bemnifosbuvir (AT-527) / Atea Pharma - LARVOL DELTA

Drug-drug Interaction Study of Bemnifosbuvir/Ruzasvir (BEM/RZR) and Digoxin and Rosuvastatin (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Atea Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open

No DDI between Bemnifosbuvir/Ruzasvir and Bictegravir/Emtricitabine/Tenofovir Alafenamide (EASL 2025) - "BEM/RZR and B/FTC/TAF, alone and co-administered, were well tolerated in healthy subjects with no clinically relevant PK DDI. These results support the enrollment of HCV/HIV-co- infected subjects receiving B/FTC/TAF in BEM/RZR clinical trials."

Human Immunodeficiency Virus • Infectious Disease

Pharmacokinetics of bemnifosbuvir in participants with hepatic impairment (EASL 2025) - P1 | "Background and Aims: Bemnifosbuvir (BEM, AT-527) is an oral double prodrug of a guanosine nucleotide analog with potent activity against coronaviruses and flaviviruses including hepatitis C virus (HCV). BEM in combination with ruzasvir (HCV NS5A inhibitor), is under clinical development for the treatment of chronic HCV infection... BEM 550 mg was safe and well-tolerated in participants with impaired or normal hepatic function. Plasma exposures to the parent BEM, but not the metabolite AT-273, surrogate for the active triphosphate, increased as hepatic function worsened. These results provide PK support for dosing BEM 550 mg in HCV-infected participants with compensated or decompensated cirrhosis."

PK/PD data • Fibrosis • Hepatitis C • Hepatology • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease

Efficacy and safety of Bemnifosbuvir and Ruzasvir after 8 weeks of treatment in patients with chronic hepatitis C virus (HCV) infection (EASL 2025) - P2 | "In this population with NS5A RAS high prevalence at baseline, high efficacy was observed, regardless of treatment adherence. These data support that non-cirrhotic patients can effectively be treated for 8 weeks with BEM+RZR, while cirrhotic patients will require 12 weeks of dosing to maximize efficacy. The regimen was well tolerated with no drug-related SAEs or treatment discontinuations due to AEs."

Clinical • Fibrosis • Hepatitis C • Hepatology • Infectious Disease • Inflammation • Liver Cirrhosis

Efficacy and safety of Bemnifosbuvir and Ruzasvir after 8 weeks of treatment in patients with chronic hepatitis C virus (HCV) infection (EASL 2025) - No abstract available

Clinical • Hepatitis C • Hepatology • Infectious Disease • Inflammation

Pharmacokinetics of bemnifosbuvir in participants with renal impairment (EASL 2025) - P1 | "BEM in combination with ruzasvir (HCV NS5A inhibitor), is under clinical development for the treatment of HCV... BEM 550 mg was safe and well-tolerated in participants with impaired or normal renal function. Plasma exposure to BEM was not affected by RI but increased with worsening renal function especially for the inactive nucleoside metabolite AT-273. The high renal clearance of AT-273 which exceeded GFR indicated the involvement of active transport in its renal elimination."

PK/PD data • Chronic Kidney Disease • Hepatitis C • Hepatology • Infectious Disease • Inflammation • Nephrology • Novel Coronavirus Disease • Renal Disease

Clinical Evaluation of Potential Interaction Between Bemnifosbuvir and Ruzasvir With an Assessment of Food Effect: Results of a Phase 1 Study in Healthy Participants. (PubMed, Clin Pharmacol Drug Dev) - "No serious adverse events or premature drug discontinuations were reported. Overall, the study results support further evaluation of bemnifosbuvir and ruzasvir combination therapy for treating chronic HCV."

Journal • P1 data • Hepatitis C • Hepatology • Infectious Disease • Inflammation

Drug-drug Interaction Study of Bemnifosbuvir/Ruzasvir (BEM/RZR) and Digoxin and Rosuvastatin (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: Atea Pharmaceuticals, Inc.

