Therapy Areas: Respiratory
Enanta Pharmaceuticals Touts Positive Data from a Phase 1 Clinical Study of EDP-235, its Oral 3CL Protease Inhibitor Designed for the Treatment of COVID-19
29 July 2022 - - US-based clinical-stage biotechnology company Enanta Pharmaceuticals, Inc. (NASDAQ: ENTA) has released positive topline data from a Phase 1 study assessing the safety, tolerability, and pharmacokinetics of orally administered single ascending doses and multiple ascending doses of EDP-235 in healthy adult subjects.

EDP-235, a coronavirus 3CL protease inhibitor, which received Fast Track designation from the US Food and Drug Administration, is specifically designed to be a once-daily, oral antiviral treatment for COVID-19.

Data from the Phase 1 study demonstrated favorable safety, tolerability, and PK with strong exposure multiples over the EC90, thereby supporting the advancement of EDP-235 into a Phase 2 study using once-daily dosing, without ritonavir.

This first-in-human, randomized, double-blind, placebo-controlled Phase 1 study enrolled healthy volunteers to evaluate the safety, tolerability, and PK of oral EDP-235 in SAD and MAD for seven days, and the effect of food.

All SAD and MAD cohorts enrolled eight participants who were randomized to receive EDP-235 or placebo in a 3: 1 ratio.

To optimize dose selections, the study evaluated a broad range of single and multiples doses in fasted and fed states.

The SAD phase included five cohorts (50mg to 800mg, fasted and/or fed) and the MAD phase included four cohorts (200mg to 800mg, fasted and/or fed).

A total of 72 subjects (n=40 in SAD; n=32 in MAD) received at least one dose of EDP-235 or placebo. Overall, EDP-235 was generally safe and well-tolerated in healthy subjects up to 400mg for up to seven days.

The majority of adverse events were mild, with headache and gastrointestinal related symptoms (e.g. nausea, abdominal discomfort) being the most frequently reported AEs during the MAD phase.

There were three study discontinuations: one moderate headache in the 400mg fasted cohort, one severe headache in the 800mg fed cohort and one grade 3 ALT/grade 2 AST elevation in the 800mg fed cohort.

EDP-235 exposure increased approximately proportionally with increasing single and multiple doses, with a consistent half-life ranging from 13 to 22 hours, resulting in a PK profile suitable for once-daily dosing.

Exposure was enhanced with food administration of a standard meal.

EDP-235, Enanta's lead 3CL protease inhibitor, which has Fast Track designation, is being developed for the treatment of COVID-19.

Preclinical data show that EDP-235 potently blocks the replication of SARS-CoV-2 in multiple cellular models.

For example, in Vero cells an EC90 of 11 and 6.2 nanomolar was observed for the Alpha and Delta variant, respectively, positioning EDP-235 among the most potent direct-acting antivirals currently in development for SARS-CoV-2 infection.

Preclinical studies also show that EDP-235 has favourable distribution into lung cells as well as other key target tissues.

In addition to SARS-CoV-2, EDP-235 has potent antiviral activity against other human coronaviruses, enabling the potential for a pan-coronavirus treatment, including possibly coronaviruses that may infect human populations in the future.

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 and liver diseases.

Enanta's research and development programs include clinical candidates currently in development for the following disease targets: respiratory syncytial virus, SARS-CoV-2 (COVID-19) and hepatitis B virus.

Enanta is also conducting research in human metapneumovirus.

Enanta's research and development activities are funded by royalties from hepatitis C virus 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 and MAVIRET (ex-US) (glecaprevir/pibrentasvir).