Enanta Pharmaceuticals Reports Positive Topline Results from Phase 2 SPRINT Trial Evaluating EDP-235 in Standard Risk Patients with COVID-19
- Study Met Primary Endpoints of Safety and Tolerability
- Dose-Dependent Improvement in Total Symptom Score Observed with EDP-235 Treatment Compared to Placebo, Achieving Statistical Significance as Early as One Day After First Dose
- No Difference in Viral Load Reduction; Rapid Decline Observed in All Study Arms
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EDP-235 met the primary endpoint of the trial and was generally safe and well-tolerated. A dose-dependent improvement in symptoms was observed with EDP-235 treatment compared to placebo, which achieved statistical significance (p<0.05) in the 400mg treatment group at multiple time points, starting as early as one day after the first dose. In a prespecified population consisting of patients enrolled within 3 days of symptom onset, a statistically significant improvement was observed with EDP-235 at 400mg at all time points. While no difference was observed in time to improvement of 14 targeted COVID-19 symptoms, an analysis of a subset of these symptoms showed a 2-day shorter time to improvement in patients receiving EDP-235 400mg who were enrolled within 3 days of symptom onset (p<0.01). No effect on virologic endpoints as measured in the nose was detected due to the rapid viral decline in the placebo arm of this highly immunologically-experienced, standard risk population.
“The data from our Phase 2 SPRINT trial demonstrated a favorable safety profile and an improvement in clinical symptoms, suggesting that EDP-235 may have an impact on clinically meaningful endpoints,” said
EDP-235 SPRINT Phase 2 Study Topline Results
SPRINT was a Phase 2, randomized, double-blind, placebo-controlled study in non-hospitalized, symptomatic patients with mild to moderate COVID-19 who were not at an increased risk for severe disease. The primary objective of the study was to evaluate the safety and tolerability of EDP-235, with key secondary objectives of symptoms, antiviral activity, and pharmacokinetics of EDP-235.
A total of 231 subjects were randomized 1:1:1 to receive 200mg or 400mg EDP-235 or placebo orally once daily for 5 days (n=77 in 200mg, n=78 in 400mg, n=76 in placebo) and followed through Day 33. The modified intent-to-treat efficacy analysis included treated patients who were subsequently confirmed to be COVID-19 positive using a central RT-PCR test (n=62 in 200mg, n=67 in 400mg, n=61 in placebo). An additional prespecified population of patients who were randomized within 3 days after the onset of symptoms was evaluated (n=47 in 200mg, n=47 in 400mg, n=45 in placebo). Demographics and baseline characteristics were well balanced between the arms. Overall, most of the patients were White, Hispanic, young (median age approximately 45 years old), body mass index of around 25 kg/m2, enrolled within 3 days of symptom onset (approximately 73%), and seropositive (approximately 95%).
EDP-235 at 200mg or 400mg was generally safe and well-tolerated in patients receiving 5 days of dosing. A low frequency of treatment emergent adverse events (TEAEs) was observed (1.3% and 6.4% in the EDP-235 200mg and 400mg arms, respectively, vs. 2.6% in placebo). Most TEAEs were mild in severity, with no serious TEAEs or discontinuations due to TEAEs. Laboratory values were generally unremarkable, although one patient receiving EDP-235 400mg who also used concomitant alcohol and acetaminophen experienced transient asymptomatic elevation of ALT (grade 4), AST (grade 3) and GGT with normal bilirubin and alkaline phosphatase. Transient elevations in total cholesterol and triglycerides were seen with EDP-235 treatment, trending toward baseline after completion of treatment.
A dose-dependent improvement in the key secondary endpoint of total symptom score (TSS) was demonstrated in patients treated with EDP-235 compared to placebo, despite the lack of virologic effect as measured in the nose. This improvement achieved statistical significance (p<0.05) in the 400mg treatment group at multiple time points, starting as early as one day after initiation of EDP-235 treatment. In the prespecified patient population enrolled within 3 days of symptom onset, a statistically significant improvement in TSS was observed with EDP-235 400mg compared to placebo at all measured time points (Days 1 -32 post dosing). While no difference was observed in time to improvement of 14 targeted COVID-19 symptoms, an analysis of a subset of 6 of these symptoms showed a 2-day shorter time to improvement in patients receiving EDP-235 400mg who were enrolled within 3 days of symptom onset (p<0.01 versus placebo).
Key secondary endpoints evaluating virologic effect were not met. No difference was observed between patients treated with EDP-235 and placebo in viral RNA decline or infectious viral load, likely due to the rapid viral decline in the placebo arm of this trial’s seropositive, standard risk population. The mean baseline viral load in this study population was approximately 5 log, and a precipitous decrease in viral RNA was observed in all study arms, indicating this highly immune population rapidly cleared virus from the nose. An additional analysis of patients with a baseline viral load greater than 5 log showed a decline of 0.4 log at Day 3 in both EDP-235 treatment arms compared to placebo.
EDP-235 displayed pharmacokinetic profiles at the 200mg and 400mg doses consistent with previous studies, demonstrating 7x and 12x multiples over the protein-adjusted EC90.
Full data from SPRINT will be presented at a future medical meeting or in a peer-reviewed publication.
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Enanta is using its robust, chemistry-driven approach and drug discovery capabilities to become a leader in the discovery and development of small molecule drugs for the treatment of viral infections. Enanta’s research and development programs include clinical candidates for the following disease targets: respiratory syncytial virus (RSV), SARS-CoV-2 (COVID-19) and hepatitis B virus (HBV). Enanta is also conducting research on a single agent targeting both RSV and human metapneumovirus (hMPV).
Enanta receives royalties from hepatitis C virus (HCV) products developed under its collaboration with AbbVie. Glecaprevir, a protease inhibitor discovered by Enanta, is part of one of the leading treatment regimens for curing chronic HCV infection and is sold by AbbVie in numerous countries under the tradenames MAVYRET® (
Forward Looking Statements
This press release contains forward-looking statements, including statements with respect to the prospects for further development of EDP-235. Statements that are not historical facts are based on management’s current expectations, estimates, forecasts and projections about Enanta’s business and the industry in which it operates and management’s beliefs and assumptions. The statements contained in this release are not guarantees of future performance and involve certain risks, uncertainties and assumptions, which are difficult to predict. Therefore, actual outcomes and results may differ materially from what is expressed in such forward-looking statements. Important factors and risks that may affect actual results include: the impact of development, regulatory and marketing efforts of others with respect to competitive treatments for COVID-19; the discovery and development risks for EDP-235; any continuing impact of the COVID-19 pandemic on business operations and clinical trials; Enanta’s lack of clinical development experience; Enanta’s need to attract and retain senior management and key research and development personnel; Enanta’s need to obtain and maintain patent protection for its product candidates and avoid potential infringement of the intellectual property rights of others; and other risk factors described or referred to in “Risk Factors” in Enanta’s Form 10-K for the fiscal year ended
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