New P1 trial

Study of Bemnifosbuvir/Ruzasvir as a Fixed-dose Combination in Subjects With Normal or Severely Impaired Renal or Hepatic Function (clinicaltrials.gov) - P1 | N=28 | Not yet recruiting | Sponsor: Atea Pharmaceuticals, Inc.

New P1 trial • Hepatology • Renal Disease

C-BEYOND: Efficacy and Safety of BEM/RZR vs. SOF/VEL in Subjects With Chronic HCV (clinicaltrials.gov) - P3 | N=800 | Recruiting | Sponsor: Atea Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatitis C • Hepatology • Infectious Disease • Inflammation

Bemnifosbuvir and Remdesivir exhibit potent antiviral activity against tick-borne encephalitis virus in vitro (ESCMID Global 2025) - No abstract available

Preclinical • CNS Disorders

Atea Pharmaceuticals Announces Presentation of Bemnifosbuvir Preclinical Data at the 38th International Conference on Antiviral Research (ICAR) 2025 (GlobeNewswire) - "The activation of BEM is mediated by cellular enzymes including CatA/CES1, HINT1, ADALP1, GUK1, and NDPK to yield the intracellular active triphosphate metabolite AT-9010. In this preclinical study, the metabolism of BEM to its active triphosphate was demonstrated to be cell-line dependent, indicating that cell model selection is critical when evaluating in vitro efficacy of antiviral prodrugs such as BEM...Atea is initiating a global Phase 3 program and expects patient enrollment to start in April 2025."

Preclinical • Trial status • Hepatitis C

C-BEYOND: Efficacy and Safety of BEM/RZR Vs. SOF/VEL in Subjects with Chronic HCV (clinicaltrials.gov) - P3 | N=800 | Not yet recruiting | Sponsor: Atea Pharmaceuticals, Inc.

New P3 trial • Hepatitis C • Hepatology • Infectious Disease • Inflammation

Bemnifosbuvir and ruzasvir in combination exhibit potent synergistic antiviral activity in vitro while maintaining a favorable nonclinical safety profile in vivo. (PubMed, Antiviral Res) - "All doses were well tolerated with no test article-related adverse effects identified in either the separate or combined dose groups. Moreover, toxicokinetic analyses conducted on dose days 1, 28 and 84 indicated minimal pharmacokinetic interactions between the two drugs in rats, with AUC values for AT-511 (free base form of BEM), its major circulating metabolites, and RZR being similar, regardless of separate or co-administration."

Journal • Preclinical

A Phase 2, Safety and Efficacy of Bemnifosbuvir (BEM) and Ruzasvir (RZR) in Subjects with Chronic HCV (clinicaltrials.gov) - P2 | N=275 | Completed | Sponsor: Atea Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed

Trial completion • Fibrosis • Hepatitis C • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis

MULTISCALE MODELING OF LEAD-IN RESULTS FROM A PHASE 2 STUDY OF AN 8-WEEK COMBINATION REGIMEN OF BEMNIFOSBUVIR AND RUZASVIR IN PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION (AASLD 2024) - P2 | "Previously we developed a multiscale model of HCV infection and treatment to estimate the in vivo effectiveness of daclatasvir in blocking HCV replication and viral assembly/secretion... BEM/ RZR for 8 weeks was highly effective in blocking both viral replication and viral assembly/secretion in HCV-infected patients independent of genotype, age, sex or fibrosis stage. This analysis supports the shortened 8 weeks of treatment with BEM/RZR for CHC."

Clinical • P2 data • Fibrosis • Hepatitis C • Hepatology • Immunology • Infectious Disease • Inflammation

BEMNIFOSBUVIR POSES HIGH BARRIER FOR RESISTANCE IN BOTH PRECLINICAL AND PHASE 1B MONOTHERAPY STUDIES (AASLD 2024) - P1, P2 | "BEM has demonstrated a strong capacity to inhibit HCV replication in vitro and in vivo, without the rapid development of viral resistance. Given the highly potent pan-genotypic antiviral activity and high resistance barrier of BEM, it is currently being developed in combination with ruzasvir (RZR), a picomolar potent pan-genotypic NS5A inhibitor, for the treatment of HCV infections in a Phase 2 clinical trial (NCT05904470). The combination of BEM/RZR should have a more compelling antiviral profile against all genotypes than current SOCs."

