REGEN-COV Antibody (Casirivimab and Imdevimab) Description
Regeneron's REGEN-COV Antibody Cocktail (Ronapreve) combines monoclonal antibodies casirivimab and imdevimab, explicitly designed to block the infectivity of SARS-CoV-2, the coronavirus that causes COVID-19. This was the first antibody therapy to demonstrate an anti-viral effect in patients hospitalized with COVID-19.
Regeneron's core technologies allow for the rapid and efficient generation of these protective anti-viral antibodies outside of the body, derived from genetically humanized mice or convalescent humans. The resulting antibodies correspond to the most potent anti-viral antibodies that could be elicited by a vaccine or through exposure to a pathogen.
These REGEN-COV antibodies can be delivered to people via injection, providing "passive immunity" and immediately protecting the disease. However, they must be re-administered to remain effective over time. These antibodies can also treat an existing infection, unlike vaccines, which can only be used preventatively.
Regeneron's potent, virus-neutralizing antibodies that form the REGEN-COV Antibody 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, published on August 21, 2020. DrugBank: DB15691; KEGG D11938, D11939
On May 17, 2021, Regeneron announced data from a phase 3 study found 'patients treated with REGEN-COV had 4-day shorter duration of symptoms and significantly reduced viral load than placebo.'
Regeneron's VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies.
On June 25, 2021, the Assistant Secretary for Preparedness and Response (ASPR) issued a notice saying 'REGEN-COV and sotrovimab are monoclonal antibody therapies currently authorized for the same use bamlanivimab and etesevimab administered together. Based on similar in vitro assay data currently available, REGEN-COV and sotrovimab are likely to retain activity against the P.1 or B.1.351 variants. Therefore, all treatment delivery sites can continue ordering REGEN-COV from the authorized distributor by following the existing ordering and reporting procedures. All treatment sites may also find information on the availability and ordering of sotrovimab by visiting GlaxoSmithKline’s website at www.sotrovimab.com.
Japan's Ministry of Health, Labour, and Welfare Approved Regeneron's REGEB-COV (casirivimab and imdevimab) antibody cocktail to treat patients with mild to moderate COVID-19 on July 20, 2021.
Regeneron Pharmaceuticals, Inc. is collaborating with Roche to increase the global supply of REGEN-COV. Regeneron is responsible for developing and distributing the treatment in the U.S., and Roche is primarily responsible for development and distribution outside the U.S.
REGEN-COV Antibody (Casirivimab and Imdevimab) History
The concept that drug cocktails can prevent viral escape has previously been demonstrated for traditional antiviral drugs used to treat HIV and other viruses. However, Regeneron now reports the fundamental realization that this can also be true for antibody-based therapies, as reported in a paper published in Science on August 21, 2020, entitled "Antibody Cocktail to SARS-Cov-2 Spike Protein Prevents Rapid Mutational Escape Seen with Individual Antibodies," which further defines the protective value of the multiple-antibody approach against SARS-CoV-2 specifically.
Regeneron scientists evaluated thousands of fully human antibodies produced by the company's proprietary VelocImmune® mice, which have been genetically modified to have a human immune system, as well as antibodies isolated from humans who have recovered from COVID-19.
Regeneron has recently partnered with Roche on August 19, 2020, to increase COVID-19 Antibody Cocktail's global supply. If COVID-19 Antibody Cocktail proves safe and effective in clinical trials and regulatory approvals are granted, Regeneron will manufacture and distribute it in the U.S., and Roche will develop, manufacture, and distribute it outside the USA.
On October 7, 2020, the company issued a 'Statement on REGN-COV2 Emergency Use Authorization Request: After our discussions with regulatory authorities, we have submitted a request to the U.S. Food and Drug Administration for an Emergency Use Authorization (EUA) for our COVID-19 Antibody Cocktail investigational antibody combination for COVID-19. Under our agreement with the U.S. government for the initial doses of COVID-19 Antibody Cocktail, if a EUA is granted, the government has committed to making these doses available to the American people at no cost and would be responsible for their distribution. At this time, there are doses available for approximately 50,000 patients, and we expect to have doses available for 300,000 patients in total within the next few months.'
