Enanta weakens on RSV treatment trial readout

Shares in Enanta Pharma were sliding this morning after the US company reported results of a phase 2b trial of its respiratory syncytial virus (RSV) treatment zelicapavir that missed the primary endpoint.

The statement on the results buried the news that zelicapavir was unable to outperform placebo in total symptom scores – the time to resolution of a lower respiratory tract disease (LRTD) subset of four RSV-related symptoms to mild – and emphasises a series of other, secondary endpoints that improved with the drug.

Investors were spooked by the miss, and shares in Nasdaq-listed Enanta were down around 11%, having risen sharply in anticipation of the readout of the RSVHR trial, which enrolled patients with RSV. Zelicapavir is a small-molecule antiviral that is designed to interfere with RSV's ability to replicate itself.

Among the positive findings was an improvement of 6.7 days in the time to complete resolution of all RSV symptoms in a subgroup of patients who were vulnerable to severe complications due to their age (75+), congestive heart failure (CHF), or chronic obstructive pulmonary disease (COPD).

For the total study population, which included 186 RSV patients aged 18 and over, the reduction compared to placebo was 2.2 days, according to Enanta. The vulnerable patients accounted for more than 80% of the study's enrolment.

Enanta also pointed to a statistically significant increase in Patient Global Impression of Severity (PGI-S) score, a lower hospitalisation rate with the drug, and a faster median time to undetectable viral load compared to placebo.

The company's chief medical officer, Scott Rottinghaus, said he is "highly encouraged" by the results as they represent the first time that an RSV antiviral has shown a clinical benefit in "high-risk adult outpatients."

He added: "We believe the totality of [this] data provides strong rationale for further clinical advancement of zelicapavir […] as a broadly effective, first-in-class RSV treatment."

At the moment, FDA-approved drugs for RSV are mainly used to prevent infections in infants and young children, and there are three vaccines approved to protect older adults from GSK, Pfizer, and Moderna.

One older antiviral – ribavirin – is approved for treating acute infections, although its efficacy is questionable and it has been linked to potentially serious side effects, including bronchospasm, dyspnoea, chest pain, rash, and conjunctivitis.

Enanta has another shot on goal in RSV treatment with EDP-323, another antiviral that cleared a phase 2a trial last year, and could also be a companion to zelicapavir for combination treatment.