Casirivimab/imdevimab for COVID-19: real-time analysis of all 23 studies

Casirivimab/imdevimab for COVID-19: real-time meta analysis of 15 studies

Covid Analysis (Preprint) (meta analysis)

• Statistically significant improvements are seen for mortality, hospitalization, progression, recovery, cases, and viral clearance. 13 studies from 8 independent teams in 3 different countries show statistically significant improvements in isolation (6 for the most serious outcome).

• Meta analysis using the most serious outcome reported shows 66% [45‑80%] improvement. Results are similar for Randomized Controlled Trials, similar after exclusions, and better for peer-reviewed studies. Early treatment is more effective than late treatment.

• Results are robust — in exclusion sensitivity analysis 10 of 15 studies must be excluded to avoid finding statistically significant efficacy in pooled analysis.

• Efficacy is variant dependent. In Vitro studies suggest a lack of efficacy for omicron [Liu, Sheward, VanBlargan]. Monoclonal antibody use with variants can be associated with prolonged viral loads, clinical deterioration, and immune escape [Choudhary].

• While many treatments have some level of efficacy, they do not replace vaccines and other measures to avoid infection. Only 33% of casirivimab/imdevimab studies show zero events in the treatment arm.

• Multiple treatments are typically used in combination, and other treatments may be more effective.

• Elimination of COVID-19 is a race against viral evolution. No treatment, vaccine, or intervention is 100% available and effective for all variants. All practical, effective, and safe means should be used, including treatments, as supported by Pfizer [Pfizer]. Denying the efficacy of treatments increases mortality, morbidity, collateral damage, and endemic risk.

• All data to reproduce this paper and sources are in the appendix.

	Studies	Early treatment	Late treatment	Prophylaxis	Patients	Authors
All studies	15	63% [43‑76%]	33% [-17‑61%]	93% [79‑97%]	39,275	296
With exclusions	14	62% [39‑76%]	33% [-17‑61%]	93% [79‑97%]	29,593	287
Peer-reviewed	5	80% [43‑93%]			19,845	104
RCTs	9	62% [39‑76%]	19% [-17‑44%]	93% [79‑97%]	21,306	177
Percentage improvement with casirivimab/imdevimab treatment

Covid Analysis et al., 1/22/2022, preprint, 1 author.

Effect of Subcutaneous Casirivimab and Imdevimab Antibody Combination vs Placebo on Development of Symptomatic COVID-19 in Early Asymptomatic SARS-CoV-2 Infection: A Randomized Clinical Trial

O'Brien et al., JAMA, doi:10.1001/jama.2021.24939768 (Peer Reviewed)

RCT 204 asymptomatic COVID+ patients, 100 treated with subcutaneous casirivimab/imdevimab, showing lower development of symptoms, lower hospitalization, and faster viral clearance with treatment. Study conducted prior to widespread circulation of delta and omicron in the study locations.

risk of hospitalization, 85.5% lower, RR 0.15, p = 0.25, treatment 0 of 100 (0.0%), control 3 of 104 (2.9%), NNT 35, relative risk is not 0 because of continuity correction due to zero events.

risk of hospitalization/ER, 92.2% lower, RR 0.08, p = 0.03, treatment 0 of 100 (0.0%), control 6 of 104 (5.8%), NNT 17, relative risk is not 0 because of continuity correction due to zero events.

risk of symptomatic case, 33.0% lower, RR 0.67, p = 0.04, treatment 29 of 100 (29.0%), control 44 of 104 (42.3%), NNT 7.5, OR converted to RR, day 14.

relative weeks with high viral load, 39.7% better, RR 0.60, p = 0.001, treatment 100, control 104.

O'Brien et al., 1/14/2022, Double Blind Randomized Controlled Trial, placebo-controlled, multiple countries, multiple regions, peer-reviewed, 38 authors, study period 13 July, 2020 - 28 January, 2021.

