FDA ACCEPTS REGEN-COV (CASIRIVIMAB AND IMDEVIMAB) FOR PRIORITY REVIEW FOR TREATMENT AND PROPHYLAXIS OF COVID-19
Regeneron?Pharmaceuticals, Inc.?(NASDAQ:?REGN) today?announced that the?U.S. Food and Drug Administration?(FDA) has accepted for priority review a Biologics License Application (BLA) for REGEN-COV??(casirivimab and imdevimab) to treat COVID-19 in non-hospitalized patients and as prophylaxis in certain individuals. The FDA has assigned a target action date of?April 13, 2022?and informed us that they currently are planning to hold an advisory committee meeting to discuss this application in advance of that date.
The BLA is supported by two positive Phase 3 trials involving more than 6,000 patients that evaluated the efficacy and safety of REGEN-COV to treat?non-hospitalized?patients already infected with SARS-CoV-2, and to prevent symptomatic infection in asymptomatic household contacts of SARS-CoV-2 infected individuals (both?uninfected?and?infected?contacts). A second BLA submission focusing on the treatment of patients hospitalized due to COVID-19 is expected to be submitted later this year.
Regulatory submissions are also progressing in the?European Union?(EU). Earlier this week, the?European Medicines Agency?(EMA)?accepted?for review the Marketing Authorization Application for the same antibody cocktail, known as Ronapreve? in the EU and other countries outside of the?U.S., for use in certain people either as a treatment in infected non-hospitalized patients, or as prophylaxis. The submission approach for the EMA is similar to that used for the FDA, with a?Type II Variation?planned in those already hospitalized because of?COVID-19.
In the?U.S., REGEN-COV has not been approved by the FDA, but is currently?authorized?under an Emergency Use Authorization (EUA) to?treat people with mild to moderate COVID-19 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. REGEN-COV is available for free to?eligible people?as part of a?U.S.?government funded program, and in September Regeneron?announced?a new agreement with the?U.S.?government to supply an additional 1.4 million 1,200 mg doses of REGEN-COV by?January 2022. Information on how to access REGEN-COV throughout the?U.S.?is available from the?Department of Health and Human Services?and the?National Infusion Center Association.
The development and manufacturing of REGEN-COV have been funded in part with federal funds from the?Biomedical Advanced Research and Development Authority, 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 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, 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. 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 emergency use for the 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).
REGEN-COV is an investigational medicine that has emergency or temporary pandemic authorizations currently in place in more than?40?countries, including the?U.S., several countries in the EU,?India,?Switzerland?and?Canada, and?the antibody cocktail?is?fully approved in?Japan?and conditionally approved in the?UK.
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.?Regeneron and Roche share a commitment to making the antibody cocktail available 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).
AUTHORIZED USES AND IMPORTANT SAFETY INFORMATION
Treatment:
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
- 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)
- 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
- Contraindication: 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
- 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
- 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
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