Regeneron is applying our 30 years of scientific and technology expertise to combat the COVID-19 pandemic. We feel uniquely positioned to face this public health threat given our proprietary VelociSuite® technologies and our track record against infectious diseases such as Ebola. We have moved REGEN-COV™ (casirivimab and imdevimab) from discovery to late-stage clinical development and regulatory review in record time.
REGEN-COV™ (casirivimab and imdevimab) eligibility and treatment sites
The U.S. Food and Drug Administration (FDA) has granted an Emergency Use Authorization (EUA) for REGEN-COV™ (casirivimab and imdevimab) for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients (who are 12 years of age and older weighing at least 40 kg), with positive results of direct SARS-CoV-2 viral testing and who are at high risk of progression to severe COVID-19, including hospitalization or death.
REGEN-COV has not been approved but has been authorized for emergency use by the FDA. 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. Healthcare providers should review the Fact Sheet for Healthcare Providers for information on the authorized use of REGEN-COV.
Limitations of Authorized Use
REGEN-COV is not authorized for use in patients who are hospitalized due to COVID-19, who require oxygen therapy due to COVID-19, or who require an increase in baseline oxygen flow rate due to COVID-19 in those on chronic oxygen therapy due to underlying non-COVID-19 related comorbidity.
Benefit of treatment with REGEN-COV has not been observed in patients hospitalized due to COVID-19. Monoclonal antibodies, such as REGEN-COV, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high-flow oxygen or mechanical ventilation.
Please see below for Important Safety Information.
Have you been diagnosed with COVID-19? Find a site with antibody medicines:
Regeneron is collaborating with Roche to increase global supply of REGEN-COV, with expected production of at least 2 million treatment doses per year, beginning in 2021. 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.
Ongoing clinical and preclinical research
REGEN-COV clinical trial by
We are studying REGEN-COV in multiple patient populations for the potential treatment and prevention of COVID-19. We are sharing data from these ongoing clinical trials as quickly as possible with the public and regulatory authorities.
Data is available on REGEN-COV in various patient populations:
Non-hospitalized patients: Data from an ongoing seamless trial assessed the effect of REGEN-COV on reducing viral load and patient medical visits in high-risk, non-hospitalized patients.
Hospitalized patients: Initial data for futility analyses evaluated REGEN-COV based on the ability to reduce incidence of death or mechanical ventilation in hospitalized patients on low-flow oxygen.
Prevention of symptomatic disease: Phase 3 data assessing the ability of REGEN-COV to reduce the risk and burden of COVID-19 infection among household contacts of SARS-CoV-2 infected individuals.
SARS-CoV-2 variants: Academic researchers and Regeneron scientists independently confirmed in in vitro studies that REGEN-COV successfully neutralizes the circulating SARS-CoV-2 variants B.1.1.7 (first identified in the UK, which is now classified by the World Health Organization [WHO] as Alpha) and B.1.351 (first identified in South Africa, which is now classified by the WHO as Beta). Similarly, the FDA authorized factsheet for Health Care Providers affirms that REGEN-COV retains potency against the variants first identified in the UK, South Africa, Brazil, California, New York or India, which are now classified by the WHO as Alpha, Beta, Gamma, Iota, Epsilon and Delta respectively. This finding is based on in vitro pseudovirus studies, and it is not known how pseudovirus data correlate with clinical outcomes. Consequently, REGEN-COV remains available for use in all 50 states.
Monitor SARS-CoV-2 variants with Regeneron’s COVID-19 Dashboard
Refreshed daily with new genomes and associated patient metadata.Find out more
The combined frequency of the P.1 variant (first identified in Brazil, now classified by the WHO as Gamma) and B.1.351 variant (first identified in South Africa, now classified by the WHO as Beta) now exceeds 10% of new COVID-19 diagnoses across eight states (Arizona, California, Florida, Illinois, Indiana, Massachusetts, Oregon and Washington), and the prevalence of these and other variants continues to be closely monitored.
With two complementary antibodies in one therapeutic, even if one antibody has reduced potency in response to a variant strain of the virus, the risk of the combination losing efficacy is diminished, as the virus would need to mutate in multiple distinct locations to evade both antibodies. We have hundreds of additional investigational potent, neutralizing antibodies in our labs that could form new combinations that might be useful against future variants, and we are evaluating potential next steps with these novel early-stage candidates.
- New England Journal of Medicine: “REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19” details initial clinical data from a seamless Phase 1/2/3 trial of the antibody cocktail in non-hospitalized patients with COVID-19, showing that casirivimab and imdevimab effectively reduced viral load and the need for medically-attended visits, with the greatest benefit in patients who had not yet mounted their own effective immune response or had high viral load at baseline.
