It’s been six years since Otsuka got its Lundbeck-partnered antipsychotic Rexulti approved to treat schizophrenia in the US. Now, the company has its sights set on a new approach for the difficult-to-treat disease — and it’s putting down close to $1 billion to snag that candidate and three others from fellow Japanese drugmaker Sumitomo Dainippon Pharma.
Otsuka is shelling out $270 million upfront and another $620 million in biobucks for joint development and commercialization rights to four neuropsychiatric compounds from Sumitomo Dainippon’s subsidiary Sunovion, the companies said on Thursday.
Ulotaront (SEP-363856), a schizophrenia treatment that entered Phase III back in 2019, is the furthest along. The company’s bipolar depression candidate SEP-4199 isn’t far behind, having entered a Phase III trial earlier this month. Meanwhile, SEP-378614 and SEP-380135, discovered in collaboration with PsychoGenics, are still in Phase I.
Last April, Sunovion
uncorked
some positive Phase II results for ulotaront, showing an average 17.2-point improvement on the Positive and Negative Syndrome Scale used to assess schizophrenia, compared to a 9.7-point improvement for the placebo group.
Schizophrenia is assessed according to both “positive” symptoms, such as movement issues and abnormal thoughts or perceptions, and “negative” ones, such as the loss of motivation or pleasure. While researchers still have much to learn about the disease, they traced part of those effects to excess dopamine. Current drugs that block the dopamine receptor D2 help mitigate the positive symptoms but have had less success treating the negative ones. Rexulti, on the other hand, is a D2 receptor partial agonist.
Ulotaront is designed to act on two dopamine-affecting receptors, called TAAR1 and 5-HT1A, while leaving D2 alone. While Phase II study’s secondary endpoints weren’t powered to be statistically significant, researchers reported seeing promising results on the negative symptoms.
Next in line is SEP-4199, which produced some
mixed results
in bipolar I depression last summer. A Phase II trial enrolled 344 patients who were experiencing major depressive episodes associated with bipolar I disorder. But at the topline readout, the study failed to meet its primary endpoint: a significant improvement on the Montgomery-Åsberg Depression Rating Scale after six weeks of treatment.
CSO Kenneth Koblan blamed the results on a high placebo response, adding: “Despite the high placebo response in this study, which is known to diminish the effect size and the ability to detect a signal, the topline results suggest that SEP-4199 has the potential to be an effective advance in treatment for people with bipolar depression.”
SEP-378614 and SEP-380135 are in Phase I trials for treatment-resistant depression and agitation in Alzheimer’s disease, respectively.
According to the terms of their new deal, Sunovion and Otsuka will share profits from the four compounds, as well as all expenses for clinical studies, regulatory filings, and commercialization.
“Otsuka has been committed to providing new antipsychotics that contribute to patients worldwide in the field of neuropsychiatry by leveraging internal capabilities and external collaborations, starting with the launch of antipsychotics in the U.S. in 2002,” Makoto Inoue, president and representative director of Otsuka, said in a statement.
“Through this agreement, we are confident the companies will be able to deliver even more value to patients through the experience and networks that we have cultivated over many years worldwide,” he added.
