Preclinical and clinical evaluation of LY3451838, a PACAP-neutralizing monoclonal antibody, in randomized, double-blind, placebo-controlled phase 1 and phase 2 studies involving healthy adults and adults with treatment-resistant migraine
Abstract
Aim LY3451838 is a monoclonal antibody against pituitary adenylate cyclase-activating peptide (PACAP), a target in migraine research. The present study aimed to evaluate LY3451838 as a preventive treatment for participants with treatment-resistant migraine. Methods Following preclinical assessment of LY3451838, including pharmacokinetic and pharmacodynamic studies, safety was evaluated in a phase 1 study of LY3451838 (n = 33) versus placebo (n = 13) in healthy participants. A phase 2 trial was carried out in treatment-resistant participants with chronic migraine (CM) (n = 16) or episodic migraine (EM) (n = 22). In phase 2, participants received a single intravenous (IV) dose of 1500 mg LY3451838 (n = 19) or placebo (n = 19) and completed ePRO daily diaries. Participants were followed for safety for 140 days. Results In phase 2, at one-month post-dose, patients who had received a single IV dose of LY3451838 exhibited greater changes from baseline than placebo in mean monthly migraine headache days in both the CM and EM subgroups (CM: −4.7 days vs. −3.0 days; EM: −1.7 days vs. −1.2 days), but the treatment contrast was not statistically significant in either subgroup. Similar non-significant results were seen at the three-month time point. The percentage of participants reporting treatment-emergent adverse events was similar for LY3451838 and placebo, with one serious adverse event of B-cell lymphoma in an LY3451838-treated participant that led to study discontinuation.…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 33 participants or records.
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