leritrelvir (RAY1216) / Guangdong Zhongsheng Pharma - LARVOL DELTA

Pharmacokinetic and mass balance characterization of [14C] RAY1216, a SARS-CoV-2 Mpro inhibitor, in healthy Chinese male subjects. (PubMed, Antivir Ther) - "The overall safety profile is favourable, and it demonstrates promising potential in mitigating both the duration and severity of COVID-19, and the comprehensive clinical safety and therapeutic effect are significantly superior to those of similar COVID-19 treatment drugs. RAY1216 can be referred to and further verified for the Phase II and Phase III clinical trials for the treatment of COVID-19."

Journal • PK/PD data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Single- and multiple-dose pharmacokinetics and safety of the SARS-CoV-2 3CL protease inhibitor RAY1216: a phase 1 study in healthy participants. (PubMed, Antimicrob Agents Chemother) - P1 | "Ritonavir significantly inhibited drug metabolism, and increased drug exposure increased the associated safety risks. RAY1216 was found to be well tolerated and safe in healthy participants. On the basis of preclinical results, PK characteristics, and the safety profile of RAY1216, a dosage of 400 mg three times daily was selected, thereby establishing a foundation for future research and for the clinical application of RAY1216.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT05829551."

Journal • P1 data • PK/PD data • Dyslipidemia • Hypertriglyceridemia • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Single-dose tolerability and pharmacokinetics of leritrelvir in Chinese patients with hepatic impairment and healthy matched controls. (PubMed, Antimicrob Agents Chemother) - P1 | "Overall, there was no clinically relevant difference in leritrelvir exposure in participants with hepatic impairment compared to normal controls. No dose adjustment is required for leritrelvir in patients with mild or moderate hepatic impairment.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT06161259."

Journal • PK/PD data • Hepatology • Infectious Disease • Novel Coronavirus Disease

Identification of novel small-molecule inhibitors of SARS-CoV-2 by chemical genetics. (PubMed, Acta Pharm Sin B) - "Among them, four are nucleotide analogues (remdesivir, JT001, molnupiravir, and azvudine), while the other four are protease inhibitors (nirmatrelvir, ensitrelvir, leritrelvir, and simnotrelvir-ritonavir). In vivo studies confirmed the antiviral activity of compound 172 in both Golden Syrian Hamsters and K18 humanized ACE2 mice. Overall, this study identified an alternative druggable site on the SARS-CoV-2 3CLpro, proposed a potential combination therapy with nirmatrelvir to reduce the risk of antiviral resistance and shed light on the development of allosteric protease inhibitors for treating a range of coronavirus diseases."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Model informed dose regimen optimizing in development of leritrelvir for the treatment of mild or moderate COVID-19. (PubMed, Front Pharmacol) - "This study aims to develop a pharmacokinetic model for leritrelvir, with and without ritonavir as a pharmacokinetic enhancer and to evaluate the necessity of co-administration with ritonavir and to investigate different dosage regimens. Gender and food consumption were identified as significant covariates affecting pharmacokinetic parameters, however, no dose adjustments were deemed necessary. This findings supported by subsequent phase II and phase III trials validated the appropriateness of a 400 mg TID regimen for the administration of leritrelvir."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Drug-durg Interaction of Leritrelvir(RAY1216) With Midazolam, Omeprazole, Rosuvastatin, Verapamil, and Rifampin (clinicaltrials.gov) - P1 | N=56 | Completed | Sponsor: Guangdong Raynovent Biotech Co., Ltd | Recruiting ➔ Completed

Trial completion

Mass Balance Study of [14C]RAY1216 in Healthy Adult Male Subjects in China (clinicaltrials.gov) - P1 | N=6 | Completed | Sponsor: Guangdong Raynovent Biotech Co., Ltd

New P1 trial

Preclinical evaluation of the SARS-CoV-2 Mpro inhibitor RAY1216 shows improved pharmacokinetics compared with nirmatrelvir. (PubMed, Nat Microbiol) - "It also shows improved pharmacokinetics in mice and rats, suggesting that RAY1216 could be used without ritonavir, which is co-administered with nirmatrelvir. RAY1216 has been approved as a single-component drug named 'leritrelvir' for COVID-19 treatment in China."

Journal • PK/PD data • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Pharmacokinetics of Leritrelvir(RAY1216) in Participants With Severe Kidney Disease (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Guangdong Raynovent Biotech Co., Ltd | Recruiting ➔ Completed

Trial completion • Nephrology • Renal Disease

Small-molecule antivirals treatment for COVID-19: A systematic review and network meta-analysis. (PubMed, Int J Antimicrob Agents) - "A thorough evaluation of effectiveness, applicable to both mild-to-moderate and unstratified populations, highlights the specific advantages of proxalutamide, nirmatrelvir/ritonavir, triazavirin, azvudine, molnupiravir, and VV116 in combating COVID-19. Additional clinical data are required to confirm the efficacy and safety of simnotrelvir/ritonavir and leritrelvir. The safety profiles of these antivirals were deemed acceptable."

Journal • Retrospective data • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Computer-Aided Prediction of the Interactions of Viral Proteases with Antiviral Drugs: Antiviral Potential of Broad-Spectrum Drugs. (PubMed, Molecules) - "As a result, Compounds 1-2, modified based on the structures of Ray1216 and Asunaprevir, indicate potential inhibition of DENV protease according to our computational simulation results. These studies offer ideas and insights for future research in the design of broad-spectrum antiviral drugs."

