Enanta's RSV antiviral crushes viral load in challenge study

Enanta Pharmaceuticals has linked its respiratory syncytial virus (RSV) antiviral to significant reductions in viral load and symptoms in a phase 2a challenge study. The biotech said the results cleared the bar set by its other candidate, opening up opportunities to test the molecules as single agents and in combination.

Previously, Enanta reported data from a challenge study of its N-protein inhibitor zelicapavir. The data led to further development of the candidate. In parallel, Enanta advanced a L-protein inhibitor, EDP-323. The EDP-323 challenge study had essentially the same design as the zelicapavir trial and was run at the same location, potentially allowing Enanta to make a more accurate comparison than is typically possible.

Scott Rottinghaus, M.D., chief medical officer at Enanta, said in a statement that the EDP-323 data raise “the high bar set by zelicapavir.” In a study of 142 healthy adults inoculated with RSV, EDP-323 lowered viral load area under the curve (AUC) by 85% at the high dose and 87% at the low dose compared to placebo.

Those reductions caused the trial to meet its primary endpoint. Enanta also reported hits on two of the secondary endpoints. The biotech linked the two doses of EDP-323 to reductions in viral culture AUC of 98% and 97% compared to placebo; and to symptom reductions of 66% on the high dose and 78% on the low dose, again compared to placebo.

Enanta’s press release lacks a discussion of the next steps, beyond a high-level reference to the potential for the distinct mechanisms of EDP-323 and zelicapavir to support single-agent and combination studies. Tara Kieffer, Ph.D., chief product strategy officer at Enanta, provided additional details of how the two molecules may be used at an event run by Cantor Fitzgerald last week.

Kieffer said hard-to-treat patients, such as people who are severely immunocompromised, may benefit from combination therapy. Combining the drugs could also support use of the antivirals longer after the start of symptoms.

Clinical data on zelicapavir are due in the fourth quarter. The back-to-back data drops will allow Enanta “to take a look at the portfolio and make the best decisions about how we might move forward these compounds,” Kieffer said.

The compounds are moving toward a market that is already served by RSV vaccines that can prevent infection and, in doing so, reduce the number of people who may need an antiviral. However, Enanta sees an ongoing need for antivirals in both the pediatric and adult populations, with Kieffer saying babies and children will go on to get RSV infection after protection wanes and noting low vaccine use in adults.