On December 29, 2020, the company announced 'the Phase 3 program in hospitalized patients to continue based on passing futility analysis on the ability to reduce the incidence of death or mechanical ventilation. As in an earlier outpatient trial, immune status when patients entered the trial was a strong predictor of viral load and clinical outcomes.' "In this trial, patients who had not yet mounted their own immune response had much higher viral loads and much worse clinical outcomes; for example, in the placebo group, seronegative patients were almost three times more likely to die compared to seropositive patients," stated George D. Yancopoulos, M.D., Ph.D., President, and Chief Scientific Officer at Regeneron.
This COVID-19 Antibody Cocktail's development and manufacturing has been funded in part with federal funds from the Biomedical Advanced Research and Development Authority under OT number: HHSO100201700020C.
New York-based Regeneron (REGN) is a leading biotechnology company that invents life-transforming medicines for people with serious diseases.
REGEN-COV Antibody (Casirivimab and Imdevimab) Variant Effectiveness
On May 26, 2021, the U.S. CDC announced that the combined frequency of the P.1 variant (Brazil) and the B.1.351 variant (South Africa) now exceeds 10% in Arizona, California, Florida, Indiana, Oregon, and Washington. REGEN-COV is an alternative monoclonal antibody therapy currently authorized for the same use as bamlanivimab and etesevimab administered together. Based on similarities in vitro assay data currently available, REGEN-COV is likely to retain activity against the P.1 and B.1.351 variants. The U.S. FDA recommends that health care providers in Arizona, California, Florida, Indiana, Oregon, and Washington use this alternative authorized monoclonal antibody therapy until further notice.
REGEN-COV Antibody (Casirivimab and Imdevimab) Indication
The COVID-19 Antibody Cocktail Casirivimab and imdevimab (Ronapreve) are investigational therapies authorized by the U.S. FDA for emergency use. Casirivimab and imdevimab are not FDA Approved for any use. The safety and effectiveness of casirivimab and imdevimab have not been fully established to treat COVID-19.
Casirivimab and imdevimab administered together are authorized for the treatment of 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.
Regeneron’s outpatient trial's clinical evidence suggests that monoclonal antibodies such as casirivimab and imdevimab have the greatest benefit when given early after diagnosis. However, in In the U.S., other than clinical trials, casirivimab and imdevimab are not authorized for use in patients who are hospitalized or require oxygen therapy due to COVID-19, or for people currently using chronic oxygen therapy because of underlying comorbidity who require an increase in baseline oxygen flow rate due to COVID-19, says the company.
In the USA, REGEN-COV is not authorized for use in hospitalized patients due to COVID-19 or requires oxygen therapy or for people currently using chronic oxygen therapy because of underlying comorbidity requiring an increase in baseline oxygen flow rate COVID-19.
REGEN-COV Antibody (Casirivimab and Imdevimab) Indication For Women
Pregnancy: There is currently limited clinical experience using casirivimab and imdevimab injection in COVID-19 patients who are pregnant. Casirivimab and imdevimab injection therapy should be used during pregnancy only if the potential benefit justifies the mother and fetus's potential risk. Nursing Mothers: There is currently no clinical experience using casirivimab and imdevimab injection in COVID-19 patients breastfeeding. The development and health benefits of breastfeeding should be considered along with the mother's clinical need for casirivimab and imdevimab injection and any potential adverse effects on the breastfed child from casirivimab imdevimab injection or the underlying maternal condition.
REGEN-COV Antibody (Casirivimab and Imdevimab) Dosage
On June 3, 2021, the U.S. Food and Drug Administration updated the Emergency Use Authorization for REGEN-COV (Ronapreve), lowering the dose to 1,200 mg (600 mg casirivimab and 600 mg imdevimab) is half the dose originally authorized. As part of the updated EUA, REGEN-COV should be administered by intravenous infusion; subcutaneous injections are an alternative when IV infusion is not feasible and would lead to a delay in treatment.
