Regeneron Pharmaceuticals, Inc.today announced that the U.S. Department of Health and Human Services (HHS) and the Department of Defense (DOD) will purchase 1.4 million additional doses of REGEN-COV (casirivimab and imdevimab). The government will continue to provide REGEN-COV at no cost to patients.
"More than a year and a half into this pandemic, too many people are still being hospitalized and dying due to COVID-19," said Leonard S. Schleifer, M.D., Ph.D., President and Chief Executive Officer of Regeneron. "While vaccination remains the first line of defense to decrease the burden of COVID-19, REGEN-COV is a key tool that reduces the risk of hospitalization or death by 70% in high-risk individuals when given early in the course of the infection. Recently there has been greater demand for REGEN-COV, and we will provide additional doses to the U.S. government as quickly as possible."
Under the new agreement, Regeneron will supply an additional 1.4 million 1,200 mg doses of REGEN-COV to the U.S. government by January 31, 2022, at a cost of $2,100 per dose. This new agreement follows two earlier agreements with the U.S. government announced in July 2020 and January 2021.
REGEN-COV is an investigational medicine authorized by the U.S. Food and Drug Administration (FDA) under an emergency use authorization to treat people who are at high risk of serious consequences from COVID-19 infection who are either already infected (non-hospitalized) or in certain post-exposure prophylaxis settings.
In addition, the robust REGEN-COV development program has reported positive Phase 3 trial results across the spectrum of COVID-19 infection, from prevention to hospitalization:
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 HHS's Office of the Assistant Secretary for Preparedness and Response, under OT number: HHSO100201700020C.
Regeneron invented REGEN-COV and is collaborating with Roche to increase global supply, with Roche primarily responsible for development and distribution outside the U.S.
Details of the Agreement
Regeneron expects to begin delivering the additional REGEN-COV doses to the U.S. government in September, with the vast majority delivered in Q4 2021. Regeneron will record all net sales associated with this agreement. Pursuant to a prior agreement, Roche will manufacture approximately one third of the doses for Regeneron to fulfill this new agreement with the U.S. government.
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.
Multiple analyses have shown that the antibody cocktail retains potency against the main variants of concern circulating within the U.S., including Delta (first identified in India), Gamma (first identified in Brazil), Beta (first identified in South Africa) and Mu (first identified in Colombia), with information available in the Fact Sheet for Healthcare Providers. Consequently, REGEN-COV remains available for use across the U.S., and Regeneron will continue actively monitoring the potency of REGEN-COV against emerging variants.
REGEN-COV has not been approved by the FDA, but is currently authorized for treatment and post-exposure prophylaxis in certain high risk individuals. 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 or 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. This authorization is for the duration of the declaration that circumstances exist justifying the authorization of the emergency uses under section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner. Additional information about REGEN-COV in the U.S. is below (authorized uses and important safety information).
In August, Regeneron submitted the first of two Biologics License Applications (BLAs) for REGEN-COV. The initial submission included data on the efficacy and safety of REGEN-COV to treat and prevent SARS-CoV-2 infection in non-hospitalized people. The second BLA submission will focus on those hospitalized because of COVID-19, and is expected to be completed later this year.
Emergency or temporary pandemic use authorizations are currently in place in more than 35 countries, including the U.S., several European Union countries, India, Switzerland and Canada, and the antibody cocktail is fully approved in Japan.
Regeneron and Roche 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 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-COV (casirivimab and imdevimab), Dupixent (dupilumab), Libtayo (cemiplimab-rwlc), Praluent (alirocumab), Kevzara (sarilumab), Evkeeza (evinacumab-dgnb) and Inmazeb (atoltivimab, maftivimab and odesivimab-ebgn).
U.S. 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:
- 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
Limitations of Authorized Use (Post-Exposure Prophylaxis)
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 CDC website (https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant-cases.html) as well as information from state and local health authorities regarding reports of viral variants of importance in their region to guide treatment decisions
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
Date: Sep 14, 2021
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