Johnson & Johnson’s depression drug JNJ-5120 fails primary endpoint in phase 2 trial

A phase 2 study of JNJ-5120, an M1 receptor antagonist developed by Johnson & Johnson with Contineum Therapeutics, did not meet its primary efficacy endpoint in patients with major depressive disorder.

The trial enrolled 107 participants who were randomly assigned to receive one of two doses of JNJ-5120 or placebo. At the Day 5 assessment, scores on the depression rating scale were indistinguishable between the drug and placebo groups, leading to the missed endpoint.

The setback follows a previous failure of a separate phase 2 trial of the same compound in relapsing‑remitting multiple sclerosis. Analysts at William Blair removed JNJ-5120 from their valuation models, cutting the previously estimated 35% chance of success.

The outcome highlights the challenge of demonstrating efficacy in placebo‑controlled depression studies, where high placebo response rates can dilute treatment effects.