Simnotrelvir as a potential treatment for COVID-19

ABSTRACT

Introduction

Simnotrelvir is a selective 3-chymotrypsin-like oral protease inhibitor with activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Areas Covered

On 18 January 2024, results of a double-blind, randomized, placebo-controlled trial of simnotrelvir as a treatment for mild-to moderate COVID-19-were published, indicating the drug, when given in combination with ritonavir, shortened the time to resolution of symptoms.

Expert Opinion

Treatment options for most outpatients with mild-to-moderate COVID-19 are limited. The protease inhibitor nirmatrelvir in combination with ritonavir has proven effective in patients who are high risk for progression to severe COVID-19, but there are no approved therapies for standard-risk patients, who now comprise the majority of the population. Simnotrelvir appears to be effective in standard-risk patients, including those who have completed primary vaccination against COVID-19 and have received a booster dose. This manuscript examines the rationale for the development of simnotrelvir and explores how this drug may be used in the future to treat COVID-19.

KEYWORDS:

• Simnotrelvir
• paxlovid
• nirmatrelvir
• ritonavir
• SARS-CoV-2
• COVID-19

Article highlights

• There are limited treatment options for adults with SARS-CoV-2 infection who are at standard risk for progression to severe COVID-19.

• Paxlovid (nirmatrelvir/ritonavir) is the preferred therapy for high-risk outpatients, but this treatment has been associated with both viral and symptomatic rebound as well as drug-drug interactions.

• Simnotrelvir is an oral 3-chymotrypsin-like protease inhibitor that has in vitro activity against SARS-CoV-2 that has shown promise in both pre-clinical and clinical studies.

• A double-blind, placebo-controlled phase 2-3 study of adults with mild-to-moderate COVID-19 found that simnotrelvir/ritonavir shortened the time to sustained resolution of symptoms compared to treatment with placebo.

• Head-to-head studies of the most promising new drug candidates, including simnotrelvir, ensitrelvir, and mindeudesivir are urgently needed to establish the preferred therapy for standard risk adults with COVID-19.

Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.