Effect of Bamlanivimab as Monotherapy or in Combination With Etesevimab on Viral Load in Patients With Mild to Moderate COVID-19
et al., JAMA, doi:10.1001/jama.2021.0202, Jan 2021
25th treatment shown to reduce risk in
May 2021, now with p = 0.00049 from 22 studies, recognized in 11 countries.
Efficacy is variant dependent.
No treatment is 100% effective. Protocols
combine treatments.
6,300+ studies for
210+ treatments. c19early.org
|
RCT for LY-CoV555 monotherapy and LY-CoV555/LY-CoV016 combination therapy with 592 patients showing lower hospitalization/ER visits with treatment.
For viral load at day 11, a statistically significant reduction was found with combination therapy but not monotherapy.
Standard of Care (SOC) for COVID-19 in the study country,
the USA, is very poor with very low average efficacy for approved treatments6.
Only expensive, high-profit treatments were approved for early treatment. Low-cost treatments were excluded, reducing the probability of early treatment due to access and cost barriers, and eliminating complementary and synergistic benefits seen with many low-cost treatments.
|
risk of hospitalization/ER, 70.6% lower, RR 0.29, p = 0.046, treatment 4 of 101 (4.0%), control 7 of 52 (13.5%), NNT 11, LY-CoV555 all dosages.
|
|
risk of hospitalization/ER, 79.9% lower, RR 0.20, p = 0.13, treatment 1 of 37 (2.7%), control 7 of 52 (13.5%), NNT 9.3, LY-CoV555 700mg.
|
|
risk of hospitalization/ER, 75.2% lower, RR 0.25, p = 0.25, treatment 1 of 30 (3.3%), control 7 of 52 (13.5%), NNT 9.9, LY-CoV555 2800mg.
|
|
risk of hospitalization/ER, 56.3% lower, RR 0.44, p = 0.31, treatment 2 of 34 (5.9%), control 7 of 52 (13.5%), NNT 13, LY-CoV555 7000mg.
|
|
risk of hospitalization/ER, 91.8% lower, RR 0.08, p = 0.04, treatment 0 of 31 (0.0%), control 7 of 52 (13.5%), NNT 7.4, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), LY-CoV555/LY-CoV016.
|
| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
1.
Liu et al., Striking Antibody Evasion Manifested by the Omicron Variant of SARS-CoV-2, bioRxiv, doi:10.1101/2021.12.14.472719.
2.
Sheward et al., Variable loss of antibody potency against SARS-CoV-2 B.1.1.529 (Omicron), bioRxiv, doi:10.1101/2021.12.19.473354.
3.
VanBlargan et al., An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by several therapeutic monoclonal antibodies, bioRxiv, doi:10.1101/2021.12.15.472828.
4.
Pochtovyi et al., In Vitro Efficacy of Antivirals and Monoclonal Antibodies against SARS-CoV-2 Omicron Lineages XBB.1.9.1, XBB.1.9.3, XBB.1.5, XBB.1.16, XBB.2.4, BQ.1.1.45, CH.1.1, and CL.1, Vaccines, doi:10.3390/vaccines11101533.
Gottlieb et al., 21 Jan 2021, Randomized Controlled Trial, USA, peer-reviewed, 27 authors, study period 17 June, 2020 - 6 October, 2020, average treatment delay 4.0 days.
Effect of Bamlanivimab as Monotherapy or in Combination With Etesevimab on Viral Load in Patients With Mild to Moderate COVID-19
JAMA, doi:10.1001/jama.2021.0202
IMPORTANCE Coronavirus disease 2019 (COVID-19) continues to spread rapidly worldwide. Neutralizing antibodies are a potential treatment for COVID-19. OBJECTIVE To determine the effect of bamlanivimab monotherapy and combination therapy with bamlanivimab and etesevimab on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in mild to moderate COVID-19.
DESIGN, SETTING, AND PARTICIPANTS The BLAZE-1 study is a randomized phase 2/3 trial at 49 US centers including ambulatory patients (N = 613) who tested positive for SARS-CoV-2 infection and had 1 or more mild to moderate symptoms. Patients who received bamlanivimab monotherapy or placebo were enrolled first (June 17-August 21, 2020) followed by patients who received bamlanivimab and etesevimab or placebo (August 22-September 3). These are the final analyses and represent findings through October 6, 2020. INTERVENTIONS Patients were randomized to receive a single infusion of bamlanivimab (700 mg [n = 101], 2800 mg [n = 107], or 7000 mg [n = 101]), the combination treatment (2800 mg of bamlanivimab and 2800 mg of etesevimab [n = 112]), or placebo (n = 156). MAIN OUTCOMES AND MEASURES The primary end point was change in SARS-CoV-2 log viral load at day 11 (±4 days). Nine prespecified secondary outcome measures were evaluated with comparisons between each treatment group and placebo, and included 3 other measures of viral load, 5 on symptoms, and 1 measure of clinical outcome (the proportion of patients with a COVID-19-related hospitalization, an emergency department [ED] visit, or death at day 29). RESULTS Among the 577 patients who were randomized and received an infusion (mean age, 44.7 [SD, 15.7] years; 315 [54.6%] women), 533 (92.4%) completed the efficacy evaluation period (day 29). The change in log viral load from baseline at day 11 was -3.72 for 700 mg, -4.08 for 2800 mg, -3.49for7000mg,-4.37forcombinationtreatment,and-3.80forplacebo.Comparedwithplacebo, the differences in the change in log viral load at day 11 were 0.09 (95% CI, -0.35 to 0.52; P = .69)for 700 mg, -0.27 (95% CI, -0.71 to 0.16; P = .21) for 2800 mg, 0.31 (95% CI, -0.13 to 0.76; P = .16) for 7000 mg, and -0.57 (95% CI, -1.00 to -0.14; P = .01) for combination treatment. Among the secondary outcome measures, differences between each treatment group vs the placebo group werestatisticallysignificantfor10of84endpoints.TheproportionofpatientswithCOVID-19-related hospitalizationsorEDvisitswas5.8%(9events)forplacebo,1.0%(1event)for700mg,1.9%(2events) for 2800 mg, 2.0% (2 events) for 7000 mg, and 0.9% (1 event) for combination treatment. Immediate hypersensitivity reactions were reported in 9 patients (6 bamlanivimab, 2 combination treatment, and 1 placebo). No deaths occurred during the study treatment. CONCLUSIONS AND RELEVANCE Among nonhospitalized patients with mild to moderate COVID-19 illness, treatment with bamlanivimab and etesevimab, compared with placebo, was associated with a statistically significant..
References
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