Healthcare providers should review the Fact Sheet for Healthcare Providers for information on the authorized use of REGEN-COV and mandatory requirements of the EUA and comply with the requirements of the EUA.
In the U.S., REGEN-COV can be administered by intravenous infusion (as short as 20 minutes) or by subcutaneous injection (4 injections), which is an alternative when the intravenous infusion is not feasible and would lead to a delay in treatment. In addition, it is now authorized as a co-formulated single vial or in individual vials to be administered together.
DRUG: Casirivimab; Imdevimab
REGEN-COV Antibody (Casirivimab and Imdevimab) News
July 20, 2021 - Japan Approved Regeneron's casirivimab and imdevimab antibody cocktail (Ronapreve) to treat patients with mild to moderate COVID-19. This Approval is the first time the antibody cocktail has received full Approval to treat COVID-19.
June 16, 2021 - Regeneron Pharmaceuticals, Inc. confirmed positive results from the largest trial assessing any monoclonal antibody treatment in patients hospitalized with severe COVID-19. The UK RECOVERY trial found that adding investigational REGEN-COV™ to usual care reduced the risk of death by 20% in patients who had not mounted a natural antibody response on their own against SARS-CoV-2, compared to usual care on its own.
June 9, 2021 - Canada Health Authorized By Interim Order (249830) Casirivimab and imdevimab for use concerning the COVID-19 pandemic, per section 5 of the Interim Order Respecting the Importation, Sale, and Advertising of Drugs for Use concerning COVID-19.
June 4, 2021 - Regeneron Pharmaceuticals, Inc. announced the U.S. Food and Drug Administration (FDA) updated the Emergency Use Authorization (EUA) for REGEN-COV™, lowering the dose to 1,200 mg (600 mg casirivimab and 600 mg imdevimab), which is half the dose originally authorized. As part of the updated EUA, REGEN-COV should be administered by intravenous infusion; subcutaneous injections are an alternative when IV infusion is not feasible and would lead to a delay in treatment. REGEN-COV has not been Approved by FDA but has been Authorized for emergency use.
June 4, 2021 - The U.S. government will purchase all REGEN-COV doses delivered by June 30, 2021, and may accept additional doses through September 30, 2021, at its discretion, up to a maximum amount of 1.25 million doses. Regeneron expects to deliver at least 1 million REGEN-COV doses to the U.S. government in the 2Q'21.
June 3, 2021 - The U.S. FDA issued a letter that stated: 'having concluded that revising this EUA is appropriate to protect the public health or safety under section 564(g)(2) of the Act, FDA is reissuing the February 25, 2021 letter in its entirety, authorizing revisions to the authorized use6 for REGEN-COV, a change in dosing of REGEN-COV from 2400 mg (1200 mg casirivimab and 1200 mg imdevimab) to 1200 mg (600 mg casirivimab and 600 mg imdevimab), and the addition of a new presentation consisting of a single vial containing casirivimab and imdevimab co-formulated in a 1:1 ratio for either intravenous infusion or subcutaneous injection. New conditions have been incorporated on the provision of samples of the authorized REGEN-COV to the U.S. Department of Health and Human Services upon request and the submission of certain genomic sequencing and virology information to the FDA by a specified date.'
May 26, 2021 - The U.S. HHS issued a Public Health Emergency saying 'REGEN-COV is likely to retain activity against the P.1 and B.1.351 variants. The U.S. FDA recommends that health care providers in Arizona, California, Florida, Indiana, Oregon, and Washington use this alternative authorized monoclonal antibody therapy until further notice.
May 5, 2021 - Roche India received emergency use authorization of the Central Drugs Standards Control Organisation for antibody cocktail (Casirivimab and Imdevimab) to treat mild to moderate COVID-19.
