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2 COVID Outpatient Antibody Treatments Report Today
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Lilly treatment - SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19 October 28, 2020
In this ongoing phase 2 trial involving outpatients with recently diagnosed mild or moderate Covid-19, we randomly assigned 452 patients to receive a single intravenous infusion of neutralizing antibody LY-CoV555 in one of three doses (700 mg, 2800 mg, or 7000 mg) or placebo and evaluated the quantitative virologic end points and clinical outcomes. The primary outcome was the change from baseline in the viral load at day 11. The results of a preplanned interim analysis as of September 5, 2020, are reported here. In this preplanned interim analysis of the BLAZE-1 trial, we examined the efficacy of LY-CoV555 in the treatment of mild or moderate Covid-19. The trial was designed to enroll patients with a recent disease onset to evaluate the effect of early intervention with antibody therapy on viral-load biomarkers, symptoms, and severe clinical outcomes, such as hospitalization and death.
Results
At the time of the interim analysis, the observed mean decrease from baseline in the log viral load for the entire population was -3.81, for an elimination of more than 99.97% of viral RNA. For patients who received the 2800-mg dose of LY-CoV555, the difference from placebo in the decrease from baseline was -0.53 (95% confidence interval [CI], -0.98 to -0.08; P=0.02), for a viral load that was lower by a factor of 3.4. Smaller differences from placebo in the change from baseline were observed among the patients who received the 700-mg dose (-0.20; 95% CI, -0.66 to 0.25; P=0.38) or the 7000-mg dose (0.09; 95% CI, -0.37 to 0.55; P=0.70). On days 2 to 6, the patients who received LY-CoV555 had a slightly lower severity of symptoms than those who received placebo. The percentage of patients who had a Covid-19–related hospitalization or visit to an emergency department was 1.6% in the LY-CoV555 group and 6.3% in the placebo group. Among the patients who received LY-CoV555, the viral load at day 11 (the primary outcome) was lower than that in the placebo group only among those who received the 2800-mg dose. However, a decreased viral load at day 11 did not appear to be a clinically meaningful end point, since the viral load was substantially reduced from baseline for the majority of patients, including those in the placebo group, a finding that was consistent with the natural course of the disease.....
https://www.nejm.org/doi/full/10.1056/NEJMoa2029849
Conclusions
In this interim analysis of a phase 2 trial, one of three doses of neutralizing antibody LY-CoV555 appeared to accelerate the natural decline in viral load over time, whereas the other doses had not by day 11.
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October 28, 2020
Regeneron's COVID-19 Outpatient Trial Prospectively Demonstrates that REGN-COV2 Antibody Cocktail Significantly Reduced Virus Levels and Need for Further Medical Attention
TARRYTOWN, N.Y., Oct. 28, 2020 /PRNewswire/ --
Today's data, involving an additional 524 patients from the ongoing Phase 2/3 trial, provides definitive final virology results and meets the clinical endpoint of reducing medical visits
Regeneron has shared these results with the U.S. FDA, which is reviewing an Emergency Use Authorization submission for the REGN-COV2 low dose in adults with mild-to-moderate COVID-19 who are at high risk for poor outcomes
Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced positive, prospective results from an ongoing Phase 2/3 seamless trial in the COVID-19 outpatient setting showing its investigational antibody cocktail, REGN-COV2, met the primary and key secondary endpoints. REGN-COV2 significantly reduced viral load and patient medical visits (hospitalizations, emergency room, urgent care visits and/or physician office/telemedicine visits).
"The first job of an antiviral therapeutic drug is to lower the viral load, and our initial data in 275 patients strongly suggested that the REGN-COV2 antibody cocktail could lower viral load and thereby potentially improve clinical outcomes. Today's analysis, involving more than 500 additional patients, prospectively confirms that REGN-COV2 can indeed significantly reduce viral load and further shows that these viral reductions are associated with a significant decrease in the need for further medical attention," said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer of Regeneron. "We continue to see the strongest effects in patients who are most at risk for poor outcomes due to high viral load, ineffective antibody immune response at baseline, or pre-existing risk factors. Regeneron has shared these results with the U.S. Food and Drug Administration as part of its review of our Emergency Use Authorization submission, and we continue to focus on completing our ongoing trials evaluating REGN-COV2 for the treatment and prevention of COVID-19."
The randomized, double-blind trial is measuring the effect of adding REGN-COV2 to usual standard-of-care, compared to adding placebo to standard-of-care. A descriptive analysis from the first 275 patients was previously reported. Today's data, involving an additional 524 patients, show the trial met all of the first nine endpoints in the statistical hierarchy, which assessed virologic endpoints based on viral load, seronegative status and dose group, as well as the key clinical endpoint of COVID-19 related medically-attended visits, in patients who had laboratory-confirmed COVID-19 at baseline. Results showed no significant difference in virologic or clinical efficacy between the REGN-COV2 high dose (8 grams) and low dose (2.4 grams). Based on this finding, Regeneron is reviewing potential changes to dosing in the ongoing outpatient clinical trial given the current limited supply of REGN-COV2.
