Disappointing Results for Ulotaront in 2 Phase 3 Schizophrenia Trials

Ulotaront was not found to significantly benefit patients with schizophrenia more than placebo in 2 phase 3 studies, according to Sumitomo Pharma and Otsuka Pharmaceutical.

The DIAMOND 1 (ClinicalTrials.gov Identifier: NCT04072354) and DIAMOND 2 (ClinicalTrials.gov Identifier: NCT04092686) studies evaluated the safety, efficacy and tolerability of ulotaront, a trace amine-associated receptor 1 (TAAR1) agonist with 5-HT_1A agonist activity, vs placebo in acutely psychotic adults with schizophrenia. The primary endpoint for both studies was the change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score at week 6.

In DIAMOND 1, patients (N=435) were randomly assigned to receive ulotaront 50 mg/day, 75 mg/day, or placebo. Results showed neither ulotaront group was superior to placebo; change from baseline in PANSS total score at week 6 (least squares [LS] mean) was reported to be -16.9 and -19.6 with ulotaront 50 mg and 75 mg, respectively, and -19.3 with placebo.

In DIAMOND 2, patients (N=464) were randomly assigned to receive ulotaront 75 mg/day, 100 mg/day, or placebo. Neither treatment group demonstrated a statistically significant improvement compared with placebo; change from baseline in PANSS total score at week 6 (LS mean) was reported to be -16.4 and -18.1 with ulotaront 75 mg and 100 mg, respectively, and -14.3 with placebo.

According to the companies, a large placebo effect was observed in both studies, which may have masked the therapeutic effects of ulotaront. “High placebo responses, like those seen in DIAMOND 1 and DIAMOND 2, are well documented in psychiatric clinical studies,” explained Hiroshi Nomura, representative director, president and CEO of Sumitomo Pharma. “The placebo response in DIAMOND 1 was particularly high. These studies were conducted throughout the COVID-19 pandemic and initial analyses of these data suggest an impact of COVID-19 on the placebo responses that were seen. We continue to work closely with Otsuka and analyze the data to determine our next steps and plan to discuss with the US FDA how to proceed based on these results.”

In 2019, ulotaront was granted Breakthrough Therapy designation by the FDA for the treatment of schizophrenia. The TAAR1 agonist is also being evaluated as a treatment for generalized anxiety disorder (ClinicalTrials.gov Identifier: NCT05729373) and as an adjunctive therapy for major depressive disorder (ClinicalTrials.gov Identifier: NCT05593029).

This article originally appeared on MPR