New Study Published in Cephalalgia Identifies Mechanistic Differences Among CGRP Migraine Treatments

Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) highlights results from the in vitro study “Migraine Therapeutics Differentially Modulate the CGRP Pathway,” which were published online by Cephalalgia, a monthly journal published on behalf of the International Headache Society. These results will also be featured in a future print issue of the journal. This study demonstrated marked differences in the mechanism of blocking the calcitonin gene-related peptide (CGRP) ligand versus the CGRP receptor.

This newly-published study evaluates three distinct mechanistic classes of drugs based on receptor binding, signaling and drug internalization: (1) Monoclonal antibodies against the CGRP ligand, (2) The monoclonal antibody against the CGRP receptor and (3) ‘Gepants’, small molecule inhibitors of the CGRP receptor.

“This in vitro study explored these mechanistic differences by comparing the tested compounds in the same experimental analyses, and found that the different ways to target the CGRP pathway may have a different biologic impact,” said Steffen Nock, Senior Vice President of Global Biologics, Teva. “For instance, fremanezumab in particular, as a monoclonal antibody against the CGRP ligand, is targeted and specific in its mechanism.”

AJOVY (fremanezumab-vfrm) injection is a fully humanized IgG2ΔA monoclonal antibody that specifically and solely targets CGRP, a key neuropeptide involved in the pathophysiology of migraine. Since 2018, multiple CGRP pathway-based therapeutics have been approved by the U.S. Food and Drug Administration (FDA). These in vitro study data indicate that CGRP receptor targeting therapeutics bind at multiple receptors and prevent the subsequent signaling of several peptides, while AJOVY selectively binds to only CGRP, suggesting that its mechanism is specific while other receptor targeting treatments have potential for an off-target binding.

Importantly, this in vitro research found that an agent that targets the CGRP receptor versus the ligand, also bind to the human amylin AMY₁ receptor, affecting signaling and undergoing internalization at both receptors suggesting a potential difference in their biologic function.

Clinical implications of these findings are unknown, but the in vitro studies provide insights into potential mechanistic differences. This study was supported by Teva, and all authors are full-time Teva employees.

AJOVY is the first and only long-acting anti-CGRP subcutaneous injection approved in the U.S. and EU for the preventive treatment of migraine in adults that offers both quarterly and monthly dosing options.^1+±