Virologic results (n=524, prospectively confirming previous 275-patient analysis):
• On the primary endpoint, the average daily change in viral load through day 7 (mean time-weighted average change from baseline) in patients with high viral load (defined as greater than107 copies/mL) was a 0.68 log10 copies/mL greater reduction with REGN-COV2 compared to placebo (combined dose groups; p<0.0001). There was a 1.08 log greater reduction with REGN-COV2 treatment by day 5, which corresponds to REGN-COV2 patients having, on average, a greater than 10-fold reduction in viral load, compared to placebo.
• In the overall patient group with detectable virus at baseline, the average daily reduction in viral load through day 7 was a 0.36 log10 copies/mL greater reduction with REGN-COV2 compared to placebo (combined dose groups; p=0.0003).
• As in the earlier analysis, patients with higher viral load at baseline and/or no detectable antibodies at baseline (suggesting their bodies had not yet mounted an effective immune response), derived greater benefit from REGN-COV2 therapy.
Clinical results in the overall population (n=799):
• On the key clinical endpoint, treatment with REGN-COV2 reduced COVID-19 related medical visits by 57% through day 29 (2.8% combined dose groups; 6.5% placebo; p=0.024).
• Treatment with REGN-COV2 reduced COVID-19 related medical visits by 72% in patients with one or more risk factor (including being over 50 years of age; body mass index greater than 30; cardiovascular, metabolic, lung, liver or kidney disease; or immunocompromised status) (combined dose groups; nominal p = 0.0065).
There was no planned formal statistical analysis of symptom alleviation in this analysis; descriptive analyses did not reveal robust associations with viral load, serology status or treatment. REGN-COV2 was well tolerated in the trial. Serious adverse events were numerically more frequent with placebo than REGN-COV2 treatment (0.8% high dose, 1.6% low dose; 2.3% placebo). Numerically more infusion reactions occurred with the REGN-COV2 high dose compared to placebo (1.5% high dose; 0% low dose; 0.4% placebo).
"We will submit detailed results from this trial for publication in order to share insights with the public health and medical communities," said David Weinreich, M.D., Senior Vice President and Head of Global Clinical Development at Regeneron. "We would like to thank the global investigators, sites and patients who continue to work with us to conduct REGN-COV2 trials across different settings and geographies."
Additional Trial Background
In the overall patient population (n=799), patients were prospectively characterized prior to treatment by serology tests to see if they had already generated antiviral antibodies on their own and were thus classified as seronegative (no measurable antiviral antibodies) or seropositive (measurable antiviral antibodies). Approximately 38% of patients were seropositive, 51% were seronegative and 11% were categorized as "other" due to unclear or unknown serology status. Approximately 50% of patients were Hispanic, 9% were African American and 60.5% had one or more underlying risk factors for severe COVID-19, including obesity (37%). On average, patients were 42.2 years of age. In total, 47% of participants were male and 53% were female.
The Phase 3 portion of this trial continues in non-hospitalized patients. REGN-COV2 is also being studied in a Phase 2/3 clinical trial for the treatment of COVID-19 in hospitalized patients, the Phase 3 open-label RECOVERY trial of hospitalized patients in the UK and a Phase 3 trial for the prevention of COVID-19 in household contacts of infected individuals.
About REGN-COV2
REGN-COV2 is a combination of two monoclonal antibodies (REGN10933 and REGN10987) and was designed specifically to block infectivity of SARS-CoV-2, the virus that causes COVID-19.
To develop REGN-COV2, Regeneron scientists evaluated thousands of fully-human antibodies produced by the company's VelocImmune® mice, which have been genetically modified to have a human immune system, as well as antibodies identified from humans who have recovered from COVID-19. The two potent, virus-neutralizing antibodies that form REGN-COV2 bind non-competitively to the critical receptor binding domain of the virus's spike protein, which diminishes the ability of mutant viruses to escape treatment and protects against spike variants that have arisen in the human population, as detailed in Science.
REGN-COV2's development and manufacturing has been funded in part with federal funds from the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response at the U.S. Department of Health and Human Services under OT number:
HHSO100201700020C. Regeneron has partnered with Roche to increase the global supply of REGN-COV2 beginning in 2021. If REGN-COV2 proves safe and effective in clinical trials and regulatory approvals are granted, Regeneron will manufacture and distribute it in the U.S. and Roche will develop, manufacture and distribute it outside the U.S.
https://newsroom.regeneron.com/news-releases/news-release-details/regenerons-covid-19-outpatient-trial-prospectively-demonstrates
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