Objective:

To investigate the pharmacokinetics (PK) and safety of Lu AG09222 using data from three phase 1 clinical trials. 

Background:

Lu AG09222 is a humanised monoclonal antibody targeting pituitary adenylate cyclase-activating polypeptide (PACAP) that is in development for migraine prevention.

Design/Methods:

Data were included from a (1) first-in-human single ascending dose trial in healthy participants, including a cohort with co-administered sumatriptan (Lu AG09222 n=68; placebo n=28); (2) single-dose trial in healthy Caucasian, Chinese, and Japanese participants (Lu AG09222 n=40; placebo n=12); and (3) multiple-dose trial in participants with symptomatic allergic rhinitis (Lu AG09222 n=20; placebo n=10). Assessments included intravenous (IV) doses ranging from 1 mg to 750 mg and subcutaneous (SC) doses of 100 mg and 600 mg.

Results:

Overall, 128 and 50 participants received Lu AG09222 and placebo, respectively. Half-life was ~15 days (IV) and ~15–17 days (SC). Bioavailability after SC administration was ~80%. Maximum serum concentration and area under the curve increased in a dose-proportionate manner in participants receiving single IV doses from 1 mg to 750 mg. After multiple SC doses, exposure increased proportionally between 100 mg and 600 mg. There were no PK differences by sex, and PK was comparable in Caucasian, Japanese, and Chinese cohorts. Co-administration with sumatriptan did not result in PK interactions. Most treatment emergent adverse events (TEAEs) were mild; the most common TEAEs were injection site reactions (SC) and headache (both IV and SC). One serious AE, perniosis of moderate severity, occurred in a participant 112 days after receiving a single IV dose of 750 mg Lu AG09222 co-administered with sumatriptan. 

Conclusions:

Lu AG09222 exhibited a consistent PK profile across dosing regimens, route of administration and race/ethnicity. Across these trials, no safety concerns were identified, and Lu AG09222 was generally well-tolerated.