Enanta sinks to multiyear low as phase 2b RSV trial flames out

Enanta Pharmaceuticals’ bid to treat low-risk respiratory syncytial virus (RSV) patients has gone off the rails. The failure of the phase 2b trial of N-protein inhibitor EDP-938 in the population sent Enanta’s stock to its lowest ebb since 2017 but failed to extinguish the biotech’s belief in the prospect in other settings.

The phase 2b clinical trial randomized and dosed 81 otherwise healthy adults with community-acquired RSV. In that low-risk population, EDP-938 failed to reduce total symptom score compared to placebo, the primary endpoint. The study also missed secondary antiviral endpoints, causing Enanta’s stock to fall 16% in premarket trading to around $38.50. Enanta last traded below $40 in 2017.

In the absence of success against those endpoints, Enanta pointed to a statistically significant difference in the number of subjects having undetectable RSV RNA at the end of treatment at Day 5 and the lack of safety red flags as positives. 

Enanta expects to achieve better results in high-risk populations. Investigators in the phase 2b study treated participants within 48 hours of symptom onset. Even so, Enanta said their viral load and symptoms had already peaked. Higher-risk patients may be less able to rapidly fight off infection without treatment.

“These patients have reduced RSV immunity which manifests in a higher and longer duration of viral load and greater disease severity, allowing a bigger window to realize the full potential of EDP-938. Moving forward, our broad clinical development plan is focused on evaluating EDP-938 in populations with the greatest unmet need, namely those who are at high-risk for severe disease,” Enanta CEO Jay Luly said in a statement. 

Enanta’s clinical development strategy covers infants and young children, the immunocompromised, the elderly and patients with chronic heart or lung disease. The pediatric and immunocompromised studies are already enrolling and set to continue into 2023. Enanta plans to start a phase 2b clinical trial in other high-risk adults, such as the elderly and asthma patients, by the end of the year.

The strategy reflects Enanta’s belief that EDP-938 is the pick of the RSV antivirals in late-phase trials. The biotech is up against two fusion inhibitors, Ark Biopharmaceutical’s ziresovir and ReViral’s sisunatovir. Johnson & Johnson moved its own fusion inhibitor into phase 3 late in 2020 but recently terminated two studies on the candidate. Enanta has removed the candidate, rilematovir, from its list of rivals.