Enanta's RSV Drug Misses Primary Endpoint in Phase 2b Trial, but Shows Promise in Secondary Analyses

Enanta Pharmaceuticals has reported mixed results from a phase 2b trial of its oral, direct-acting antiviral drug candidate, zelicapavir, for the treatment of respiratory syncytial virus (RSV). While the study failed to meet its primary endpoint, secondary analyses and subgroup data have provided encouraging signals that may support further development.

Primary Endpoint Missed, but Secondary Analyses Show Potential

The trial, which enrolled 186 patients, narrowed its efficacy population to 175 RSV-positive individuals as confirmed by central laboratory testing. Participants were randomized to receive either zelicapavir or placebo once daily for five days, with a 28-day follow-up period.

The primary endpoint, measuring the time to resolution of RSV lower respiratory tract disease (LRTD) symptoms, was not met. Zelicapavir showed only a 0.5-day improvement over placebo in the efficacy population, which was not statistically significant.

However, secondary analyses painted a more promising picture:

• All 13 RSV symptoms cleared up 2.2 days faster in the zelicapavir group compared to placebo.
• When considering all 29 parameters in a patient-reported respiratory infection tool, symptoms resolved 3.6 days faster with zelicapavir treatment.

Subgroup Analyses Reveal Stronger Efficacy Signals

Notably, subgroup analyses focusing on high-risk patients showed more substantial benefits from zelicapavir treatment. These subgroups, which comprised 81% of the study population, included patients with congestive heart failure, chronic obstructive pulmonary disease, or those aged 75 years or older.

In these high-risk subgroups:

• Time to resolution of LRTD symptoms improved by three days with zelicapavir.
• Time to resolution of all 13 RSV symptoms was 6.7 days shorter in the zelicapavir group.
• Considering all 29 respiratory infection parameters, the difference increased to 7.2 days in favor of zelicapavir.

Safety and Future Development

The trial also revealed a potential benefit in reducing hospitalizations, with rates of 1.7% for zelicapavir versus 5% for placebo. This data, combined with the positive secondary endpoint results, has bolstered Enanta's confidence in the drug's potential.

Dr. Scott Rottinghaus, Chief Medical Officer of Enanta, stated, "We believe the totality of these data provides strong rationale for further clinical advancement of zelicapavir. Importantly, we identified multiple potential registrational endpoints for a phase 3 trial."

Despite the optimism from Enanta's leadership, the market response was cautious, with the company's shares falling 10% in premarket trading to $7.08 following the announcement.

As the pharmaceutical industry continues to seek effective treatments for RSV, Enanta's zelicapavir remains a candidate to watch, with its oral formulation potentially offering advantages over other therapies in development. The company's next steps will be crucial in determining whether this promising antiviral can overcome its initial setback and progress to phase 3 trials.