May 3, 2021 - Regeneron announced that positive Phase 3 data from trials evaluating two Regeneron medicines will be featured at the 2021 American Thoracic Society International Conference in the Breaking News: Clinical Trial Results in Pulmonary Medicine Scientific Symposium on May 17, 2021.
April 12, 2021 - Regeneron Pharmaceuticals, Inc. announced positive data from a Phase 3 trial (2069B) of recently infected asymptomatic COVID-19 patients, evaluating REGEN-COV™ (casirivimab with imdevimab) 1,200 mg administered via subcutaneous administration. REGEN-COV reduced the overall risk of progressing to symptomatic COVID-19 by 31% (primary endpoint) and by 76% after the third day. The trial also demonstrated that REGEN-COV shortened symptom duration and markedly reduced viral levels.
April 9, 2021 - Regeneron Pharmaceuticals, Inc. announced that the newly updated National Institutes of Health (NIH) COVID-19 Treatment Guidelines strongly recommend that REGEN-COV™ (casirivimab with imdevimab) be used in non-hospitalized COVID-19 patients ("outpatients") at high risk of clinical progression. The NIH Category 'AIIa' is a 'strong' rating based on randomized trials.
March 23, 2021 - Regeneron announced phase 2 and 3 results for their anti-body cocktail. REGEN-COV in high-risk non-hospitalized COVID-19 patients met its primary endpoint, showing the investigational REGEN-COV (casirivimab with imdevimab) significantly reduced the risk of hospitalization or death by 70% compared to placebo. Additionally, REGEN-COV significantly shortened the duration of symptoms by 4 days. The phase 2 dose-ranging showed significant and comparable viral reductions for all REGEN-COV doses tested, including as low as 300 mg.
February 4, 2021 - The European Medicine Agency (EMA) announced the human medicines committee is reviewing available data on the use of the monoclonal antibodies casirivimab, imdevimab, bamlanivimab, and etesevimab to treat patients with COVID-19 who do not require oxygen supplementation and who are at high risk of progressing to severe COVID-19.
February 1, 2021 - The European Medicines Agency (EMA) announced the human medicines committee (CHMP) had started a ‘rolling review’ of data of the medicine known as REGN-COV2 antibody combination (casirivimab / imdevimab), which is being co-developed by Regeneron Pharmaceuticals, Inc. and F. Hoffman-La Roche, Ltd (Roche) for the treatment and prevention of COVID-19.
January 26, 2021 - Regeneron Pharmaceuticals, Inc. announced positive initial results from an ongoing Phase 3 clinical trial evaluating REGEN-COV™ (casirivimab and imdevimab antibody cocktail) used as a passive vaccine for the prevention of COVID-19 in people at high risk of infection (due to household exposure to a COVID-19 patient). Passive vaccination with REGEN-COV resulted in 100% prevention of symptomatic infection (8/223 placebo vs. 0/186 REGEN-COV) and approximately 50% lower overall rates of infection (symptomatic and asymptomatic) (23/223 placebo vs. 10/186 REGEN-COV).
January 22, 2021 - Local media reported Regeneron is confident that its popular antibody cocktail is still highly effective. That's because the Regeneron cocktail, which is not a vaccine but was designed to treat people who have already been infected with the coronavirus, is a mix of two different antibodies that fight COVID-19 instead of just one.
January 21, 2021 - The NEJM published an ORIGINAL ARTICLE - REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19. In this interim analysis, the REGN-COV2 antibody cocktail reduced viral load, with a greater effect in patients whose immune response had not yet been initiated or who had a high viral load at baseline.
January 12, 2021 - Regeneron Pharmaceuticals announced that the U.S. Department of Health and Human Services and the Department of Defense would purchase an additional supply of the casirivimab and imdevimab antibody cocktail non-hospitalized COVID-19 patients to meet the federal government's Operation Warp Speed goals.
