REGEN-COV rapidly protected household contacts from exposure to SARS-CoV-2 at home, with 72% protection against symptomatic infections in the first week, and 93% in subsequent weeks
Among individuals who developed symptomatic infections, REGEN-COV recipients cleared the virus faster and had much shorter symptom duration
Regeneron will share data with U.S. FDA and request EUA expansion to include COVID prevention for appropriate populations, using a 1,200 mg subcutaneous dose
Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced positive results from a Phase 3 trial (2069A) assessing the ability of REGEN-COV™ (casirivimab with imdevimab) to reduce the risk and burden of COVID-19 infection among household contacts of SARS-CoV-2 infected individuals. The trial, which was jointly run with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), met its primary and key secondary endpoints, showing that REGEN-COV 1,200 mg administered subcutaneously (SC) reduced the risk of symptomatic infections by 81% in those who were not infected when they entered the trial.
"These data suggest that REGEN-COV can complement widespread vaccination strategies, particularly for those at high risk of infection. Importantly, to date REGEN-COV has been shown in vitro to retain its potency against emerging COVID-19 variants of concern," said Myron Cohen, M.D., who leads the monoclonal antibody efforts for the NIH-sponsored COVID Prevention Network (CoVPN) and is Director of the Institute for Global Health & Infectious Diseases at the University of North Carolina at Chapel Hill. "Despite standard precautions to reduce transmission, nearly 10% of unvaccinated individuals living with an infected person developed symptomatic infections if they did not receive REGEN-COV. If authorized, convenient subcutaneous administration of REGEN-COV could help control outbreaks in high-risk settings where individuals have not yet been vaccinated, including individual households and group living settings."
The Phase 3, double-blind, placebo-controlled trial assessed the effect of REGEN-COV on uninfected individuals without anti-SARS-CoV-2 antibodies or any COVID-19 symptoms, who lived in the same household as an individual who tested positive for SARS-CoV-2 within the prior 4 days. The trial enrolled 1,505 people who were not infected with SARS-CoV-2 at baseline and randomized to receive either 1 dose of REGEN-COV (1,200 mg) or placebo, administered as SC injections.
"These findings are very encouraging and suggest that REGEN-COV is highly effective at preventing symptomatic COVID-19 in household contacts of SARS-CoV-2 infected individuals," said Dan H. Barouch, M.D., Ph.D., co-principal investigator of the trial and Director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center and Professor of Medicine at Harvard Medical School. "The rapid and robust protection, together with the subcutaneous route of administration, support the practical utility of these antibodies in protecting against COVID-19 in multiple settings, including after high-risk exposures. These antibodies may be particularly useful in individuals who are not yet vaccinated, and may also have potential in those who are immunosuppressed and may not respond well to vaccines."
On average, individuals treated with REGEN-COV who experienced a symptomatic infection resolved their symptoms in 1 week, compared to 3 weeks with placebo. Infected individuals also cleared the virus faster with REGEN-COV.
"With more than 60,000 Americans continuing to be diagnosed with COVID-19 every day, the REGEN-COV antibody cocktail may help provide immediate protection to unvaccinated people who are exposed to the virus, and we are also working to understand its potential to provide ongoing protection for immunocompromised patients who may not respond well to vaccines," said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron. "We thank the individuals, investigators and our collaborators involved in the trial, and look forward to rapidly discussing these results with regulatory authorities."
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TABLE: Key Results from Phase 3 Trial for the Prevention of COVID-19 in Uninfected Individuals1 | ||
|
REGEN-COV (single 1,200 mg dose) |
Placebo | |
|
n=753 |
n=752 | |
|
Risk of symptomatic SARS-CoV-2 infection | ||
|
Through day 29 (primary endpoint) | ||
|
Risk reduction |
81% (p<0.0001) | |
|
# of patients with events |
11 (1.5%) |
59 (7.8%) |
|
Within 1 week2 | ||
|
Risk reduction |
72% (nominal p=0.0002) | |
|
# of individuals with events |
9 (1.2%) |
32 (4.3%) |
|
Post-1 week2 | ||
|
Risk reduction |
93% (nominal p<0.0001) | |
|
# of individuals with events |
2 (0.3%) |
27 (3.6%) |
|
Symptoms and viral load | ||
|
Total weeks with symptoms | ||
|
Reduction |
93% (p<0.0001) | |
|
Total # of weeks (cumulative for all individuals in each arm) |
13 |
188 |
|
# of weeks with symptoms (average) in symptomatic individuals |
1.2 |
3.2 |
|
Total weeks with high viral load (>104 copies/mL) | ||
|
Reduction |
90% (p<0.0001) | |
|
Total # of weeks (cumulative for all individuals in each arm) |
14 |
136 |
|
# of weeks with high viral load (average) in qPCR positive subjects |
0.4 |
1.3 |
|
1. |
Based on the seronegative modified Full Analysis Set population, which includes all randomized subjects without evidence of current or prior SARS-CoV-2 infection (i.e., a negative RT-qPCR test and a negative antibody test) at randomization |
|
2. |
These analyses were not part of the pre-planned statistical analysis plan, so p-values are nominal |
Adverse events (AEs) occurred in 20% (n=265 out of 1,311) of REGEN-COV participants and 29% (n=379 out of 1,306) of placebo participants, and serious AEs occurred in 1% (n=10) of REGEN-COV and 1% (n=15) of placebo participants. There were 0 REGEN-COV and 4 placebo participants who were either hospitalized or visited the emergency room because of COVID-19 during the 29-day efficacy assessment period. Injection site reactions, all of which were grades 1-2, occurred in 4% (n=55) of REGEN-COV and 2% (n=19) of placebo participants. No individuals from either group withdrew from the trial due to AEs, and none of the deaths in the trial (2 REGEN-COV, 2 placebo) were attributed to COVID-19 or study drug.
