A vaccine as a potentially safe and effective immunotherapy against CGRP

UB-313 may become an affordable and convenient new option to prevent migraine. Designed to stimulate the production of endogenous antibodies against calcitonin gene-related peptide (CGRP), the vaccine UB-313 has now advanced to clinical development. The ongoing first-in-human study of UB-313 will assess the safety, tolerability, and immunogenicity of 4 selected UB-313 dose regimens in healthy adults.

The UB-313 vaccine is projected to be less expensive than the currently available CGRP inhibitors, making it a more accessible treatment option for migraineurs. The longer-lasting effectiveness would also make it more convenient to use.

Dr Jean-Cosme Dodart (Vaxxinity Inc, FL, USA) presented the ongoing phase 1 trial on UB-313 (NCT05477095) assessing safety, immunogenicity and target engagement: capsaicin-induced increase in dermal blood flow [1]. It is a single-site, randomised, double-blind, placebo-controlled, multidose regimen study of UB-313 performed at the University Hospital in Leuven, Belgium. The study duration is 44 weeks, consisting of intramuscular injections of UB-313 or placebo at week 0 (baseline, day 1), week 4 and week 12, and follow-up. Participants are healthy men and women aged 18 to 55 years without migraine.

Immunogenicity studies of UB-313 were already conducted in animal models (rodents and monkeys). UB-313 was found to induce robust anti-CGRP antibodies across species. Affinity-purified antibodies bound human CGRP with high affinity, resulting in a (dose-dependent) functional inhibition of CGRP. The properties of antibodies from immunised animals were comparable with CGRP antibodies currently on the market. The specificity of the anti-CGRP antibodies for human CGRP was very high and UB-313-induced antibodies had a stronger effect on human CGRP than on rat CGRP, despite a single amino acid substitution between species.

Preclinical toxicology studies indicated UB-313 to be safe and well-tolerated. Adverse events were limited to injection site reactions and UB-313 seems to safely overcome immune tolerance.

1. Dodart J-C. UB-313, an investigational CGRP vaccine for the prevention of migraine. ES1.005, AAN 2023 Annual Meeting, 22–27 April, Boston, USA.

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Posted on 26 June 20231 February 2024