Brilaroxazine Shows Long-Term Efficacy in Schizophrenia in Phase 3 RECOVER

Reviva Pharmaceuticals announced positive topline data from the Phase 3 RECOVER study’s open-label extension, showing brilaroxazine's once-daily efficacy for schizophrenia was sustained beyond 1 year.

The study also showed long-term safety for brilaroxazine at all 3 doses (15 mg, 30 mg, and 50 mg) with >5% having no single adverse event. The discontinuation rate was 35%.

Brilaroxazine has potent affinity and selectivity against key serotonin and dopamine receptors that are involved in the pathophysiology of several conditions such as schizophrenia, psoriasis, pulmonary hypertension, pulmonary arterial hypertension, and idiopathic pulmonary fibrosis. The efficacy and safety were already seen in phase 3 RECOVER, a 4-week placebo-controlled trial, and showed promise in improving symptoms for schizophrenia.

“No current therapy addresses all needs of patients with schizophrenia,” said Scott Bartley, MD, chief medical officer and principal investigator for Pillar Clinical Research and investigator in the RECOVER trials “The broad-spectrum improvements in all major symptom domains, including negative symptoms, along with the low treatment discontinuation rates with long-term use of brilaroxazine are encouraging and support the potential of brilaroxazine to reduce the current burden on people affected by this debilitating and life-long mental illness.”

To evaluate the long-term safety and efficacy of brilaroxazine for schizophrenia, investigators conducted an open-label extension portion of RECOVER, enrolling 435 patients, 139 of whom were on brilaroxazine 15 mg, 155 on 30 mg, and 141 on 50 mg. 35.86% of participants came from the double-blind portion of the phase 3 trial, and 64.13% were new to the research.

The preliminary efficacy results include data from 113 patients who completed 52 weeks, or 1 year, of treatment. The safety results include data from 435 patients, including participants still in the ongoing trial.

The open-label extension demonstrated dose-dependent efficacy with decreases in the PANSS total scores (from baseline to 52 weeks) of -15.2, -18.6, and -20.8 points for participants on doses 15, 30, and 50 mg, respectively. Pooled data showed clinically meaningful and sustained 1-year efficacy for schizophrenia with a significant reduction in PANSS total scores (-18.6 points; P ≤ .0001), PANSS positive symptoms (-5.2 points; P ≤ .0001), and PANSS negative symptoms (-4.5 points; P ≤ .0001) from baseline.

Additionally, participants originally from the double-blind portion of the trial showed sustained efficacy from the acute phase, with reductions of 30 points, 40 points, and 50 points, in the PANSS total score for 86.76%, 64.80%, and 33.82% participants, respectively.

Moreover, the trial found brilaroxazine to be well-tolerable. 15.2% of participants reported ≥ 1 treatment-related adverse event, although most were mild (12.2%) or moderate (3%) in severity. The most common treatment-related adverse events were weight increase (3.2%), insomnia (1.8%), and somnolence (1.6%). Brilaroxazine was not linked to any clinically meaningful changes in movement disorder scales after 1 year of treatment.

The team found no serious adverse events related to brilaroxazine treatment. The 3 reported serious adverse events were unrelated to the treatment.

The discontinuation rate of 35% was primarily attributed to the withdrawal of consent (22%), loss to follow-up (7%), and treatment-related adverse events (1.6%).

Ultimately, the open-label extension further supported the safety, efficacy, and treatment adherence of brilaroxazine for schizophrenia from the 4-week double-blind portion. RECOVER is still ongoing, conducted globally in several centers to assess the safety and efficacy of the drug at doses of 15, 30, and 50 mg once daily for 52 weeks.

“We believe these topline preliminary long-term data build on the strong clinical evidence demonstrating that brilaroxazine can improve all major symptom domains of schizophrenia, and now importantly, show sustained efficacy over time,” said Laxminarayan Bhat, Ph.D., Founder, President, and CEO of Reviva. “We look forward to reporting the full data set from the OLE portion of the RECOVER study, which will include long-term safety, tolerability, and efficacy data, as well as vocal and blood biomarker data as additional independent measures of efficacy, expected in the first quarter of 2025.”

References

Reviva Announces Positive Preliminary Topline Data for the Long-Term Open Label Extension Portion of the Phase 3 RECOVER Study Evaluating Brilaroxazine in Schizophrenia. Global Newswire. December 16, 2024. https://www.globenewswire.com/news-release/2024/12/16/2997485/0/en/Reviva-Announces-Positive-Preliminary-Topline-Data-for-the-Long-Term-Open-Label-Extension-Portion-of-the-Phase-3-RECOVER-Study-Evaluating-Brilaroxazine-in-Schizophrenia.html. Accessed December 16, 2024.