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All Studies   Meta Analysis    Recent:   
0 0.5 1 1.5 2+ Mortality 86% Improvement Relative Risk Progression 27% Recovery 2% Viral clearance 9% Bemnifosbuvir  Horga et al.  LATE TREATMENT  DB RCT Is late treatment with bemnifosbuvir beneficial for COVID-19? Double-blind RCT 83 patients in the USA Lower mortality with bemnifosbuvir (not stat. sig., p=0.24) c19early.org Horga et al., Future Virology, June 2023 Favors bemnifosbuvir Favors control

Phase II study of bemnifosbuvir in high-risk participants in a hospital setting with moderate COVID-19

Horga et al., Future Virology, doi:10.2217/fvl-2023-0064, NCT04396106
Jun 2023  
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Phase 2 RCT investigating bemnifosbuvir for the treatment of 81 high-risk COVID-19 patients hospitalized with moderate disease. The trial was terminated early due to difficulties with enrollment. There was no significant difference between bemnifosbuvir and placebo for the primary outcome of disease progression or most secondary outcomes. However, viral load declined faster in the bemnifosbuvir group between days 2 and 8. All 3 deaths occurred in the placebo group. The safety profile was similar between groups. While results are very limited by small sample size and early termination, they suggest bemnifosbuvir may accelerate viral clearance and could play a role in preventing progression.
Viral load measured by PCR may not accurately reflect infectious virus measured by viral culture. Porter show that viral load early in infection was correlated with infectious virus, but viral load late in infection could be high even with low or undetectable infectious virus. Assessing viral load later in infection may underestimate reductions in infectious virus with treatment.
risk of death, 85.6% lower, RR 0.14, p = 0.24, treatment 0 of 41 (0.0%), control 3 of 42 (7.1%), NNT 14, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
risk of progression, 26.8% lower, RR 0.73, p = 0.71, treatment 3 of 41 (7.3%), control 4 of 40 (10.0%), NNT 37, PRI.
risk of no recovery, 2.4% lower, RR 0.98, p = 1.00, treatment 8 of 41 (19.5%), control 8 of 40 (20.0%), NNT 205, clinical recovery.
risk of no viral clearance, 9.4% lower, RR 0.91, p = 0.80, treatment 13 of 27 (48.1%), control 17 of 32 (53.1%), NNT 20, day 14.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Horga et al., 23 Jun 2023, Double Blind Randomized Controlled Trial, placebo-controlled, USA, peer-reviewed, 8 authors, trial NCT04396106 (history). Contact: reprints@futuremedicine.com, horga.arantxa@ateapharma.com.
This PaperBemnifosbuvirAll
Phase II study of bemnifosbuvir in high-risk participants in a hospital setting with moderate COVID-19
Arantxa Horga, Daniel R Kuritzkes, John J Kowalczyk, Keith Pietropaolo, Bruce Belanger, Kai Lin, Kristen Perkins, Janet Hammond
Future Virology, doi:10.2217/fvl-2023-0064
Background: Bemnifosbuvir, a novel, oral, nonmutagenic, nonteratogenic nucleotide analogue inhibits SARS-CoV-2 replication in vitro. Materials & methods: Adults in hospital settings with moderate COVID-19 were randomized 1:1 bemnifosbuvir/placebo. Study amended to two parts after interim analysis; part B enrollment limited owing to evolving standard of care. Results: Although the study ended early and did not meet the primary efficacy end point, bemnifosbuvir was well tolerated and did not contribute to allcause mortality. Compared with placebo, bemnifosbuvir treatment resulted in 0.61 log 10 greater viral load mean change on day 2; trend sustained through day 8. Treatment-emergent adverse events were similar in both groups; most were mild/moderate, unrelated to study drug. Conclusion: Our results suggest a potential role for bemnifosbuvir in blunting COVID-19 progression. Clinical Trial Registration: NCT04396106 (ClinicalTrials.gov) Tweetable abstract: #Bemnifosbuvir, a novel/oral/nonmutagenic/nonteratogenic/nucleotide analogue with low DDI/resistance potential, inhibits SARS-CoV-2 replication and was well tolerated, did not contribute to all cause mortality and resulted in greater viral load mean change. Results suggest potential to blunt #COVID-19 progression.
Supplementary data To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/ suppl/10.2217/fvl-2023-0064 Author contributions All authors were involved in the development of the study protocols; in the collection, analysis and interpretation of study data; in writing of the clinical study report; and in the decision to submit the article for publication. Ethical conduct of research The authors state that they have obtained appropriate institutional review board approval and have followed the principles outlined in the Declaration of Helsinki for all human experimental investigations. In addition, informed consent has been obtained from the participants involved.
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Late treatment
is less effective
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