Enanta Pharmaceuticals’ COVID-19 drug reduced some symptoms of the respiratory disease but did not reduce viral load or time to improvement when compared to placebo. Executives pointed to a tighter analysis of key symptoms for signs that EDP-235 could have value on the market—so long as a partner helps them get there.
EDP-235 was tested in 190 standard risk patients with mild to moderate COVID-19 in the phase 2 SPRINT trial. Enanta reported a dose-dependent improvement in symptoms for the 400-mg dose arm when compared to placebo, which was the main goal of the trial, according to a Monday afternoon press release. The treatment effect started as soon as one day after dosing.
But EDP-235 did not reduce the time to improvement on 14 symptoms or lower the viral load as measured via the nose. Enanta blamed the viral load miss on the rapid viral decline in the placebo arm. This has plagued a number of late starters to the COVID-19 clinic, as trials that got underway later in the pandemic met a mutated virus and clinical endpoints became irrelevant.
“The patient population … since the beginning of the pandemic has changed dramatically, as has the virus. So, you know, good for the humans—the seropositivity that we’re building up over time either through natural infection or vaccination or both,” CEO Jay Luly, Ph.D., told investors on a Monday afternoon earnings call.
Patients came into Enanta's trial with higher natural immunity, either from vaccination, infection or both, according to Tara Kieffer, Ph.D., senior vice president of new product strategy and development. Studies like Enanta's have seen viral loads dropping naturally, without aid from a therapeutic, which can impact the outcome of a study.
Enanta's shares fell 28% as the market opened Tuesday to $24.52 compared to a close of $34.33 on Monday.
Nevertheless, EDP-235 “could play an important role in the treatment of COVID-19,” since it had an impact on clinically meaningful endpoints, Luly said. On the viral load miss, Luly said that the FDA does not look at viral load when approving COVID therapeutics, so Enanta’s therapy could still find regulatory success for improving symptoms. A drug for standard risk patients would look at symptom reduction—which EDP-235 has demonstrated—and hospitalizations and death would be considered for higher risk patients, Luly explained.
“At the end of the day, the agency doesn’t approve any of the COVID drugs based on viral load, it’s based on other endpoints,” Luly said. Enanta plans to talk to the FDA “as a matter of course” and finish up the study, he added.
EDP-235’s impact on symptoms will form the basis of conversations with regulators, Chief Medical Officer Scott Rottinghaus, M.D., said. But Enanta will need to find a pharma partner to continue development, which has always been the plan, according to Luly.
To make the case for a partner, Enanta compared EDP-235 with Shionogi’s protease inhibitor ensitrelvir, which is approved in Japan and just received fast-track designation from the FDA. That drug was studied in a 341-patient phase 2 and also looked at symptoms but was conducted in a population that had a higher viral load at baseline. Enanta argued that symptom improvement was similar for both antivirals.
EDP-235 could be developed and tested in several COVID-related indications, such as long COVID or as a prophylaxis, Luly said. Enanta has picked 400 mg as the dose that will move forward in any future studies.
“In order to realize this vision, we feel a pharma partnership will better enable us to get the best registration program to achieve that optimal label, so that’s going to be our focus for phase 3,” Luly said.
Enanta executives pointed to key subgroups and additional analyses that were conducted to further pad the case, despite the mixed readout.
On the symptoms, Rottinghaus said a prespecified analysis showed that if the symptoms are whittled down to six key ones, the 400-mg dose had a greater improvement than placebo and was statistically significant. So, the time to improvement was not met for all 14 symptoms, but if you pick out six select respiratory and systemic symptoms—including shortness of breath, sore throat, headache and chills—patients receiving EDP-235 improved two days faster.
Enanta also reported fiscal second-quarter earnings for the period ending March 31 on Monday, including royalty revenue of $17.8 million from worldwide net sales of Mavyret, which is marketed by AbbVie for hepatitis C. The biotech reported cash and equivalents of $225.1 million as of March 31, which should last into 2026.