Brilaroxazine improves symptoms with safety among patients with schizophrenia: Phase 3 Recover trial

USA: A Phase 3 RECOVER trial evaluating the efficacy, safety and tolerability of once-daily brilaroxazine, a serotonin-dopamine signalling modulator in adults with schizophrenia has yielded positive toplines results and is successfully completed, as announced by the pharmaceutical company Reviva. 

The trial successfully met its primary endpoint, with brilaroxazine at the 50 mg dose achieving a statistically significant and clinically meaningful 10.1-point reduction in Positive and Negative Syndrome Scale (PANSS) total score compared to placebo (-23.9 brilaroxazine 50 mg vs. -13.8 placebo, p<0.001) at week 4. Brilaroxazine achieved statistically significant and clinically meaningful reductions in all major symptom domains and secondary endpoints at week 4 with the 50 mg dose vs. placebo. The 15 mg dose of brilaroxazine was numerically superior to placebo on the primary and most secondary endpoints and reached statistical significance on two key secondary endpoints.

“We are excited to report positive topline results for our Phase 3 RECOVER trial, further confirming the well-tolerated safety profile and improvements in all major symptom domains including PANSS total score, positive and negative symptoms, and Clinical Global Impression – Severity score (CGI-S) as previously observed in our Phase 2 REFRESH trial,” said Laxminarayan Bhat, Ph.D., Founder, President, and CEO of Reviva. “Importantly, we believe the unique multifaceted mechanism of action of brilaroxazine, a serotonin-dopamine signalling modulator, has the potential to improve additional key disease drivers like neuroinflammation.

The RECOVER pivotal results highlight the potentially differentiated therapeutic profile of once-daily brilaroxazine and underscore the potential to address treatment limitations for the 24 million people living with schizophrenia around the world. We expect to report long-term data from our OLE trial in the fourth quarter of 2024 and initiate a registrational Phase 3 RECOVER-2 trial in the first quarter of 2024, which if successful will help support our planned New Drug Application (NDA) submission to the FDA expected in 2025.”

Key statistically significant and clinically meaningful improvements with brilaroxazine vs. placebo in patients with schizophrenia and a mean PANSS total score of 97-99 at baseline include:

Larry Ereshefsky, PharmD, BCPP, FCCP, Chief Scientific Officer, Follow the Molecule: CNS Consulting and Clinical Sciences by CenExel Research added, “The consistent response across all primary and secondary endpoints at the 50 mg dose and improvement in all major domains, including, negative symptoms and personal and social performance is strong support for brilaroxazine’s robust activity. Moreover, the low placebo response is indicative of a well-run trial employing quality sites and investigators. This broad efficacy profile coupled with low discontinuation rates and favorable tolerability supports the potential of brilaroxazine to address limitations of standards of care and potentially be a long-term treatment option for this chronic and complex disease.”

Key clinical safety and tolerability findings of brilaroxazine support a well-tolerated safety profile:

No drug related serious adverse events (SAEs) or treatment-emergent SAEs (TESAEs) observed or major safety concerns reported for brilaroxazine after 4 weeks of treatment

No incidence of suicidal ideation

No significant change in body weight, blood glucose levels, lipids levels, or endocrine hormones (prolactin, thyroid hormone) compared to placebo

Akathisia and extrapyramidal symptoms <1% reported for brilaroxazine 50 mg and none for 15 mg

Low discontinuation rates with brilaroxazine that were less than placebo (16% in brilaroxazine 50mg and 19% in brilaroxazine 15mg vs. 22% placebo)

The brilaroxazine program consists of the completed positive Phase 2 REFRESH and Phase 3 RECOVER trials, as well as an ongoing 1-year OLE trial evaluating the long-term safety and tolerability, and soon to be initiated confirmatory global, randomized 6-week Phase 3 RECOVER-2 trial. The Company expects to report topline data from the OLE trial in Q4 2024 and initiate the registrational Phase 3 RECOVER-2 trial in Q1 2024, with completion anticipated in early 2025. These data from the brilaroxazine program will potentially support the planned NDA submission to the FDA in 2025.