CGRP and Gepant Combination Safe, DNL788 Fails ALS Study, Frexalimab Promising Phase 2 Results in Relapsing MS

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Welcome to this special edition of Neurology News Network. I’m Marco Meglio.

A recently published retrospective study found that a combination of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mABs) with gepants was a safe and well-tolerated treatment approach for patients with migraine. To the authors knowledge, this was the largest, real-world descriptive study that reported on the adverse events (AEs) experienced by patients who were prescribed CGRP antagonists and gepants concurrently. Out of the 234 patients on combined therapy, 3 (1.2%) patients reported AEs, which included peri-labial numbness and cough, nausea and vomiting, and constipation (each 1). None of these reported AEs led to discontinuation of combined treatment.

According to an SEC filing report from Denali therapeutics, the company’s investigational agent DNL788 failed to meet its primary end point of change on ALS Functional Rating Scale-Revised (ALSFRS-R) in the phase 2 HIMALAYA trial (NCT05237284) of patients with amyotrophic lateral sclerosis (ALS). The company plans to present the detailed efficacy and safety results of the study at a future scientific forum.The 2-part study used change in ALSFRS-R total score at week 24, as well as the combined assessment of the function and survival (CAFS) score at week 52, as the coprimary outcome measures.

In a phase 2 study of patients with relapsing multiple sclerosis (MS) published in the New England Journal of Medicine, the use of frexalimab (Sanofi), a CD40L inhibitor, resulted in favorable reductions in the number of gadolinium-enhancing T1-weighted lesions relative to placebo. The company has already begun to initiate phase 3 studies assessing the agent in relapsing MS and non-relapsing secondary progressive MS. The double-blind, placebo-controlled trial randomly assigned patients to either 1200 mg of frexalimab administered intravenously every 4 weeks (with an 1800-mg loading dose), 300 mg of frexalimab administered subcutaneously every 2 weeks (with a 600-mg loading dose), or matching placebos. Of the 129 participants included, 125 (97%) completed the 12-week double-blind period and entered the open-label period.

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