Real-world clinical outcomes of treatment with casirivimab-imdevimab among patients with mild-to-moderate coronavirus disease 2019 during the Delta variant pandemic

Suzuki et al., medRxiv, doi:10.1101/2021.12.19.21268078 (Preprint)

Retrospective 949 patients in Japan, 314 treated with casirivimab/imdevimab showing significantly lower risk of deterioration with treatment.

risk of death, 200.0% higher, RR 3.00, p = 1.00, treatment 1 of 222 (0.5%), control 0 of 222 (0.0%), continuity correction due to zero event, propensity score matching.

risk of death, 59.6% lower, RR 0.40, p = 0.67, treatment 1 of 314 (0.3%), control 5 of 635 (0.8%), NNT 213, unadjusted.

risk of progression, 45.2% lower, RR 0.55, p = 0.02, treatment 17 of 222 (7.7%), control 31 of 222 (14.0%), NNT 16, propensity score matching.

risk of progression, 49.9% lower, RR 0.50, p = 0.002, treatment 34 of 314 (10.8%), control 70 of 365 (19.2%), NNT 12, OR converted to RR, multivariate.

Suzuki et al., 12/21/2021, retrospective, Japan, Asia, preprint, 49 authors, study period 24 July, 2021 - 30 September, 2021.

Variable loss of antibody potency against SARS-CoV-2 B.1.1.529 (Omicron)

Sheward et al., bioRxiv, doi:10.1101/2021.12.19.473354 (Preprint) (In Vitro)

In Vitro study showing that omicron is substantially resistant to neutralization by monoclonal antibodies REGN10933, REGN10987, Ly-CoV016 and Ly-CoV555. S309 (the parent of Sotrovimab) had only 2-fold loss in potency.

Sheward et al., 12/20/2021, preprint, 11 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

The effect of casirivimab with imdevimab on disease progression in nonsevere COVID‐19 patients in a single hospital in Japan

Komagamine et al., Journal of General and Family Medicine, doi:10.1002/jgf2.516 (Peer Reviewed)

Combined retrospective/prospective study in Japan with 53 casirivimab/imdevimab patients and 75 control patients, showing significantly lower progression with treatment.

risk of mechanical ventilation, 77.3% lower, RR 0.23, p = 0.51, treatment 0 of 53 (0.0%), control 2 of 75 (2.7%), NNT 38, relative risk is not 0 because of continuity correction due to zero events.

risk of ICU admission, 92.3% lower, RR 0.08, p = 0.04, treatment 0 of 53 (0.0%), control 7 of 75 (9.3%), NNT 11, relative risk is not 0 because of continuity correction due to zero events.

risk of progression, 67.8% lower, RR 0.32, p = 0.006, treatment 8 of 53 (15.1%), control 33 of 75 (44.0%), NNT 3.5, adjusted, OR converted to RR, multivariable.

hospitalization time, 28.9% lower, relative time 0.71, p < 0.001, treatment 53, control 75.

Komagamine et al., 12/19/2021, retrospective, Japan, Asia, peer-reviewed, 4 authors, average treatment delay 5.0 days.

An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by several therapeutic monoclonal antibodies

VanBlargan et al., bioRxiv, doi:10.1101/2021.12.15.472828 (Preprint) (In Vitro)

In vitro study (Vero-TMPRSS2 and Vero-hACE2-TMPRSS2) showing complete loss of inhibitory activity for B.1.1.529 omicron with LY-CoV555, LY-CoV016, REGN10933, REGN10987, and CT-P59, ~12-fold decrease for COV2-2196/COV2-2130, and minimal change for S309.

VanBlargan et al., 12/17/2021, preprint, 10 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

Striking Antibody Evasion Manifested by the Omicron Variant of SARS-CoV-2

Liu et al., bioRxiv, doi:10.1101/2021.12.14.472719 (Preprint) (In Vitro)

In vitro study (Vero-E6-TMPRSS2) showing 18 of 19 monoclonal antibodies were no longer effective or significantly impaired with B.1.1.529 omicron.

Liu et al., 12/15/2021, preprint, 23 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

Association of subcutaneous or intravenous route of administration of casirivimab and imdevimab monoclonal antibodies with clinical outcomes in COVID-19

McCreary et al., medRxiv, doi:10.1101/2021.11.30.21266756 (Preprint)

Prospective study comparing subcutaneous and intravenous casirivimab/imdevimab, and comparing to a PSM matched control set, showing significantly lower mortality and hospitalization with treatment. Controls were matched with EUA-eligible risk factors only, authors were unable to determine symptom severity.

risk of death, 93.0% lower, RR 0.07, p = 0.009, treatment 1 of 652 (0.2%), control 29 of 1,304 (2.2%), NNT 48, propensity score matching.

risk of death/hospitalization, 56.0% lower, RR 0.44, p < 0.001, treatment 22 of 652 (3.4%), control 101 of 1,304 (7.7%), NNT 23, propensity score matching.

risk of hospitalization, 48.0% lower, RR 0.52, p = 0.005, treatment 22 of 652 (3.4%), control 85 of 1,304 (6.5%), NNT 32, propensity score matching.

risk of hospitalization/ER, 40.0% lower, RR 0.60, p = 0.003, treatment 40 of 652 (6.1%), control 133 of 1,304 (10.2%), NNT 25, propensity score matching.