- Science: "Studies in Humanized Mice and Convalescent Humans Yield a SARS-CoV-2 Antibody Cocktail” describes Regeneron's parallel efforts using both humanized VelocImmune® mice and blood samples from recovered COVID-19 patients to generate a large and diverse collection of antibodies targeting multiple different regions of the critical receptor-binding domain (RBD) of the SARS-CoV-2 spike protein.
- Science: "Antibody Cocktail to SARS-Cov-2 Spike Protein Prevents Rapid Mutational Escape Seen with Individual Antibodies" demonstrates 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 casirivimab and imdevimab cocktail since it utilizes two antibodies that can simultaneously bind to distinct regions of the virus. The clinical significance of these findings is unknown.
- Science: “REGN-COV2 Antibody Cocktail Prevents and Treats SARS-CoV-2 Infection in Rhesus Macaques and Hamsters” demonstrates the efficacy of our antibody cocktail in non-human primates and hamsters, showing its ability to reduce virus load in lower and upper airways and decrease virus-induced pathological impact.
Our antibody cocktail approach to infectious disease
Regeneron’s infectious disease programs have led to an approved medicine for Ebola, an emergency authorized medicine for COVID-19 and an investigational medicine for Middle East Respiratory Syndrome (MERS). In each case, we have taken a strategic multi-antibody ‘cocktail’ approach.
Our COVID-19-related discovery efforts started in early 2020, when we utilized our VelociSuite® technologies to produce and evaluate hundreds of virus-neutralizing antibodies in our genetically engineered mice. Knowing from the beginning that we would take a combination approach, we also identified similarly-performing antibodies from human COVID-19 survivors in order to maximize the pool of potential candidates. By June, we had selected and progressed the two potent, complementary and non-competing antibodies, casirivimab and imdevimab, into large-scale manufacturing and clinical trials.
Viruses, by their nature, mutate over time leading to variant forms. With two (or more) complementary antibodies in one therapeutic, even if one antibody has reduced potency in response to a certain strain, the risk of the combination losing efficacy is diminished since the virus would need to mutate in multiple distinct locations to evade both antibodies. In the case of REGEN-COV for COVID-19, casirivimab and imdevimab bind tightly and non-competitively to different, non-overlapping parts of the spike protein of the SARS-CoV-2 virus, thereby blocking the virus’ ability to infect healthy cells.
The REGEN-COV antibody cocktail was prospectively designed so that if variants arose affecting one component, the other component could compensate and still allow for potent neutralizing activity. In fact, as reported in ‘Science’ in June 2020, Regeneron scientists predicted the key mutation that has since appeared in the SARS-CoV-2 variants first identified in South Africa and Brazil, and further showed that this mutation would lower potency of the casirivimab antibody, but be compensated for by the strong potency of the imdevimab antibody.
Business updatesOur operations
In response to the COVID-19 pandemic, we implemented changes in our business beginning in March 2020 to protect our employees and support appropriate health and safety protocols. For example, we have implemented work-from-home policies for a significant portion of our employees. For these remote employees, we provide ergonomic evaluations of at-home workstations, support information technology needs, and provide guidance for managers to ensure that employees remain connected and maintain physical, mental and emotional wellbeing. For our essential employees who remain onsite in our laboratories and manufacturing facilities, we provide personal protective equipment and require masks to be worn; we have also implemented increased physical distancing in workspaces and enhanced cleaning protocols. We currently administer COVID-19 tests to all onsite employees and contractors weekly and have been regularly administering these tests for designated employees since the spring of 2020. For any employee who contracts or is exposed to COVID-19, we provide full pay for their entire recovery and quarantine time.Our community support
Regeneron’s community response focuses on raising critical funds, mobilizing resources and supporting the most vulnerable nonprofits, people and communities around the world. Since 2020, we have provided nearly $2 million in financial support and in-kind donations. As part of our Regeneron COVID-19 Double Matching Relief Campaign, we supported our employees’ giving and select charities by raising $750,000. In Westchester County, we are supporting Afya Foundation which serves as the county’s ancillary PPE supply hub, managing the procurement and distribution of PPE to vulnerable community agencies and federally qualified health centers in need. We are supporting local nonprofits’ capacity and sustainability and COVID aid funds to provide broad financial relief and vital services to patients. Regeneron’s Industrial Operations and Product Supply (IOPS) team assisted New York State by making and donating viral transport media (VTM), a critical component of COVID-19 testing kits that has been in short supply.
From discovery to large-scale manufacturing, our VelociSuite® technologies uniquely enable our discovery and development efforts.
2020 was a challenging year for everyone. Our founder, CEO and president, Len Schleifer, MD, PhD, reflects on what enabled our COVID-19 work, what we accomplished and what is yet to come.
