There is currently no FDA-approved treatment for RSV infection, so biotech companies are targeting various viral components in an attempt to find ways to stop it.Enanta Pharmaceuticals’ drug the furthest in clinical development for a specific target just Failed exam in low-risk RSV patients. However, the biotech company believes its drug may still help patients with more severe or immunocompromised conditions, and is continuing to study these high-risk groups.
The drug, EDP-938, is being tested in a Phase 2b study enrolling otherwise healthy patients with community-acquired RSV. Watertown, Massachusetts-based Enanta announced after the market closed Wednesday that the drug fell short of its primary goal of reducing overall symptoms compared with a placebo. The drug has not yet met its secondary antiviral targets in clinical trials.
RSV affects the lungs and causes symptoms similar to the common cold. In healthy people, these symptoms are mild, and the infection usually resolves after a few days. Jay Luly, the biotech’s president and chief executive, said that may be one reason why the Phase 2b trial of Enanta’s drug was unsuccessful.
“Although patients were treated within 48 hours of symptom onset, a key observation of this study was that viral load and symptoms had peaked and were declining at the time of the first dose, suggesting that RSV infection in this otherwise healthy quickly receded from the crowd,” he said in a prepared statement.
Still, investors didn’t like these preliminary results. Shares of Enanta opened Thursday at $38.02, down 17% from Wednesday’s close.
EDP-938 is a small molecule designed to block the RSV N protein, which is part of the viral replication pathway. In results reported in a 2019 Phase 2a challenge study in healthy adults, the drug was statistically significant for RSV viral load, symptoms and mucus compared with placebo. Based on these results, the company began a Phase 2b study in non-hospitalized adults with RSV infection. The trial enrolled 81 adults who were randomly assigned to receive either Enanta’s drug or a placebo for 5 days. Of these patients, 66 to 33 in each group were later confirmed to be RSV positive by PCR testing.
Despite failing to show the primary goal of symptom improvement during the 14-day follow-up period, Enanta noted that patients’ RSV RNA levels trended toward undetectable levels compared to placebo, which was statistically significant on day 5 of treatment . The company also noted that the drug’s safety profile in the latest clinical trial was consistent with earlier trials. Based on these results, research in high-risk patient groups continues.
Enanta said recruitment is ongoing for a Phase 2 placebo-controlled study in hospitalized and non-hospitalized pediatric RSV patients. A separate Phase 2b study is also continuing in adult hematopoietic stem cell transplant recipients with symptoms of acute RSV infection and upper respiratory tract infection. Both studies are expected to continue into next year, Enanta said. The company also plans to begin a third interim study in more high-risk patients: older adults and those with asthma, chronic obstructive pulmonary disease or congestive heart failure. The Phase 2b study is expected to begin by the end of this year.
Other approaches to RSV are looking for different targets, fusion proteins key to the virus’s entry into cells.The F protein project that has gone farthest clinically belongs to ArkBio, which report In April, its drug candidate met the primary and secondary goals of a pivotal test. The Shanghai-based biotech company said it plans to file an application with Chinese regulators by the middle of this year. Meanwhile, UK-based ReViral’s oral F-protein inhibitor sisunatovir has entered mid-stage testing. last month, Pfizer reaches deal to acquire ReViral, deal could be as high as $525 million, including milestone payments. Re-Viral’s pipeline also has an N-protein inhibitor that has reached early clinical development.
Enanta’s EDP-938 is the most advanced program in the company’s product line. The biotechnology has a commercial product. Enanta’s antiviral drug glecaprevir is part of the combination drug Mavyret, marketed by AbbVie to treat hepatitis C. In RSV, Enanta doesn’t put all its eggs in the N protein basket. Another drug candidate, EDP-323, is designed to block RSV’s L protein, which contains enzymes needed for viral replication. Enanta said EDP-323 has shown efficacy against RSV-A and RSV-B strains in laboratory tests and is not expected to develop cross-resistance with other classes of drugs, making it possible to use it alone or with other drugs, including EDP-938. Phase 1 testing of EDP-323 is expected to begin in the second half of this year, the company said.
Public domain image from the Centers for Disease Control and Prevention
