Following the news that Sumitomo and Otsuka’s ulotaront failed to meet the primary endpoints in the Phase III DIAMOND 1 and DIAMOND 2 trials, treating acutely psychotic adults with schizophrenia;

Christie Wong, Neurology Analyst at GlobalData, a leading data and analytics company, offers her view:

“As all members of the atypical antipsychotic drug class have the same mechanism of action (MOA), and therefore a similar efficacy profile, differentiated only by slight nuances in their safety profiles, patients who do not respond to atypical antipsychotics have limited options to manage their schizophrenia symptoms. Key opinion leaders (KOLs) previously interviewed by GlobalData hoped that a product with a novel MOA would unlock the first new drug class for schizophrenia in over 60 years and potentially improve responses in treatment resistant patients.

“Prior to ulotaront’s topline results from DIAMOND 1 and DIAMOND 2, KOLs were enthusiastic about the drug’s first-in-class MOA.  Ulotaront is an oral once-daily tablet that is an agonist of 5-HT receptor 1A and trace amine-associated 1 (TAAR-1) receptors. Prior to news regarding negative topline data for ulotaront, GlobalData had expected the drug to launch in the US and Japan in Q4 2024 and Q2 2027, respectively, and generate $644.2 million in sales by 2031.

“These data sets are quite a blow to the developers, particularly Sumitomo. The sales of ulotaront could have helped Sumitomo compensate for anticipated declining sales associated with the patent expiry of its atypical antipsychotic, Latuda (lurasidone hydrochloride), starting in 2026. Even with this setback, Otsuka will remain a strong player in the schizophrenia market, having received FDA approval for Abilify Asimtufii (injectable aripiprazole dosed once every two months) for the treatment of schizophrenia in April 2023. In addition, Otsuka has a once-weekly formulation of brexpiprazole in Phase III development for schizophrenia (NCT05325645).

“If the companies decide to move forward with ulotaront, it is likely that additional efficacy data for the drug will be required by the FDA, further delaying the drug’s launch behind other potential competitors. Most notably, Karuna Therapeutics’s KarXT (xanomeline + trospium chloride), a potential first-in-class product developed to target the positive and negative symptoms of schizophrenia by activating central muscarinic receptors. The safety and efficacy of KarXT is supported by data from the Phase III EMERGENT program. GlobalData forecasts that KarXT will launch in the US in Q3 2024 and accrue sales of $1.1 billion by 2031.”