공고 • May 19
Enanta Pharmaceuticals Reports Topline Data from the RSVP Study of EDP-938 in Otherwise Healthy Adults with Community-Acquired Respiratory Syncytial Virus (RSV)
Enanta Pharmaceuticals, Inc. reported topline results for RSVP, its Phase 2b study evaluating EDP-938, a potent N-protein inhibitor, in otherwise healthy adults with community-acquired RSV. In this low-risk patient population which had mild, self-resolving upper respiratory tract infection, EDP-938 did not meet the primary endpoint of reduction in total symptom score compared to placebo, or the secondary antiviral endpoints. However, a statistically significant difference in the number of subjects achieving undetectable RSV RNA at the end of treatment at Day 5 was observed with EDP-938 compared to placebo (p=0.033). Further, EDP-938 demonstrated a favorable safety profile, consistent with that observed in approximately 500 subjects exposed to date. Enanta continues to evaluate EDP-938 in high-risk populations in ongoing and planned clinical studies, including pediatric patients, adult hematopoietic cell transplant recipients, and a high-risk adult population, all of which have the most significant unmet need. RSVP was a Phase 2b, randomized, double-blind, multicenter, placebo-controlled study in ambulatory adults with or without comorbidities aged 18 to 75 years with confirmed RSV infection within 48 hours of symptom onset. Patients were randomized 1:1 to receive once-daily 800 mg EDP-938 or placebo for 5 days and followed until Day 14. The primary objective of the study was to evaluate the effect of EDP-938 on progression of RSV infection by assessment of clinical symptoms measured over the 14-day study period. The secondary objectives evaluated the antiviral efficacy, safety, and pharmacokinetics of EDP-938. A total of 81 patients were randomized and dosed and included in the intent-to-treat (ITT) analysis. The modified ITT efficacy analysis included only the 66 patients (33 in each group) that were subsequently confirmed to be RSV positive using a central RT-PCR test. Demographics and baseline characteristics were well balanced between the two arms, except for the median RSV viral load (5.9 and 7.1 log10 copies/mL, in EDP-938 and placebo, respectively). Overall, most of the patients were female, White, non-Hispanic, young (median age approximately 50 years old) and had a normal frailty scale score, consistent with a healthy population as per the eligibility criteria of the study. Only eight patients were 65 years or older (n=3 in EDP-938, n=5 in placebo), and a total of seven patients (n=4 in EDP-938, n=3 in placebo) had stable asthma and/or chronic obstructive pulmonary disease (COPD), at entry. The primary endpoint, total symptom score (TSS) area under the curve (AUC) from Day 1 through Day 14, was not met. The AUC for the mean total symptom score (days x score) was not statistically different between the two groups (p=0.256). Although, the secondary antiviral endpoints were not met, a trend in favor of EDP-938 was observed with regard to the percentage of subjects achieving undetectable RSV RNA, with a statistically significant difference observed at the end of treatment at Day 5 (p=0.033). A total of 11 (27%) patients in both the EDP-938 and placebo arms reported treatment-emergent-adverse events. Most of the adverse events (AEs) were mild and not related to study drug. There were no severe or serious AEs, and no discontinuations due to AEs. In the study, the observed safety profile was consistent with previous clinical studies. Good EDP-938 exposures were achieved and were consistent with those observed in treated subjects in previous studies. Data from RSVP will be presented at a future medical meeting or in a peer-reviewed publication. Recruitment is ongoing for RSVPEDs, a Phase 2 randomized, double-blind, placebo-controlled study in hospitalized and non-hospitalized pediatric RSV patients, and RSVTx, a Phase 2b, randomized, double-blind, placebo-controlled study in adult hematopoietic cell transplant recipients with acute RSV infection and symptoms of upper respiratory tract infection. The company expects these studies to continue into 2023. Further, the company plans to initiate an additional Phase 2b study in a high-risk adult population, including the elderly and/or those with asthma, COPD, or congestive heart failure, by year-end. Finally, Enanta is on track to initiate a Phase 1 study for EDP-323, a novel, oral, direct-acting antiviral selectively targeting the RSV L-protein, in the second half of 2022. EDP-323 has shown sub-nanomolar potency against RSV-A and RSV-B in vitro and is not expected to have cross resistance to other classes of inhibitors. EDP-323 could be used as a monotherapy or in combination with other RSV mechanisms, such as EDP-938, to potentially broaden the addressable patient populations or their treatment windows. EDP-938, Enanta’s lead N-protein inhibitor, is being developed for the treatment of RSV infection, and has been granted Fast Track designation by the U.S. Food and Drug Administration. EDP-938 is a nanomolar inhibitor of both RSV-A and RSV-B activity. EDP-938 is differentiated from RSV fusion inhibitors as the N-protein inhibitor targets the virus’ replication machinery and has demonstrated a high barrier to resistance in vitro. In preclinical studies, EDP-938 maintained antiviral potency across all clinical isolates tested and was active against viral variants resistant to other mechanisms. EDP-938 demonstrated a favorable safety, pharmacokinetic and drug-drug interaction profile in an extensive Phase 1 program. In a Phase 2 challenge study, EDP-938 achieved highly statistically significant (p<0.001) reductions in RSV viral load and clinical symptoms compared to placebo, and was safe and well-tolerated with infrequent AEs. EDP-938 is currently being evaluated in RSVPEDs, a Phase 2 study in pediatric RSV patients, and RSVTx, a Phase 2b study in adult hematopoietic cell transplant recipients with RSV. RSV is the most common cause of bronchiolitis (inflammation of the small airways in the lung) and pneumonia in children under one year of age in the U.S. and a significant cause of respiratory illness in older adults and immunocompromised individuals.1 According to the Centers for Disease Control and Prevention, virtually all children in the United States get an RSV infection by the time they are two years old and one to two out of every 100 children younger than six months of age with RSV infection may need to be hospitalized.2 Globally, there are an estimated 33 million cases of RSV annually in children less than five years of age, with about 3 million hospitalized and up to approximately 120,000 dying each year from complications associated with the infection.3 RSV represents a significant health threat for adults older than 65 years of age, with an estimated 177,000 hospitalizations and 14,000 deaths associated with RSV infections annually in the United States.
