New Phase 3 Analyses Show That a Single Dose of REGEN-COV® (casirivimab and imdevimab) Provides Long-term Protection Against COVID-19
Single dose of REGEN-COV (1,200 mg subcutaneous) reduced the risk of COVID-19 by 81.6% during the pre-specified follow-up period (months 2-8), maintaining the 81.4% risk reduction previously reported during month 1
During the 8-month assessment period there were 0 hospitalizations for COVID-19 in the REGEN-COV group and 6 in the placebo group
The fully human antibodies in REGEN-COV were developed to provide long-lasting protective effects without any artificial mutations or sequences
"Today's new data demonstrate how a single dose of REGEN-COV can help protect people from COVID-19 for many months after administration," said
In results previously published, the trial met its primary endpoint, reducing the risk of COVID-19 (i.e., laboratory-confirmed symptomatic SARS-CoV-2 infections) by 81.4% within 1 month of receiving REGEN-COV (p<0.0001). The new results released today describe a pre-specified analysis for the following 7 months, throughout which an additional 45 symptomatic infections occurred. During this time period, REGEN-COV continued to prevent infection, without requiring additional doses. Compared to placebo (n=842), people who received a single dose of REGEN-COV (n=841) experienced:
- 81.6% reduced risk of developing COVID-19 during the pre-specified follow-up period, between months 2-8 (7 REGEN-COV, 38 placebo; 95% confidence interval [CI]: 59.8%, 91.6%; nominal p<0.0001).
- 81.5% reduced risk of developing COVID-19 at any time during the 8 months after receiving REGEN-COV (20 REGEN-COV, 108 placebo; 95% CI: 70.6%,88.4%; nominal p<0.0001).
- During the 8-month assessment period, 0 individuals in the REGEN-COV group were hospitalized due to COVID-19, compared to 6 individuals in the placebo group (1 person in the first month; 5 people during months 2-8). There were no deaths due to COVID-19 in any treatment group during the 8-month assessment period, and there were no new safety signals identified for REGEN-COV.
The trial, which was fully enrolled in early 2021, allowed participants to become vaccinated if they wished once the primary efficacy treatment period (month 1) was complete. Vaccination rates during the months 2-8 assessment period were balanced, with 34.5% (n=290) of the REGEN-COV group and 35.2% (n=296) of the placebo group receiving at least 1 COVID-19 vaccine dose by the end of the 8-month assessment period.
Through an innovative trial design, researchers were able to demonstrate the impact of REGEN-COV in high-risk household transmission settings (month 1, both pre- and post-exposure prophylaxis), as well as after the immediate risk of household infection had subsided (months 2-8, pre-exposure prophylaxis), when most infections were presumably acquired in the broader community. During the initial high-risk period related to household transmission, the rate of COVID-19 (in the absence of protection with REGEN-COV) was 13-fold higher than during the subsequent period of ongoing transmission: during month 1, the rate of COVID-19 in the placebo group was 8.3% per month; and during months 2-8 it decreased to 0.6% per month on average.
"In this trial, a single dose of REGEN-COV provided long-term protection against COVID-19, including times of particularly high risk from household exposure, and in the longer-term during ongoing broader exposure," said
REGEN-COV is currently authorized in the
The development and manufacturing of REGEN-COV have been funded in part with federal funds from the
Regeneron is collaborating with Roche to increase global supply of the antibody cocktail, with Roche primarily responsible for development and distribution outside the
About the Trial
The Phase 3 double-blind, placebo-controlled trial enrolled people who lived in the same household as an individual who was diagnosed with 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 and for the presence of antibodies using serum antibody testing. Participants were randomized (1:1) to receive either 1 dose of REGEN-COV (1,200 mg) or placebo, administered via 4 subcutaneous injections.
During the trial, participants were tested weekly for SARS-CoV-2 during the initial month (4 weeks), as part of the primary analyses. Following this, from months 2-8 (week 5 to week 32), participants were to be tested if they developed any COVID-19 symptoms.
The new analyses include results from 1,683 people who were not infected with SARS-CoV-2 and did not have antibodies for SARS-CoV-2 (seronegative) at baseline. Across both groups approximately 95% completed the trial. In total, 42% identified as Hispanic/Latino and 9% identified as Black/
About the REGEN-COV Antibody Cocktail
REGEN-COV (casirivimab and imdevimab) is a cocktail of two monoclonal antibodies 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 Cell and Science.
