Sumitomo Pharma and Otsuka Face Challenges as Ulotaront’s Potential as a Schizophrenia Treatment Remains Uncertain
Date: July 30, 2023
Sumitomo Pharma and Otsuka’s ambitious plan to transform ulotaront into a blockbuster growth driver has encountered setbacks. Two phase 3 clinical trials investigating ulotaront as a treatment for schizophrenia failed to meet their primary endpoints, leaving the partners to examine a “high placebo response” as they consider the candidate’s future in addressing the disease.
In 2021, Otsuka made a significant investment, paying $270 million upfront for rights to a portfolio of candidates, with ulotaront as the lead asset. The AAR1 agonist with 5-HT1A agonist activity was already in phase 3 trials for schizophrenia treatment. For Sumitomo, ulotaront represented a potential blockbuster that could offset declining sales of its antipsychotic drug, Latuda. The partners also had plans to explore ulotaront’s potential in depression and anxiety disorders.
Phase 3 Trials and Results:
The two phase 3 trials enrolled a total of 899 acutely psychotic adults with schizophrenia. Participants were randomized to receive one of two doses of ulotaront or a placebo, and the primary endpoint was the measurement of symptom changes after six weeks.
Unfortunately, none of the ulotaront doses demonstrated superiority over the placebo. In the DIAMOND 1 trial, both daily doses (50 mg and 75 mg) showed reductions in scores on a schizophrenia symptom severity scale, but the placebo group also exhibited similar reductions, making the differences statistically insignificant. Similar results were observed in the DIAMOND 2 trial, where doses of 75 mg and 100 mg showed numerically larger mean reductions compared to placebo, but the differences did not reach statistical significance.
High Placebo Response and COVID-19 Impact:
Sumitomo CEO, Hiroshi Nomura, expressed his belief that a “high placebo response” may have obscured the potential therapeutic effect of ulotaront. Notably, the placebo response in the DIAMOND 1 trial was particularly pronounced. The partners suspect that the COVID-19 pandemic may have influenced the placebo responses seen in the studies, as the trials were conducted during the pandemic.
Addressing the Challenges:
High placebo response rates are common challenges in psychiatric clinical trials, and Sumitomo and Otsuka believe that the pandemic may have exacerbated this issue. Before the pandemic, ulotaront demonstrated promising efficacy trends in a pooled analysis of data from the two DIAMOND trials, similar to what was seen in the phase 2 study.
Next Steps and FDA Consultation:
Sumitomo and Otsuka are currently analyzing the data thoroughly and are planning to engage in discussions with the FDA to determine the appropriate next steps. Both companies have significant stakes in the success of ulotaront, with Otsuka considering it a next-generation growth driver, and Sumitomo projecting potential sales across all indications that could rival its fading blockbuster, Latuda.
The journey to establish ulotaront as a breakthrough schizophrenia treatment has faced challenges with the recent phase 3 trial outcomes. The partners remain determined to unravel the complexities of the high placebo response and evaluate the potential impact of the pandemic on the results. As the companies work towards resolving these issues, the future of ulotaront’s role in treating schizophrenia remains uncertain.
For more information on the ongoing developments and future plans for ulotaront, please refer to Sumitomo Pharma and Otsuka‘s official press releases and updates.

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