Monotherapy • P1 data • Preclinical • Hepatitis C • Infectious Disease

BEMNIFOSBUVIR DOES NOT ALTER CARDIAC REPOLARIZATION IN HEALTHY PARTICIPANTS: RESULTS FROM A THOROUGH QT STUDY (AASLD 2024) - "Background: Bemnifosbuvir (BEM, AT-527) is an oral double prodrug of a guanosine nucleotide analog with potent activities against coronaviruses and flaviviruses including hepatitis C virus and SARS-CoV-2 and is under clinical development for the treatment of COVID-19 (phase 3) and chronic hepatitis C (phase 2)... BEM had no clinically relevant effects on cardiac repolarization, heart rate, PR interval, or QRS duration. An QTc effect exceeding 10 ms, the established threshold of concern, can be excluded across the observed plasma concentration ranges of BEM and its metabolites expected to exceed high clinical exposure scenarios."

Clinical • Hepatitis C • Hepatology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases

Pharmacokinetics of Fixed-Dose Combination Tablet of Bemnifosbuvir and Ruzasvir (clinicaltrials.gov) - P1 | N=42 | Completed | Sponsor: Atea Pharmaceuticals, Inc. | Recruiting ➔ Completed | N=20 ➔ 42

Enrollment change • Trial completion

Proximal fleximer analogues of 2'-deoxy-2'-fluoro-2'-methyl purine nucleos(t)ides: Synthesis and preliminary pharmacokinetic and antiviral evaluation. (PubMed, Bioorg Med Chem) - "Neither compound exhibited activity for any of the other viruses tested. The parent flex-nucleoside analogue was screened for toxicity in CD-1 mice and showed no adverse effects up to 300 mg/kg, the maximum concentration tested."

Journal • PK/PD data • Ebola Virus Disease • Infectious Disease • Novel Coronavirus Disease

The activation cascade of the broad-spectrum antiviral bemnifosbuvir characterized at atomic resolution. (PubMed, PLoS Biol) - "Bemnifosbuvir (AT-527) and AT-752 are guanosine analogues currently in clinical trials against several RNA viruses. Crystal structures of human histidine triad nucleotide binding protein 1, adenosine deaminase-like protein 1, guanylate kinase 1, and nucleoside diphosphate kinase at 2.09, 2.44, 1.76, and 1.9 Å resolution, respectively, with cognate precursors of AT-9010 illuminate the activation pathway from the orally available bemnifosbuvir to AT-9010, pointing to key drug-protein contacts along the activation pathway. Our work provides a framework to integrate the design of antiviral nucleotide analogues, confronting requirements and constraints associated with activation enzymes along the 5'-triphosphate assembly line."

Journal • HINT1

SUNRISE-3: Efficacy and Safety of Bemnifosbuvir in High-Risk Outpatients With COVID-19 (clinicaltrials.gov) - P3 | N=2295 | Completed | Sponsor: Atea Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CD4

Study of Bemnifosbuvir in Subjects With Normal and Impaired Hepatic Function (clinicaltrials.gov) - P1 | N=39 | Completed | Sponsor: Atea Pharmaceuticals, Inc. | Recruiting ➔ Completed

Trial completion • Hepatology

Pharmacokinetics of Fixed-Dose Combination Tablet of Bemnifosbuvir and Ruzasvir (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Atea Pharmaceuticals, Inc. | Trial completion date: Feb 2024 ➔ Aug 2024 | Trial primary completion date: Feb 2024 ➔ Aug 2024

Trial completion date • Trial primary completion date

Study of AT-527 in Subjects With Normal and Impaired Renal Function (clinicaltrials.gov) - P1 | N=36 | Completed | Sponsor: Atea Pharmaceuticals, Inc. | Recruiting ➔ Completed

Trial completion • Renal Disease