ReViral
Proactive Biomedical Frontiers in Virolotheraphy

Respiratory syncytial virus (RSV) infections claim a substantial number of lives across the world each year. While antivirals, vaccines, and monoclonal antibodies are being developed as preventative and therapeutic treatments, little is known about the worldwide molecular epidemiology of RSV. However, several unanswered medical concerns about RSV exist despite enormous global research efforts spanning decades focused on the virus. Potential treatments have had a difficult time showing a favourable safety profile or effectiveness in the past. The statistics speak for themselves—there are currently no FDA-approved RSV treatments for adults and only two for at-risk toddlers. Unfortunately, even those have significant drawbacks, such as restricted labelling, exorbitant prices, limited antiviral efficacy, and concerns about toxicity. ReViral, with a focus on RSV, develops transformational antiviral therapeutics to help the world’s most at-risk population.

Founded in 2011, ReViral is a clinical-stage biopharmaceutical business dedicated to developing and commercializing antiviral medicines, initially for the treatment of RSV. With the help of an expert team, the company is developing RV521 (REVIRAL1), a unique, highly potent small-molecule inhibitor of RSV fusion that has completed Phase 1 clinical trials and demonstrated considerable efficacy in Phase 2 clinical trials in adult volunteers. RV521 is reportedly moving towards phase 2 trials in infants and adult patients.

REVIRAL1 is a three-part global adaptive study that can evaluate the safety, toxicities, pharmacokinetic (PK) profile, the antiviral and clinical impact of single and multiple dosages of Sisunatovir in otherwise healthy infants aged 1 to 36 months that are hospitalized with RSV lower respiratory tract complications.

Part A of the research is an open-label, single-dose phase aimed to assess safety and PK. Part B’s goal is to evaluate the safety and antiviral efficacy in the double-blind, placebo-controlled stage of the research, in which patients will be put on medications or placebo (3:1 randomization) twice daily for five days. Part C is a randomly selected, double-blind, placebo-controlled segment of the research that evaluates antiviral activity and clinical outcomes in patients who were randomly assigned to one of three intervention groups (placebo, low-dose, or high-dose Sisunatovir).

Sisunatovir, the company’s primary product candidate, is an orally administered fusion inhibitor that is actively being analyzed in two global multicenter phase 2 clinical studies. One being in a pediatric patient population (REVIRAL1) and the second one in an adult stem-cell transplant patient population (REVIRAL2). The business is also working on an N-protein replication inhibitor program that is approaching the end of preclinical testing. In both cases, the programs have been developed in-house, and ReViral has kept the worldwide development and commercialization rights for them. Sisunatovir works by blocking F-mediated fusion with the host cell, which prevents RSV replication. More recently, the US Food and Drug Administration (FDA) granted the product a fast-track approval. Preclinical studies revealed that Sisunatovir has a positive safety profile and a potential therapeutic index.

In addition to the aforementioned competencies, Sisunatovir was proven to be safe and effective in phase 1 clinical trials, achieving the desired exposure levels with no serious adverse effects. Furthermore, in 2018, the outcomes of a phase 2a human challenge research in healthy adult volunteers infected with RSV were presented, indicating that Sisunatovir reduced viral load and improved clinical symptoms statistically significantly. In addition to the REVIRAL1 research, ReViral has recently commenced a worldwide phase 2 clinical trial of Sisunatovir in an adult stem-cell transplant population (REVIRAL2).

Backed by seasoned professionals with a proven track record in the virology and biopharma sectors, the company is making groundbreaking strides in minimizing RSV fatality rates. Currently, ReViral is conducting IND-enabling research on an RSV N-protein replication inhibitor. The company’s most recent milestones include the release of the data safety monitoring committee’s positive recommendation to continue the phase 2 clinical study of Sisunatovir for the treatment of RSV infections in hospitalized infants.