SQ vs. IV death, 53.0% lower, RR 0.47, p = 0.52, treatment 1 of 969 (0.1%), control 3 of 1,216 (0.2%), NNT 697, adjusted.

SQ vs. IV death/hosp., 71.0% higher, RR 1.71, p = 0.06, treatment 27 of 969 (2.8%), control 21 of 1,216 (1.7%), adjusted.

SQ vs. IV hospitalization, 79.0% higher, RR 1.79, p = 0.046, treatment 27 of 969 (2.8%), control 20 of 1,216 (1.6%), adjusted.

SQ vs. IV ER/hosp., 15.0% lower, RR 0.85, p = 0.38, treatment 47 of 969 (4.9%), control 71 of 1,216 (5.8%), NNT 101, adjusted.

McCreary et al., 12/1/2021, prospective, USA, North America, preprint, 27 authors, study period 14 July, 2021 - 26 October, 2021, average treatment delay 6.0 days.

Repeat Subcutaneous Administration of REGEN-COV® in Adults is Well-Tolerated and Prevents the Occurrence of COVID-19

Isa et al., medRxiv, doi:10.1101/2021.11.10.21265889 (Preprint)

RCT 969 patients, 729 treated with monthly subcutaneous casirivimab/imdevimab, showing significantly lower risk of COVID-19 with treatment. There were no grade 3 injection site reactions or hypersensitivity reactions. Slightly more TEAEs were reported with treatment (54.9% vs. 48.3%), due to grade 1-2 ISRs. Serious adverse events were rare and occurred with similar percentages for treatment and control groups. There were no deaths. NCT04519437.

risk of symptomatic case, 92.6% lower, RR 0.07, p = 0.002, treatment 3 of 729 (0.4%), control 13 of 240 (5.4%), NNT 20, OR converted to RR.

risk of case, 92.7% lower, RR 0.07, p = 0.002, treatment 0 of 729 (0.0%), control 10 of 240 (4.2%), NNT 24, OR converted to RR, relative risk is not 0 because of continuity correction due to zero events, seroconversion.

Conflicts of interest: employee of the drug patent holder.

Isa et al., 11/16/2021, Double Blind Randomized Controlled Trial, USA, North America, preprint, 31 authors.

REGEN-COV for the Treatment of Hospitalized Patients with Covid-19

Somersan-Karakaya et al., medRxiv, doi:10.1101/2021.11.05.21265656 (Preprint)

RCT 1,336 hospitalized patients with symptom onset <=10 days on low-flow or no supplemental oxygen, showing lower mortality with treatment. Cohorts 2&3 were paused mid-trial due to increased deaths in the treatment arm and these results were not included. NCT04426695.

risk of death, 35.9% lower, RR 0.64, p = 0.02, treatment 59 of 804 (7.3%), control 45 of 393 (11.5%), NNT 24, day 28, mFAS.

risk of death, 55.6% lower, RR 0.44, p = 0.005, treatment 24 of 360 (6.7%), control 24 of 160 (15.0%), NNT 12, seronegative, day 28, mFAS.

risk of death, 21.3% lower, RR 0.79, p = 0.42, treatment 26 of 369 (7.0%), control 18 of 201 (9.0%), NNT 52, seropositive, day 28, mFAS.

risk of death/intubation, 30.9% lower, RR 0.69, p = 0.03, treatment 82 of 804 (10.2%), control 58 of 393 (14.8%), NNT 22, day 1-29, mFAS.

risk of no hospital discharge, 28.6% lower, RR 0.71, p = 0.03, treatment 92 of 804 (11.4%), control 63 of 393 (16.0%), NNT 22, day 1-29, mFAS.

Conflicts of interest: research funding from the drug patent holder, employee of the drug patent holder.

Somersan-Karakaya et al., 11/8/2021, Double Blind Randomized Controlled Trial, multiple countries, multiple regions, preprint, 31 authors.

