Atea Pharmaceuticals, Inc. announced the achievement of two significant clinical milestones from its Hepatitis C Virus (HCV) and COVID-19 programs. The Company reported positive initial data from the first 52 patients in the lead-in cohort of its Phase 2 combination 8-week study of bemnifosbuvir and ruzasvir (RZR) for the treatment of HCV. Additionally, Atea has enrolled more than 650 patients in the monotherapy arm of its Phase 3 SUNRISE-3 trial for the treatment of COVID-19, and enrollment continues with the current wave. This enrollment milestone allows for the first interim analysis of the study by the DSMB, which is expected this March. The Phase 2 open label study of bemnifosbuvir and RZR enrolled a lead-in cohort of 60 direct acting antiviral naïve, non-cirrhotic patients across all genotypes. Patients were administered 550 mg of bemnifosbuvir in combination with 180 mg of RZR once-daily for 8 weeks. Preliminary data are being presented as available, with SVR4 data currently available from 52 of the 60 lead-in patients. Including SVR4 as a decision endpoint, is a study design that is intended to substantially shorten the anticipated timeline for the completion of the Phase 2 trial. Clinical trials of other direct acting antiviral therapy combinations have demonstrated that the SVR4 result is highly correlated with SVR12.
The initial results for the first 52 patients who reached this timepoint demonstrated a SVR4 rate of 98%, including one patient with poor adherence who did not achieve SVR4. Additionally, very rapid kinetics were observed in all 60 patients across genotypes with viral load near or below the lower limit of quantification (LLOQ) at 4 weeks of treatment, which is supportive of an 8-week treatment regimen for the combination of bemnifosbuvir and RZR. All 60 patients achieved viral load below the LLOQ at the end of the treatment. The combination was generally safe and well tolerated. There were no drug related serious adverse events, no treatment discontinuations and adverse events were mostly mild.
The Phase 2 study aims to assess the safety and efficacy of 8 weeks of treatment with the combination of bemnifosbuvir and RZR in treatment-naïve HCV-infected patients, either without cirrhosis and or with compensated cirrhosis. The primary endpoint of the study is SVR12.
Approximately 280 treatment-naïve HCV-infected patients, including the lead-in cohort, are expected to be enrolled in the Phase 2 study. The second part of the trial is anticipated to enroll 220 patients across all genotypes. An expanded geographic footprint to include approximately 50 clinical sites in approximately 15 countries is currently being activated. Full enrollment of the study is expected to be completed by mid-2024 with topline results in the third quarter of 2024. Phase 3 SUNRISE-3 Trial Enrollment Update: SUNRISE-3 is a global, multicenter, randomized, double-blind, placebo-controlled, registrational Phase 3 trial evaluating bemnifosbuvir or placebo administered concurrently with locally available standard of care (SOC). The study has a large global footprint targeting approximately 300 clinical trial sites in the U.S., Europe, Japan and rest of the world. Patients are randomized 1:1 to receive either bemnifosbuvir 550 mg twice-daily (BID) or placebo BID for five days. SUNRISE-3 is the only Phase 3 program in high-risk COVID-19 patients with hospitalization as a primary endpoint.
This trial is comprised of two study populations based on the type of SOC received: 1) bemnifosbuvir as monotherapy (primary analysis), and 2) the ?combination antiviral population,? assessing combination therapy if the SOC includes other compatible antiviral drugs against COVID-19 (secondary analysis).
The SUNRISE-3 patient population includes those aged =70 years (regardless of other risk factors), individuals aged =55 years with one or more risk factors, those aged =50 years with two or more risk factors, and individuals aged =18 years with specific risk factors, including immunocompromised conditions, all irrespective of COVID-19 vaccination status.
The primary endpoint of the trial is all-cause hospitalization or death through Day 29 post-treatment in the monotherapy arm in 2,200 patients. The trial includes two interim analyses by the DSMB to assess safety and futility, to be conducted after approximately 650 and 1,350 evaluable patients, respectively, after completion of Day 29 post treatment in the monotherapy arm. Bemnifosbuvir, a nucleotide polymerase inhibitor, has been shown to be approximately 10-fold more active than sofosbuvir (SOF) in vitro against a panel of laboratory strains and clinical isolates of HCV genotypes 1?5. In vitro studies demonstrated bemnifosbuvir remained fully active against SOF resistance-associated strains (S282T), with up to 58-fold more potency than SOF. The pharmacokinetic (PK) profile of bemnifosbuvir supports once-daily dosing for the treatment of HCV and bemnifosbuvir has been well-tolerated at doses up to 550 mg for durations up to 8-12 weeks in healthy and HCV-infected subjects.
RZR, an oral NS5A inhibitor, has demonstrated highly potent and pan-genotypic antiviral activity in preclinical (picomolar range) and prior clinical studies. RZR has been administered to over 1,200 HCV-infected patients at daily doses of up to 180 mg for 12 weeks and has demonstrated a favorable safety profile. RZR?s PK profile supports once-daily dosing. Bemnifosbuvir targets the SARS-CoV-2 RNA polymerase (nsp12), a highly conserved gene which is responsible for both replication and transcription of SARS-CoV-2. Bemnifosbuvir has a unique mechanism of action, with dual targets consisting of chain termination (RdRp) and nucleotityltransferase (NiRAN) inhibition, which has the potential to create a high barrier to resistance. In vitro data confirmed that bemnifosbuvir is active with similar efficacy against all variants of concern and variants of interest that have been tested, including Omicron subvariants BA.4, BA.5, XBB and EG.5.1.