goal of understanding whether Emgality may be an effective option for patients with such significant unmet need."

The study was designed and conducted based on a subgroup analysis of prior galcanezumab studies. As such, all 462 patients in the trial had documented failures on ≥2–4 prior standard-of-care preventive migraine medications due to safety and tolerability. In total, 41.7% (n = 193) and 58.2% (n = 269) of patients had chronic and episodic migraine, respectively.

Treatment failure was defined as inadequate efficacy post ≥2 months of treatment at a maximum tolerated dose or discontinuation of use due to safety or tolerability issues. Failure to respond to preventive migraine medicines is common in this patient population, with international estimates placing more than 40% of patients who use migraine preventive medications as having a history of failure or switching treatments.

All key secondary end points—50%, 75%, and 100% responder rates; and improvements in the Migraine-Specific Quality of Life Questionnaire Role Function-Restrictive (MSQ-RFR) domain—were met with statistical significance from the galcanezumab group. Eli Lilly announced that the details of those outcomes will be presented at an upcoming scientific congress and published in a peer-reviewed journal.

As for safety, the CONQUER trial's observed safety profile was consistent with previous findings.

Galcanezumab is a monoclonal antibody approved by the FDA in September 2018 for the preventive treatment of migraine in adults, and then in June 2019 for the treatment of episodic cluster headache in adults.

In July 2019, data published from a group of trials evaluating a dose of 300 mg in patients with cluster headache suggested that the drug can reduce weekly attacks in those with episodic disease, but not in those with chronic cluster headache. Compared to placebo, the monoclonal antibody against CGRP reduced weekly attacks by 3.5, on average. All told, the 49-patient episodic cohort randomized to galcanezumab experienced a mean reduction of 8.7 cluster headache attacks across weeks 1 to 3, compared to 5.2 in the 57-patient placebo group (95% CI, 0.2–6.7; P =.04).2

In the study of chronic disease, it achieved neither its primary end point nor its key secondary end points. The clinical differences between the treatment groups were not significantly different, though the safety profile of galcanezumab was found to be consistent with previous trials.3
REFERENCES
1. Lilly Announces Positive Results for Emgality® (galcanezumab-gnlm) from the CONQUER Study in Patients who Failed Previous Migraine Preventive Treatments [press release]. Indianapolis, IN; Eli Lilly & Co.; Published August 5, 2019. prnewswire.com/news-releases/lilly-announces-positive-results-for-emgality-galcanezumab-gnlm-from-the-conquer-study-in-patients-who-failed-previous-migraine-preventive-treatments-300895947.html. Accessed August 5, 2019.
2. Goadsby PJ, Dodick DW, Leone M, et al. Trial of galcanezumab in prevention of episodic cluster headache. N Engl J Med. 2019;381:132-141. doi: 10.1056/NEJMoa1813440.
3. Dodick DW. Phase 3 placebo-controlled study of galcanezumab in patients with chronic cluster headache: results from 3-monht double-blind treatment. Presented at: American Headache Society annual meeting. July 11-14, 2019; Philadelphia, PA.