New phase 3 analyses show that a single dose of REGEN-COV® (casirivimab and imdevimab) provides long-term protection against COVID-19

Regeneron Press Release (News)

Long-term results for PEP RCT NCT04452318, with 841 baseline seronegative casirivimab/imdevimab patients and 842 placebo patients, showing significantly lower cases with treatment.

risk of hospitalization, 92.3% lower, RR 0.08, p = 0.03, treatment 0 of 841 (0.0%), control 6 of 842 (0.7%), NNT 140, relative risk is not 0 because of continuity correction due to zero events, 8 months.

risk of case, 81.5% lower, RR 0.19, p < 0.001, treatment 20 of 841 (2.4%), control 108 of 842 (12.8%), NNT 9.6, months 1-8.

risk of case, 81.6% lower, RR 0.18, p < 0.001, treatment 7 of 841 (0.8%), control 38 of 842 (4.5%), NNT 27, months 2-8.

risk of hospitalization/ER, 88.9% lower, RR 0.11, p = 0.06, treatment 0 of 753 (0.0%), control 4 of 752 (0.5%), NNT 188, relative risk is not 0 because of continuity correction due to zero events, day 29.

risk of symptomatic case, 81.4% lower, RR 0.19, p < 0.001, treatment 11 of 753 (1.5%), control 59 of 752 (7.8%), NNT 16, day 29.

recovery time, 62.5% lower, relative time 0.37, p < 0.001, treatment 753, control 752, short-term followup, relative time with symptoms.

time to viral-, 69.2% lower, relative time 0.31, p < 0.001, treatment 753, control 752, short-term followup, relative time with high viral load.

Regeneron et al., 11/8/2021, Double Blind Randomized Controlled Trial, multiple countries, multiple regions, preprint, 1 author.

Impact of Antibody Cocktail Therapy Combined with Casirivimab and Imdevimab on Clinical Outcome for Covid-19 patients in A Real-Life Setting: A Single Institute Analysis

Kakinoki et al., medRxiv, doi:10.1101/2021.10.10.21264589 (Preprint)

Retrospective 55 patients in Japan treated a median of 3 days from symptom onset with casirivimab/imdevimab, and 53 control patients, showing lower risk of further treatment including oxygen or antivirals.

risk of further treatment including oxygen or antivirals, 57.6% lower, RR 0.42, p = 0.049, treatment 13 of 55 (23.6%), control 22 of 53 (41.5%), NNT 5.6, OR converted to RR, multivariate.

Kakinoki et al., 11/4/2021, retrospective, Japan, Asia, preprint, 16 authors, average treatment delay 3.0 days.

Antibody escape and global spread of SARS-CoV-2 lineage A.27

Kaleta et al., Research Square, doi:10.21203/rs.3.rs-995033/v1 (Preprint) (In Vitro)

Anaysis of antibody escape showing variant A.27 completely escaped neutralization with LY-COV555 and partially with REGN10987. B.1.617.2 escaped these antibodies in a similar manner, suggesting that L452R facilitates the escape. Authors note that B.1.351 and P.1 escaped LY-COV555 and REGN10933, likely facilitated by the E484K mutation, suggesting that L452R and E484K lead to escape from LY-COV555 and to partial resistance to either REGN10987 or REGN10933, respectively.

Kaleta et al., 11/2/2021, preprint, 33 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

Monoclonal Antibody Treatment of Breakthrough COVID-19 in Fully Vaccinated Individuals with High-Risk Comorbidities

Bierle et al., The Journal of Infectious Diseases, doi:10.1093/infdis/jiab570 (preprint 10/20/2021) (Peer Reviewed)

Retrospective 1,395 vaccinated COVID-19 cases, showing significantly lower hospitalization and oxygen supplementation with monoclonal antibody treatment, primarily casirivimab-imdevimab. Hospitalization was significantly associated with comorbidities.

risk of ICU admission, 88.9% lower, RR 0.11, p = 0.16, treatment 0 of 527 (0.0%), control 5 of 868 (0.6%), NNT 174, relative risk is not 0 because of continuity correction due to zero events.

risk of oxygen therapy, 85.3% lower, RR 0.15, p < 0.001, treatment 5 of 527 (0.9%), control 56 of 868 (6.5%), NNT 18, OR converted to RR.

risk of hospitalization, 75.3% lower, RR 0.25, p < 0.001, treatment 14 of 527 (2.7%), control 93 of 868 (10.7%), NNT 12, OR converted to RR.