REGEN-COV continues to be evaluated in clinical trials in multiple settings for COVID-19: for the prevention of COVID-19 in household contacts of infected individuals, and in non-hospitalized and certain hospitalized patients, including the open-label RECOVERY trial of hospitalized patients in the UK. As of April 2021, more than 25,000 people have participated in clinical trials involving REGEN-COV.
The development and manufacturing of REGEN-COV have been funded in part with federal funds from the Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, under OT number: HHSO100201700020C.
About the Multi-part Phase 3 Trial
To qualify for the joint Regeneron/NIAID multi-part Phase 3 trial, all participants were enrolled without any COVID-19 symptoms (asymptomatic) and lived in the same household as an individual who tested positive for SARS-CoV-2 within the prior 4 days. All participants were tested for SARS-CoV-2 at baseline using a RT-qPCR test from nasopharyngeal swabs. Participants with a negative test result joined the prevention trial (2069A) and participants with a positive test result joined the treatment trial (2069B).
All participants were then randomized (1:1) to receive either 1 dose of REGEN-COV (1,200 mg) or placebo, administered via 4 SC injections.
Among participants enrolled in the prevention trial, 41% were Latino/Hispanic and 9% were Black/African American. In total, 31% of participants had at least one known factor that put them at high risk of suffering severe consequences from COVID-19, as defined in the REGEN-COV fact sheet. In addition, 33% were obese and 38% were aged ³50 years (median age: 44 years; range: 12-92 years).
About the REGEN-COV Antibody Cocktail
REGEN-COV (casirivimab with imdevimab) is a cocktail of two monoclonal antibodies (also known as REGN10933 and REGN10987) that was designed specifically to block infectivity of SARS-CoV-2, the virus that causes COVID-19, using Regeneron's proprietary VelocImmune® and VelociSuite® technologies. The two potent, virus-neutralizing antibodies that form the cocktail 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.
Under an EUA issued by the U.S. Food and Drug Administration (FDA), REGEN-COV is currently available in the U.S. to treat mild-to-moderate COVID-19 in adults, as well as in pediatric patients at least 12 years of age and weighing at least 40 kg, who have received positive results of direct SARS-CoV-2 viral testing and are at high risk for progressing to severe COVID-19 and/or hospitalization. REGEN-COV has not been approved by the FDA but has been authorized for emergency use. This use is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use under section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.
REGEN-COV is currently authorized and available in a 2,400 mg IV dose, with infusion times as short as 20 minutes. The criteria for 'high-risk' patients are described in the Fact Sheet for Healthcare Providers. In the U.S., REGEN-COV is not authorized for use in patients who are hospitalized due to COVID-19 or require oxygen therapy, or for people currently using chronic oxygen therapy because of an underlying comorbidity who require an increase in baseline oxygen flow rate due to COVID-19.
Under this EUA, REGEN-COV is available throughout the U.S. – information on availability in your area is available from the Department of Health and Human Services and the National Infusion Center Association.
Regeneron is collaborating with Roche to increase global supply of REGEN-COV. Regeneron is responsible for development and distribution of the treatment in the U.S., and Roche is primarily responsible for development and distribution outside the U.S. The companies share a commitment to making the antibody cocktail available to COVID-19 patients around the globe and will support access in low- and lower-middle-income countries through drug donations to be made in partnership with public health organizations.
About Regeneron's VelocImmune Technology
Regeneron's VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron's co-Founder, President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create approximately a quarter of all original, FDA-approved fully human monoclonal antibodies currently available. This includes REGEN-COVTM (casirivimab with imdevimab), Dupixent® (dupilumab), Libtayo® (cemiplimab-rwlc), Praluent® (alirocumab), Kevzara® (sarilumab), Evkeeza™ (evinacumab-dgnb) and Inmazeb™ (atoltivimab, maftivimab and odesivimab-ebgn).