REGEN-COV has not been approved by the FDA, but is currently authorized in the
In October, the
Emergency or temporary pandemic use authorizations are currently in place in more than 40 countries, including the
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 President and Chief Scientific Officer
AUTHORIZED USES AND IMPORTANT SAFETY INFORMATION
REGEN-COV is authorized for the treatment of mild to moderate coronavirus disease 2019 (COVID-19) in adults and pediatric patients (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 for progression to severe COVID-19, including hospitalization or death
Limitations of Authorized Use (Treatment)
- 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
- 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
REGEN-COV is authorized in adult and pediatric individuals (12 years of age and older weighing at least 40 kg) for post-exposure prophylaxis of COVID-19 in individuals who are at high risk for progression to severe COVID-19, including hospitalization or death, and are:
- not fully vaccinated or who are not expected to mount an adequate immune response to complete SARS-CoV-2 vaccination (for example, individuals with immunocompromising conditions including those taking immunosuppressive medications) and
- have been exposed to an individual infected with SARS-CoV-2 consistent with close contact criteria per
Centers for Disease Control and Prevention( CDC) or
- who are at high risk of exposure to an individual infected with SARS-CoV-2 because of occurrence of SARS-CoV-2 infection in other individuals in the same institutional setting (for example, nursing homes, prisons)
Limitations of Authorized Use (Post-Exposure Prophylaxis)
- Post-exposure prophylaxis with REGEN-COV is not a substitute for vaccination against COVID-19
- REGEN-COV is not authorized for pre-exposure prophylaxis for prevention of COVID-19
REGEN-COV has not been approved, but has been authorized for emergency use by FDA
These uses are 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 uses of REGEN-COV and mandatory requirements of the EUA and must comply with the requirements of the EUA. The FDA Letter of Authorization is available for reference, as well as the Dear Healthcare Provider Letter and Patient Fact Sheet
Criteria for Identifying High Risk Individuals
Please refer to the Fact Sheet for Healthcare Providers for criteria for identifying high risk individuals
SARS-CoV-2 Viral Variants
Circulating SARS-CoV-2 viral variants may be associated with resistance to monoclonal antibodies. Healthcare providers should review the Antiviral Resistance information in Section 15 of the Fact Sheet for details regarding specific variants and resistance, and refer to the
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
REGEN-COV is contraindicated in individuals with previous severe hypersensitivity reactions, including anaphylaxis, to REGEN-COV
- Warnings and Precautions:
- Hypersensitivity 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, arrhythmia (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, arrhythmia (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: 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
- Adverse Reactions:
- COV-2067 (Treatment): 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. 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
- COV-2069 (Post-exposure prophylaxis): In subjects who were SARS-CoV-2 negative at baseline (Cohort A), injection site reactions (all grade 1 and 2) occurred in 55 subjects (4%) in the REGEN-COV group and 19 subjects (2%) in the placebo group. The most common signs and symptoms of injection site reactions which occurred in at least 1% of subjects in the REGEN-COV group were erythema and pruritus. Hypersensitivity reactions occurred in 2 subjects (0.2%) in the REGEN-COV group and all hypersensitivity reactions were grade 1 in severity. In subjects who were SARS-CoV-2 positive at baseline (Cohort B), injection site reactions, all of which were grade 1 or 2, occurred in 6 subjects (4%) in the REGEN-COV group and 1 subject (1%) in the placebo group. The most common signs and symptoms of injection site reactions which occurred in at least 1% of subjects in the REGEN-COV group were ecchymosis and erythema
- COV-2093 (Subcutaneous Dosing): Injection site reactions occurred in 12% and 4% of subjects following single dose administration in the REGEN-COV and placebo groups, respectively. Remaining safety finding following subcutaneous administration in the REGEN-COV group were similar to the safety findings observed with intravenous administration in COV-2067. With repeat dosing, injection site reactions occurred in 252 subjects (35%) in the REGEN-COV group and 38 subjects (16%) in the placebo group; all injection site reactions were grade 1 or 2 in severity. Hypersensitivity reactions occurred in 8 subjects (1%) in the REGEN-COV group; and all hypersensitivity reactions were grade 1 or 2 in severity. There were no cases of anaphylaxis
- Patient Monitoring Recommendations: Clinically monitor patients during dose administration 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
Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite technologies, such as VelocImmune, which uses unique genetically humanized mice to produce optimized fully human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center, which is conducting one of the largest genetics sequencing efforts in the world.
For additional information about the company, please visit www.regeneron.com or follow @Regeneron on Twitter.
Forward-Looking Statements and Use of Digital Media
This press release includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron Pharmaceuticals, Inc. ("Regeneron" or the "Company"), and actual events or results may differ materially from these forward-looking statements. Words such as "anticipate," "expect," "intend," "plan," "believe," "seek," "estimate," variations of such words, and similar expressions are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. These statements concern, and these risks and uncertainties include, among others, the impact of SARS-CoV-2 (the virus that has caused the COVID-19 pandemic) on Regeneron's business and its employees, collaborators, and suppliers and other third parties on which Regeneron relies, Regeneron's and its collaborators' ability to continue to conduct research and clinical programs, Regeneron's ability to manage its supply chain, net product sales of products marketed or otherwise commercialized by Regeneron and/or its collaborators or licensees (collectively, "Regeneron's Products"), and the global economy; the nature, timing, and possible success and therapeutic applications of Regeneron's Products and product candidates being developed by Regeneron and/or its collaborators or licensees (collectively, "Regeneron's Product Candidates") and research and clinical programs now underway or planned, including without limitation the development program relating to the REGEN-COV® (casirivimab and imdevimab) antibody cocktail (including any potential approval of REGEN-COV for pre-exposure prophylaxis and/or the treatment for hospitalized patients); uncertainty of the utilization, market acceptance, and commercial success of Regeneron's Products and Regeneron's Product Candidates (such as REGEN-COV), including the impact of recommendations, guidelines, or studies (whether conducted by Regeneron or others and whether mandated or voluntary), such as the study discussed in this press release, on any of the foregoing or any potential regulatory approval of Regeneron's Products and Regeneron's Product Candidates; the likelihood, timing, and scope of possible regulatory approval and commercial launch of Regeneron's Product Candidates (such as REGEN-COV, including based on the Biologics License Applications filed or planned to be filed with the
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