Journal • Human Immunodeficiency Virus • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

On the origins of SARS-CoV-2 main protease inhibitors. (PubMed, RSC Med Chem) - "In less than 3 years of research, 4 inhibitors of SARS-CoV-2-M have actually been authorized for COVID-19 treatment (nirmatrelvir, ensitrelvir, leritrelvir and simnotrelvir) and more such as EDP-235, FB-2001 and STI-1558/Olgotrelvir or five undisclosed compounds (CDI-988, ASC11, ALG-097558, QLS1128 and H-10517) are undergoing clinical trials. Since many series of covalent SARS-CoV-2-M inhibitors owe some of their origins to previous work on other proteases, we first provided a description of various inhibitors of cysteine-bearing human caspase-1 or cathepsin K, as well as inhibitors of serine proteases such as human dipeptidyl peptidase-4 or the hepatitis C protein complex NS3/4A. This is then followed by a description of the results of the approaches adopted (repurposing, structure-based and high throughput screening) to discover coronavirus main protease inhibitors."

Journal • Review • Hepatitis C • Hepatology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • CASP1 • CTSK • SPECC1

Leritrelvir for the treatment of mild or moderate COVID-19 without co-administered ritonavir: a multicentre randomised, double-blind, placebo-controlled phase 3 trial. (PubMed, EClinicalMedicine) - P3 | "A preclinical study has demonstrated leritrelvir poses similar antiviral activities towards different SARS-CoV-2 variants compared with nirmatrelvir. Leritrelvir monotherapy has good efficacy for mild-to-moderate COVID-19 and without serious safety concerns. This study was funded by the National Multidisciplinary Innovation Team Project of Traditional Chinese Medicine, Guangdong Science and Technology Foundation, Guangzhou Science and Technology Planning Project and R&D Program of Guangzhou Laboratory."

Journal • P3 data • Cough • Dyslipidemia • Hypertriglyceridemia • Infectious Disease • Novel Coronavirus Disease • Otorhinolaryngology • Pain • Pneumonia • Pulmonary Disease • Respiratory Diseases

Small-molecule anti-COVID-19 drugs and a focus on China's homegrown mindeudesivir (VV116). (PubMed, Front Med) - "So far, a few small-molecule antiviral drugs, including nirmatrelvir-ritonavir (Paxlovid), remdesivir, and molnupiravir have been marketed for the treatment of COVID-19...These drugs include azvudine, simnotrelvir-ritonavir (Xiannuoxin), leritrelvir, and mindeudesivir (VV116)...In this review, we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19. These findings will expand our understanding and highlight the potential widespread application of China's homegrown anti-COVID-19 drugs."

Journal • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Pharmacokinetics of Leritrelvir(Ray1216) in Elder Participants (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Guangdong Raynovent Biotech Co., Ltd

New P1 trial

Pharmacokinetics of Leritrelvir(RAY1216) in Participants With Hepatic Impairment (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Guangdong Raynovent Biotech Co., Ltd

New P1 trial • Hepatology

Pharmacokinetics of Leritrelvir(RAY1216) in Participants With Severe Kidney Disease (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: Guangdong Raynovent Biotech Co., Ltd

New P1 trial • Nephrology • Renal Disease

Drug-durg Interaction of Leritrelvir(RAY1216) With Midazolam, Omeprazole, Rosuvastatin, Verapamil, and Rifampin (clinicaltrials.gov) - P1 | N=56 | Recruiting | Sponsor: Guangdong Raynovent Biotech Co., Ltd | Not yet recruiting ➔ Recruiting

Enrollment open

Drug-durg Interaction of Leritrelvir With Midazolam, Omeprazole, Rosuvastatin, Verapamil, and Rifampin (clinicaltrials.gov) - P1 | N=56 | Not yet recruiting | Sponsor: Guangdong Raynovent Biotech Co., Ltd

New P1 trial

Antiviral efficacy of RAY1216 monotherapy and combination therapy with ritonavir in patients with COVID-19: a phase 2, single centre, randomised, double-blind, placebo-controlled trial. (PubMed, EClinicalMedicine) - "Considering the limited clinical application of RTV, it is recommended to use RAY1216 alone to further verify its efficacy and safety. This study was sponsored by the Key Research and Development Program of China (2022YFC0868700)."

Combination therapy • Journal • Monotherapy • P2 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Study of RAY1216 Tablets Compared With Placebo in Patients With Mild to Moderate COVID-19 (clinicaltrials.gov) - P3 | N=1359 | Completed | Sponsor: Guangdong Raynovent Biotech Co., Ltd | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

The Safety, Tolerability and Pharmacokinetics Study of RAY1216 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=88 | Completed | Sponsor: Guangdong Raynovent Biotech Co., Ltd

New P1 trial • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Study of RAY1216 Tablets Compared With Placebo in Patients With Mild to Moderate COVID-19 (clinicaltrials.gov) - P3 | N=1359 | Active, not recruiting | Sponsor: Guangdong Raynovent Biotech Co., Ltd | Completed ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Study of RAY1216 Tablets Compared With Placebo in Patients With Mild to Moderate COVID-19 (clinicaltrials.gov) - P3 | N=1359 | Completed | Sponsor: Guangdong Raynovent Biotech Co., Ltd | Not yet recruiting ➔ Completed | Trial completion date: Oct 2023 ➔ Mar 2023 | Trial primary completion date: Sep 2023 ➔ Jan 2023

Trial completion • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Study of RAY1216 Tablets Compared With Placebo in Patients With Mild to Moderate COVID-19 (clinicaltrials.gov) - P3 | N=1070 | Not yet recruiting | Sponsor: Guangdong Raynovent Biotech Co., Ltd

New P3 trial • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases