Safety, Tolerability, and Adherence
In the preliminary Open-Label Extension (OLE) study for brilaroxazine, 15.2% of participants reported at least one treatment-related adverse event (TRAE), with the majority being mild (12.2%) or moderate (3%). The most common TRAEs included weight increase (3.2%), insomnia (1.8%), and somnolence (1.6%). Importantly, no drug-related serious adverse events (SAEs) were reported, and there were no observations of movement disorders, such as tardive dyskinesia or acute dystonia, which are often associated with first and second-generation antipsychotics.
Discontinuation rates were notably favorable, reaching 35% at the one-year mark. This is significantly lower compared to other approved antipsychotics, which typically see discontinuation rates ranging from the mid-40% to 70%. For instance, Bristol Myers’ recently approved KarXT had a discontinuation rate of 53% after 52 weeks of treatment.
RECOVER-2 Phase III Trial
Reviva Pharmaceuticals is preparing to launch its confirmatory Phase III RECOVER-2 trial in the first quarter of 2025. This trial will build on the foundation laid by the initial RECOVER trial, with some key differences. The study will randomize 450 patients in a 1:1:1 ratio to receive either 30 mg, 50 mg, or a placebo, with endpoints measured over a 4-week period.
To facilitate the trial, Reviva entered into a start-up agreement with an additional contract research organization on January 9, 2024, paying $1.1 million to initiate activities. The company has also reached an agreement with the FDA regarding the content required for a new drug application (NDA). The FDA has stipulated the need for two positive Phase III studies demonstrating efficacy at week four, accompanied by safety data spanning at least 12 months. Additionally, a long-term randomized withdrawal study will be required post-approval to support the maintenance of effect.
Capital Raise
Following the positive preliminary OLE data, Reviva Pharmaceuticals executed a capital raise to fund the RECOVER-2 trial and support operations until approval. On December 16, 2023, the company announced the pricing of its offering, raising $18 million gross. The offering consisted of 12 million units, each comprising one share of common equity, 0.5 series A warrant, and one series B warrant. The warrants have exercise prices of $1.50, with six-month and five-year lifespans for series A and B, respectively.
Reviva estimates that it will require up to $70 million to complete the RECOVER-2 trial and sustain operations until approval. The recent capital raise is a significant step towards this goal, with the company also exploring additional funding sources, including potential partnerships.
Conclusion
The preliminary OLE data for brilaroxazine underscores its potential as a well-tolerated and effective antipsychotic treatment. With the RECOVER-2 trial on the horizon and a successful capital raise, Reviva Pharmaceuticals is well-positioned to advance its clinical development program and bring brilaroxazine closer to market approval.