December 29, 2020 - Regeneron Pharmaceuticals, Inc. announced encouraging initial data from an ongoing Phase 1/2/3 clinical trial of the Regeneron antibody cocktail, casirivimab and imdevimab, in hospitalized COVID-19 patients requiring low-flow oxygen. Under an agreement with the U.S. government, Regeneron produces approximately 300,000 doses (2,400 mg) for outpatient use under the EUA.
December 17, 2020 - The NEJM published a study that found 'In this interim analysis, the REGN-COV2 antibody cocktail reduced viral load, with a greater effect in patients whose immune response had not yet been initiated or who had a high viral load at baseline. In addition, safety outcomes were similar in the combined REGN-COV2 dose groups and the placebo group.'
November 21, 2020 - The U.S. Food and Drug Administration issued an emergency use authorization (EUA) for casirivimab and imdevimab to be administered together for the treatment of mild to moderate COVID-19 in adults and pediatric patients (12 years of age or older weighing at least 40 kilograms with positive results of direct SARS-CoV-2 viral testing and who are at high risk for progressing to severe COVID-19. This includes 65 years of age or older or certain chronic medical conditions.
November 5, 2020 - Regeneron announced an update from the independent data monitoring committee (DMC) for the United Kingdom-based RECOVERY trial evaluating REGN-COV2 in hospitalized patients with COVID-19. The DMC reviewed available safety and efficacy data for the 15,545 total patients randomized, including the 325 patients in the arm randomized to receive either REGN-COV2 or control.
October 30, 2020 - Regeneron announced it received a recommendation from the independent data monitoring committee for the REGN-COV2 antibody cocktail treatment trials for COVID-19 to modify the current hospitalized patient trial.
October 28, 2020 - Regeneron Pharmaceuticals, Inc. announced positive, prospective results from an ongoing Phase 2/3 seamless trial in the COVID-19 outpatient setting showing its investigational antibody cocktail, REGN-COV2, met the primary and key secondary endpoints. In addition, REGN-COV2 significantly reduced viral load and patient medical visits.
October 8, 2020 - Study: REGN-COV2 antibodies prevent and treat SARS-CoV-2 infection in rhesus macaques and hamsters.
October 7, 2020 - The Company issued a 'Statement on REGN-COV2 Emergency Use Authorization Request.'
October 2, 2020 - Regeneron Pharmaceuticals, Inc. confirmed that the company provided a single 8-gram dose of REGNCOV2, a cocktail of two monoclonal antibodies, for US President Trump. REGN-COV2 is an investigational COVID-19 therapy provided in response to an Individual Patient Investigational New Drug application, commonly known as ‘compassionate use’ request, from the President’s physicians.
September 29, 2020 - Regeneron Pharmaceuticals, Inc. announced the first data from a descriptive analysis of a seamless Phase 1/2/3 trial of its investigational antibody cocktail REGN-COV2 showing it reduced viral load and the time to alleviate symptoms in non-hospitalized patients with COVID-19.
August 3, 2020 - Non-peer-reviewed study: REGN-COV2 antibody cocktail prevents and treats SARS-CoV-2 infection in rhesus macaques and hamsters.
July 6, 2020 - Regeneron Pharmaceuticals, Inc. announced the initiation of a Phase 3 trial to evaluate REGN-COV2's ability to prevent infection among uninfected people who have had close exposure to a COVID-19 patient (such as the patient's housemate) and is being run jointly with the National Institute of Allergy and Infectious Diseases. REGN-COV2 has also moved into the Phase 2/3 portion of two adaptive Phase 1/2/3 trials testing the cocktail's ability to treat hospitalized and non-hospitalized patients with COVID-19.
June 11, 2020 - Regeneron announced the first clinical trial of REGN-COV2, its investigational dual antibody cocktail to prevent and treat COVID-19.
REGEN-COV Antibody (Casirivimab and Imdevimab) Clinical Trials
REGEN-COV continues to be studied to Assess the Safety, Tolerability, Pharmacokinetics, and Immunogenicity against COVID-19.