WATERTOWN, Mass. — Enanta Pharmaceuticals Inc., a clinical-stage biotechnology company developing treatments for viral infections and immunological diseases, announced that the first patient has been dosed in its global Phase 2b/3 RESOLVE clinical trial evaluating zelicapavir, an investigational antiviral treatment for respiratory syncytial virus (RSV).
The study will assess the drug’s ability to shorten the duration of RSV symptoms and reduce hospitalization rates among adults at increased risk of severe complications.
Enanta expects to report topline results from the Phase 2b portion of the trial in 2027.
RSV is a common respiratory virus that can cause serious illness in older adults and individuals with underlying medical conditions, including chronic obstructive pulmonary disease (COPD) and congestive heart failure.
Although preventive RSV vaccines are available for certain populations, there are currently no approved antiviral medications specifically designed to treat RSV infections.
“We are excited to advance our zelicapavir program into a Phase 2b/3 study with the dosing of the first patient in RESOLVE,” said Dr. Scott T. Rottinghaus, chief medical officer of Enanta Pharmaceuticals.
“Based on learnings from our Phase 2 RSVHR study, the RESOLVE trial is enrolling adults at high risk for severe outcomes from RSV. These patients with congestive heart failure, chronic obstructive pulmonary disease, or age of 75 or older have substantial disease burden and the potential to benefit from an RSV treatment,” Rottinghaus added.
The RESOLVE trial is a randomized, double-blind, placebo-controlled study involving adult outpatients who have tested positive for RSV and experienced respiratory symptoms for no more than three days.
Eligible participants must be at least 75 years old or have COPD or congestive heart failure.
Patients will receive either 800 milligrams of oral zelicapavir or a placebo once daily for seven days, followed by 28 days of evaluation.
The study’s primary endpoint will measure the time required for complete resolution of 13 RSV-related symptoms. A key secondary endpoint will assess hospitalization rates, while additional measures will evaluate antiviral activity, clinical effectiveness and safety.
The Phase 2b portion of the study will enroll at least 200 patients to confirm the treatment effects observed in earlier research. The Phase 3 portion is expected to include approximately 660 participants.
Previous Phase 2 findings suggested that zelicapavir could significantly shorten symptom duration among high-risk adults.
In Enanta’s earlier RSVHR trial, patients who were 75 or older or had COPD or congestive heart failure experienced complete resolution of RSV symptoms approximately 6.7 days sooner with zelicapavir than with placebo.
The company also reported an RSV-related hospitalization rate of 0% among zelicapavir-treated patients in this subgroup, compared with 5% among those receiving placebo.
These findings will require confirmation in the larger RESOLVE study.
“The Phase 2b portion is designed to confirm the treatment effect size and generate an additional dataset with the goal of strengthening the clinical evidence supporting zelicapavir,” Rottinghaus said.
“Together with LOTUS, our pediatric Phase 2b trial, this progress positions us to deliver two important Phase 2b data readouts in 2027 and marks a significant step forward in the development of zelicapavir,” he added.
Zelicapavir is an investigational oral antiviral designed to inhibit the RSV nucleoprotein, known as the N-protein, which plays an essential role in viral replication.
Unlike RSV fusion inhibitors, which target the virus’s ability to enter cells, zelicapavir is designed to interfere with viral replication after infection.
The drug has demonstrated antiviral activity against both major RSV subtypes, RSV-A and RSV-B, in laboratory studies.
Earlier clinical research involving hospitalized and non-hospitalized children between 28 days and three years old also showed antiviral activity and shorter times to symptom resolution.
According to Enanta, zelicapavir has demonstrated a favorable safety and tolerability profile in more than 700 individuals who have received the drug during clinical development.
Dr. Juan Antonio Carmona Herrera, a principal investigator in the RESOLVE study and president of C&A Clinical Trials Corp., said the development of an effective RSV antiviral could address a significant gap in treatment options.
“RSV remains a significant cause of illness, particularly among older adults and individuals with underlying health conditions who are at heightened risk of severe disease. Despite RSV’s burden, there are no treatment options available,” Herrera said.
“An effective antiviral has the potential to change the way RSV is managed by directly targeting the virus, with the goal of reducing disease severity, preventing complications, and improving patient outcomes,” he added.
The U.S. Food and Drug Administration has granted zelicapavir Fast Track designation, which is intended to facilitate the development and review of treatments addressing serious medical conditions with unmet needs.
Enanta is also evaluating the drug in its Phase 2b LOTUS pediatric trial, with results from both studies expected in 2027.
If successful, zelicapavir could become one of the first antiviral treatments specifically approved for RSV infection, offering a therapeutic option beyond existing preventive measures.