Excluded in meta analysis: patients were treated with different medications, results specific to each medication were not reported. Conflicts of interest: research funding from the drug patent holder.

Bierle et al., 10/20/2021, retrospective, USA, North America, peer-reviewed, 7 authors.

Real-world Assessment of 2,879 COVID-19 Patients Treated with Monoclonal Antibody Therapy: A Propensity Score-Matched Cohort Study

Cooper et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofab512 (Peer Reviewed)

Retrospective 2,879 patients and matched controls in the USA, showing significantly lower mortality and hospitalization with bamlanivimab, bamlanivimab/etesevimab, and casirivimab/imdevimab. There was significantly lower hospitalization with casirivimab/imdevimab compared to bamlanivimab or bamlanivimab/etesevimab. PSM and multivariate analysis is only provided for all treatments combined.

risk of death, 77.5% lower, RR 0.23, p = 0.18, treatment 1 of 1,148 (0.1%), control 33 of 8,534 (0.4%), NNT 334, unadjusted.

risk of ICU admission, 47.5% lower, RR 0.52, p = 0.14, treatment 6 of 1,148 (0.5%), control 85 of 8,534 (1.0%), NNT 211, unadjusted.

risk of hospitalization, 52.4% lower, RR 0.48, p < 0.001, treatment 45 of 1,148 (3.9%), control 703 of 8,534 (8.2%), NNT 23, unadjusted.

Excluded in after exclusion results of meta analysis: unadjusted results with no group details.

Cooper et al., 10/8/2021, retrospective, USA, North America, peer-reviewed, 9 authors.

Real-World Effectiveness and Tolerability of Monoclonal Antibody Therapy for Ambulatory Patients with Early COVID-19

Webb et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofab331 (Peer Reviewed)

Retrospective 115 patients treated with casirivimab/imdevimab showing lower mortality, hospital admission, and emergency department visits with treatment. Authors falsely state that "no other COVID-19 therapies for ambulatory patients have proven effective".

risk of death, 98.3% lower, RR 0.02, p = 0.63, treatment 0 of 115 (0.0%), control 57 of 5,536 (1.0%), NNT 97, relative risk is not 0 because of continuity correction due to zero events.

risk of hospitalization, 91.1% lower, RR 0.09, p < 0.001, treatment 1 of 115 (0.9%), control 538 of 5,536 (9.7%), NNT 11.

Webb et al., 6/23/2021, retrospective, USA, North America, peer-reviewed, 14 authors.

Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Horby et al., medRxiv, doi:10.1101/2021.06.15.21258542 (Preprint)

RCT 9,785 hospitalized patients in the UK showing lower mortality with casirivimab/imdevimab, with statistical significance reached for baseline seronegative patients.

risk of death, 6.0% lower, RR 0.94, p = 0.17, treatment 944 of 4,839 (19.5%), control 1,026 of 4,946 (20.7%), NNT 81, all patients.

risk of mechanical ventilation, no change, RR 1.00, p = 1.00, treatment 479 of 4,556 (10.5%), control 487 of 4,642 (10.5%), all patients.

risk of death, 20.0% lower, RR 0.80, p = 0.001, treatment 396 of 1,633 (24.2%), control 451 of 1,520 (29.7%), NNT 18, seronegative patients.

risk of mechanical ventilation, 12.0% lower, RR 0.88, p = 0.18, treatment 189 of 1,599 (11.8%), control 200 of 1,484 (13.5%), NNT 60, seronegative patients.

Horby et al., 6/16/2021, Randomized Controlled Trial, United Kingdom, Europe, preprint, 34 authors.

