Roche Terminates Second Phase II Schizophrenia Trial

Pictured: Blue Roche logo on white building/Smith Collection/Gado/Getty Images

Pictured: Blue Roche logo on white building/Smith Collection/Gado/Getty Images

Roche has terminated a second Phase II trial of its investigational schizophrenia drug ralmitaront, leaving an uncertain future for the company’s program targeting the psychiatric disorder.  

The first trial, which was canceled last year, was studying the effects of ralmitaront as a monotherapy in patients with an acute exacerbation of positive symptoms of schizophrenia or schizoaffective disorder. The second trial, which was recently terminated, was investigating the impact of the treatment on negative symptoms associated with the two conditions.

“In a preliminary analysis, the primary endpoint was negative, and ongoing portions of the study have therefore been discontinued,” according to an update on the second Phase II trial posted to the website.

Roche’s latest first quarter 2023 pipeline presentation included the asset, pushing its New Molecular Entity submission back into the “2026 and beyond” category. No other trials for the drug are listed on the federal clinical trials or Roche websites.

The cancelation of Roche's second mid-stage trial for ralmitaront comes as the competition shows promise.

Ralmitaront is an agonist of the trace amine-associated receptor 1 (TAAR1). Sunovion Pharmaceuticals’ ulotaront is an investigational agonist of TAAR1 and serotonin 5HT1A in Phase III studies for schizophrenia. The treatment has proven to be effective at treating both the positive psychosis symptoms and the elusive negative symptoms of schizophrenia. Negative symptoms affect patients’ ability to function normally and include lack of motivation and emotion and difficulty socializing. There is currently no FDA-approved treatment for these symptoms.

Otsuka Pharmaceutical forged a nearly $1 billion deal in 2021 with Sunovion’s parent company, Sumitomo Pharma, which includes ulotaront. The treatment received Breakthrough Therapy Designation from the FDA for schizophrenia. Topline results are expected from the Phase III study in 2023.

The industry is also closely watching Karuna Therapeutics’ KarXT. It too appears to be effective in treating both the positive and negative symptoms of schizophrenia, although it has not been specifically tested for negative symptoms.

An NDA is anticipated for the investigational M1/M4-preferring muscarinic agonist by the middle of this year. If approved, KarXT will be the first new class of drug for schizophrenia in over 50 years.

Also hoping to score a “first,” Acadia Pharmaceuticals’ pimavanserin is being studied in a Phase II trial specifically for the negative symptoms of schizophrenia. The treatment could be added to the existing regimens of antipsychotics which work to control the positive symptoms.

BioSpace reached out to Roche for comment on the future of ralmitaront and its schizophrenia program, but the company was not immediately available.

Kate Goodwin is a freelance life science writer based in Des Moines, Iowa. She can be reached at and on LinkedIn.  

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