Cannabinoid receptor 2 agonist, lenabasum, for the treatment of pulmonary exacerbations in cystic fibrosis.

BACKGROUND

Lenabasum is a cannabinoid receptor 2 (CB2) agonist under development for cystic fibrosis (CF), targeting inflammation. We evaluated the efficacy and safety of lenabasum in people with CF (pwCF).

METHODS

We conducted a global, 28-week, randomized, double-blind, placebo-controlled Phase 2b trial. PwCF were ≥12 years old with 2-3 pulmonary exacerbations (PEx) treated with intravenous (IV) antibiotics (or 1 PEx treated with IV and ≥1 PEx treated with oral antibiotics) in the past year. Subjects were randomized 2:1:2 to lenabasum 20 mg BID, lenabasum 5 mg BID, or placebo BID. Primary endpoint was rate of PEx, comparing lenabasum 20 mg BID to placebo.

RESULTS

Among 447 subjects from 21 countries, mean age was 26.9 (10.3 SD) years, 53.6% were female, 45.2% homozygous for F508del, and 24.9% received CFTR modulators. Highest ppFEV1 in the previous year was 69.2% with the majority having 1-2 PEx treated with IV antibiotics (2-7 PEx treated with either IV or oral antibiotics). PEx incidence over 28 weeks was 0.84 for placebo, 0.75 for lenabasum 5 mg BID, and 0.91 for lenabasum 20 mg BID; rates were not lower relative to placebo in the 5 mg (incidence rate ratio (IRR)=0.89, 95% CI 0.66 to 1.19, p = 0.44) or the 20 mg group (IRR 1.08, 95% CI 0.86 to 1.37, p = 0.51). PEx occurred less frequently in participants from Eastern Europe, but there was no evidence of regional variation in treatment efficacy. Lenabasum was well tolerated, without safety signals.

CONCLUSION

Lenabasum did not improve key clinical outcomes in this Phase 2b study in pwCF.