REGEN-COV Antibody Combination and Outcomes in Outpatients with Covid-19

Weinreich et al., NEJM, doi:10.1056/NEJMoa2108163 (preprint 5/21/2021) (Peer Reviewed)

RCT 4,057 outpatients with >=1 risk factor for severe disease, showing significantly lower combined hospitalization/death, and significantly faster recovery with treatment. Median time from onset of symptoms 3 days. NCT04425629.

risk of death, 50.0% lower, RR 0.50, p = 0.45, treatment 2 of 2,091 (0.1%), control 4 of 2,089 (0.2%), NNT 1044, Table S9.

risk of death, 67.0% lower, RR 0.33, p = 0.37, treatment 1 of 1,355 (0.1%), control 3 of 1,341 (0.2%), NNT 667, 2400mg,Table S9.

risk of death, 1.6% higher, RR 1.02, p = 1.00, treatment 1 of 736 (0.1%), control 1 of 748 (0.1%), 1200mg,Table S9.

risk of death/hospitalization, 71.3% lower, RR 0.29, p < 0.001, treatment 18 of 1,355 (1.3%), control 62 of 1,341 (4.6%), NNT 30, 2400mg.

risk of death/hospitalization, 70.4% lower, RR 0.30, p = 0.002, treatment 7 of 736 (1.0%), control 24 of 748 (3.2%), NNT 44, 1200mg.

recovery time, 28.6% lower, relative time 0.71, p < 0.001, treatment 1,355, control 1,341, 2400mg.

recovery time, 28.6% lower, relative time 0.71, p < 0.001, treatment 736, control 748, 1200mg.

Weinreich et al., 5/21/2021, Randomized Controlled Trial, USA, North America, peer-reviewed, 39 authors, average treatment delay 3.0 days.

Subcutaneous REGEN-COV Antibody Combination to Prevent Covid-19

O'Brien et al., NEJM, doi:10.1056/NEJMoa2109682 (press release 4/12/21) (Peer Reviewed)

Prophylaxis trial reporting lower hospitalization/ER and symptomatic cases, and faster recovery with 1,200mg subcutaneous casirivimab with imdevimab. The same trial has updated results available in [1]. NCT04452318.

[1] c19regn.com/regeneron5.html

risk of hospitalization/ER, 88.9% lower, RR 0.11, p = 0.06, treatment 0 of 753 (0.0%), control 4 of 752 (0.5%), NNT 188, relative risk is not 0 because of continuity correction due to zero events, day 29.

risk of symptomatic case, 81.4% lower, RR 0.19, p < 0.001, treatment 11 of 753 (1.5%), control 59 of 752 (7.8%), NNT 16, day 29.

recovery time, 62.5% lower, relative time 0.37, p < 0.001, treatment 753, control 752, relative time with symptoms.

time to viral-, 69.2% lower, relative time 0.31, p < 0.001, treatment 753, control 752, relative time with high viral load.

O'Brien et al., 4/12/2021, Double Blind Randomized Controlled Trial, multiple countries, multiple regions, peer-reviewed, 36 authors.

New phase III data shows investigational antibody cocktail casirivimab and imdevimab reduced hospitalisation or death by 70% in non-hospitalised patients with COVID-19

Regeneron Press Release (Preprint)

Press release for new phase III data showing lower hospitalization/mortality, and faster symptom resolution among the subset of patients with at least one risk factor.

Some variants may escape antibodies [1].

[1] cell.com/cell/fulltext/S0092-8674(21)00367-6

risk of death/hospitalization, 71.3% lower, RR 0.29, p < 0.001, treatment 18 of 1,355 (1.3%), control 62 of 1,341 (4.6%), NNT 30, 2,400mg IV, >=1 risk factor.

risk of death/hospitalization, 70.4% lower, RR 0.30, p = 0.003, treatment 7 of 736 (1.0%), control 24 of 748 (3.2%), NNT 44, 1,200mg IV, >=1 risk factor.

recovery time, 28.6% lower, relative time 0.71, p < 0.001, treatment 1,355, control 1,341, 2,400mg IV, >=1 risk factor.

recovery time, 28.6% lower, relative time 0.71, p < 0.001, treatment 736, control 748, 1,200mg IV, >=1 risk factor.

Regeneron et al., 3/23/2021, Randomized Controlled Trial, USA, North America, preprint, 1 author.

Regeneron Reports Positive Interim Data with REGEN-COV™ Antibody Cocktail used as Passive Vaccine to Prevent COVID-19

Regeneron Press Release (Preprint)

Interim results of REGEN-COV prophylaxis showing 100% prevention of symptomatic infection (8/223 placebo vs. 0/186 REGEN-COV), and approximately 50% lower overall rates of infection (symptomatic and asymptomatic) (23/223 placebo vs. 10/186 REGEN-COV).

risk of symptomatic case, 93.6% lower, RR 0.06, p = 0.009, treatment 0 of 186 (0.0%), control 8 of 223 (3.6%), NNT 28, relative risk is not 0 because of continuity correction due to zero events.

risk of case, 47.9% lower, RR 0.52, p = 0.07, treatment 10 of 186 (5.4%), control 23 of 223 (10.3%), NNT 20.