REGEN-COV (casirivimab and imdevimab) is an investigational therapy and has been authorized by the FDA for the emergency use described herein. Casirivimab and imdevimab must be administered together. REGEN-COV is not FDA approved for any use. Safety and effectiveness of REGEN-COV has not been fully established for the treatment of COVID-19.
Important Safety Information
REGEN-COV (casirivimab and imdevimab) is an unapproved investigational therapy, and there are limited clinical data available. Serious and unexpected adverse events may occur that have not been previously reported with REGEN-COV use.
Warnings and Precautions
Hypersensitivity Reactions Including Anaphylaxis and Infusion-Related Reactions: Serious hypersensitivity reactions, including anaphylaxis, have been observed with administration of REGEN-COV. If signs or symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive therapy. Hypersensitivity reactions occurring more than 24 hours after the infusion have also been reported with the use of REGEN-COV under EUA. Infusion-related reactions, occurring during the infusion and up to 24 hours after the infusion, have been observed with administration of REGEN-COV. These reactions may be severe or life threatening
- Signs and symptoms of infusion-related reactions may include: fever, difficulty breathing, reduced oxygen saturation, chills, nausea, arrythmia (e.g., atrial fibrillation, tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, headache, bronchospasm, hypotension, hypertension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, vasovagal reactions (e.g., pre-syncope, syncope), dizziness, fatigue and diaphoresis. Consider slowing or stopping the infusion and administer appropriate medications and/or supportive care if an infusion-related reaction occurs
- Clinical Worsening After REGEN-COV Administration: Clinical worsening of COVID-19 after administration of REGEN-COV has been reported and may include signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrythmia (e.g., atrial fibrillation, tachycardia, bradycardia), fatigue, and altered mental status. Some of these events required hospitalization. It is not known if these events were related to REGEN-COV use or were due to progression of COVID-19
- Limitations of Benefit and Potential for Risk in Patients with Severe COVID-19: Benefit of treatment with REGEN-COV has not been observed in patients hospitalized due to COVID-19. Monoclonal antibodies, such as REGEN-COV, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high-flow oxygen or mechanical ventilation. Therefore, REGEN-COV is not authorized for use in patients who are hospitalized due to COVID-19, OR who require oxygen therapy due to COVID-19, OR who require an increase in baseline oxygen flow rate due to COVID-19 in those on chronic oxygen therapy due to underlying non-COVID-19–related comorbidity
- Hypersensitivity Reactions Including Anaphylaxis and Infusion-Related Reactions: Serious hypersensitivity reactions, including anaphylaxis, have been observed with administration of REGEN-COV. If signs or symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive therapy. Hypersensitivity reactions occurring more than 24 hours after the infusion have also been reported with the use of REGEN-COV under EUA. Infusion-related reactions, occurring during the infusion and up to 24 hours after the infusion, have been observed with administration of REGEN-COV. These reactions may be severe or life threatening
- In a pooled phase 1/2/3 analysis of COV-2067, infusion-related reactions (adverse event assessed as causally related by the investigator) of grade 2 or higher severity have been observed in 10/4,206 (0.2%) of those who received REGEN-COV at the authorized dose or a higher dose
- Overall, in Phase 1/2/3, three subjects receiving the 8,000 mg dose of REGEN-COV, and one subject receiving the 1,200 mg casirivimab and 1,200 mg imdevimab, had infusion-related reactions (urticaria, pruritus, flushing, pyrexia, shortness of breath, chest tightness, nausea, vomiting, rash) which resulted in permanent discontinuation of the infusion. All events resolved
- Anaphylactic reactions have been reported in the clinical program in subjects receiving REGEN-COV. The events began within 1 hour of completion of the infusion, and in at least one case required treatment including epinephrine. The events resolved
- The safety with subcutaneous administration is based on analysis from HV-2093, a randomized double-blind, placebo-controlled trial evaluating the safety and pharmacokinetic profile in healthy volunteer adult subjects. Subjects were randomized 3:1 to REGEN-COV (n=729) or placebo (n=240). Injection site reactions were observed in 12% and 4% of subjects following single dose administration in the casirivimab and imdevimab, and placebo arms respectively; the remaining safety findings with subcutaneous administration in the casirivimab and imdevimab arm were similar to the safety findings observed with intravenous administration in COV-2067
- Patient Monitoring Recommendations: Clinically monitor patients during infusion and observe patients for at least 1 hour after intravenous infusion or subcutaneous dosing is complete
Use in Specific Populations:
- Pregnancy: There are insufficient data to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. REGEN-COV should only be used during pregnancy if the potential benefit outweighs the potential risk for the mother and the fetus
- Lactation: There are no available data on the presence of casirivimab and/or imdevimab in human milk or animal milk, the effects on the breastfed infant, or the effects of the drug on milk production. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for REGEN-COV and any potential adverse effects on the breastfed child from REGEN-COV or from the underlying maternal condition