Sisunatovir (RV521): A Comprehensive Post-Mortem Analysis of a Promising RSV Fusion Inhibitor

Executive Summary

Sisunatovir, also known by its development code RV521, emerged as a highly promising investigational therapeutic for the treatment of Respiratory Syncytial Virus (RSV) infections. As an orally bioavailable small molecule, it was designed to inhibit the RSV fusion (F) protein, a critical component for viral entry into host cells.[1] Its potent preclinical profile, demonstrating broad activity against both RSV-A and RSV-B subtypes, and successful human proof-of-concept data from a challenge study positioned it as a leading candidate to address a significant unmet medical need in vulnerable populations, including infants and high-risk adults.[4]

The considerable potential of sisunatovir culminated in the strategic acquisition of its originator, the clinical-stage biopharmaceutical company ReViral, by Pfizer Inc. in June 2022. The deal, valued at up to $525 million, underscored the high commercial expectations for the asset and was a key component of Pfizer's strategy to build an end-to-end RSV franchise, pairing sisunatovir as a treatment with its own vaccine candidate for prevention.[7]

Despite this momentum and a Fast Track designation from the U.S. Food and Drug Administration (FDA), the entire clinical development program for sisunatovir was abruptly terminated by Pfizer in October 2024.[8] The company cited "ongoing challenges" as the rationale, specifically highlighting a critical drug-drug interaction (DDI) with antacids, while clarifying that the decision was not driven by safety concerns.[8]