Regeneron et al., 1/26/2021, Randomized Controlled Trial, USA, North America, preprint, 1 author.

Regeneron's REGN-COV2 antibody cocktail reduced viral levels and improved symptoms in non-hospitalized COVID-19 patients

Regeneron Press Release (Preprint)

Analysis of the first 275 patients in a trial of the REGN-COV2 antibody cocktail showing reductions in viral load and the time to alleviate symptoms in non-hospitalized patients with COVID-19. Greatest improvements were seen with patients that had not mounted their own effective immune response prior to treatment.

The mean time-weighted-average change from baseline nasopharyngeal viral load through Day 7 in the seronegative (no measurable antiviral antibodies) group was a 0.60 log10 copies/mL greater reduction (p=0.03) in patients treated with high dose, and a 0.51 log10 copies/mL greater reduction (p=0.06) in patients treated with low dose, compared to placebo. In the overall population, there was a 0.51 log10 copies/mL greater reduction (p=0.0049) in patients treated with high dose, and a 0.23 log10 copies/mL greater reduction (p=0.20) in patients treated with low dose, compared to placebo.

Among seronegative patients, median time to symptom alleviation (defined as symptoms becoming mild or absent) was 13 days in placebo, 8 days in high dose (p=0.22), and 6 days in low dose (p=0.09).

Adverse reactions were similar with treatment and placebo. There were no deaths.

recovery time, 38.0% lower, relative time 0.62, p = 0.22, treatment 92, control 91, high dose median time to recovery, group sizes estimated because they were not supplied.

recovery time, 54.0% lower, relative time 0.46, p = 0.09, treatment 92, control 91, low dose median time to recovery, group sizes estimated because they were not supplied.

Regeneron et al., 9/29/2020, Randomized Controlled Trial, USA, North America, preprint, 1 author.

Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies

Baum et al., Science, 21 Aug 2020, 369:6506, 1014-1018, doi:10.1126/science.abd0831 (Peer Reviewed) (In Vitro)

In Vitro study showing that, under pressure from individual antibodies, mutant viruses were rapidly selected that evaded the blocking function of all individual antibodies tested, including antibodies that potently bind to highly-conserved regions on the spike protein. However, escape mutants could not be efficiently generated following exposure to the REGN-COV2 cocktail since it utilizes two antibodies that can simultaneously bind to distinct regions of the RBD.

Baum et al., 8/21/2020, peer-reviewed, 17 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail

Hansen et al., Science, 21 Aug 2020, 369:6506, 1010-1014, doi:10.1126/science.abd0827 (Peer Reviewed)

Study using humanized mice and blood samples from recovered COVID-19 patients to generate antibodies targeting multiple different regions of the critical receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. The spike protein on the virus cell surface binds to the host cell and is required for infectivity. By blocking its interaction with the host cell, antibodies are able to neutralize the virus and block infection. Authors selected pairs of highly potent individual antibodies that simultaneously and non-competitively bind to the RBD. The multi-antibody approach is used to decrease the potential for the virus to escape.

Hansen et al., 8/21/2020, peer-reviewed, 47 authors.

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Aspirin	(meta)	Molnupiravir	(meta)
Bamlanivimab	(meta)	N-acetylcys..	(meta)
Bromhexine	(meta)	Nigella Sativa	(meta)
Budesonide	(meta)	Nitazoxanide	(meta)
Cannabidiol	(meta)	Paxlovid	(meta)
Casirivimab/i..	(meta)	Povidone-Iod..	(meta)
Colchicine	(meta)	Probiotics	(meta)
Conv. Plasma	(meta)	Proxalutamide	(meta)
Curcumin	(meta)	Quercetin	(meta)
Ensovibep	(meta)	Remdesivir	(meta)
Favipiravir	(meta)	Sotrovimab	(meta)
Fluvoxamine	(meta)	Vitamin A	(meta)
Hydroxychlor..	(meta)	Vitamin C	(meta)
Iota-carragee..	(meta)	Vitamin D	(meta)
Ivermectin	(meta)	Zinc	(meta)
Melatonin	(meta)

Other Treatments		Global Adoption