REGEN-COV Antibody (Casirivimab and Imdevimab) Description
Regeneron's REGEN-COV Antibody Cocktail is a combination of 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.
Regeneron 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.
DrugBank: DB15691; KEGG D11938, D11939
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. 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 October 28, 2020, the company announced 'positive, prospective results from an ongoing Phase 2/3 seamless trial in the COVID-19 outpatient setting showing its investigational antibody cocktail met the primary and key secondary endpoints.
In the overall patient population (n=799), patients were prospectively characterized before treatment by serology tests to see if they had already generated antiviral antibodies on their own and were thus classified as seronegative (no measurable antiviral antibodies) or seropositive (measurable antiviral antibodies).
Approximately 38% of patients were seropositive, 51% were seronegative, and 11% were categorized as "other" due to unclear or unknown serology status. Approximately 50% of patients were Hispanic, 9% were African American, and 60.5% had one or more underlying risk factors for severe COVID-19, including obesity (37%). On average, patients were 42.2 years of age. In total, 47% of participants were male, and 53% were female.
The Phase 3 portion of this trial continues in non-hospitalized patients. COVID-19 Antibody Cocktail is also being studied in a Phase 2/3 clinical trial to treat COVID-19 in hospitalized patients, the Phase 3 open-label RECOVERY trial of hospitalized patients in the UK, and a Phase 3 trial for the prevention of COVID-19 in household contacts of infected individuals.'
On December 17, 2020, David Weinreich, M.D., Senior Vice President and Head of Global Clinical Development at Regeneron, said in a press release: "The peer-reviewed NEJM publication of our first set of clinical data in recently infected COVID-19 patients showed 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. The investigational cocktail is now available to indicated high-risk U.S. patients under an Emergency Use Authorization, and we also continue a robust clinical development program."
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.
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.
Regeneron (REGN) is a leading biotechnology company that invents life-transforming medicines for people with serious diseases.
REGEN-COV Antibody (Casirivimab and Imdevimab) Indication
The COVID-19 Antibody Cocktail Casirivimab and imdevimab are investigational therapies authorized by the 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. 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.
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 in 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
REGEN-COV is currently authorized and available in a 2,400 mg IV dose, with infusion times as short as 20 minutes.
REGEN-COV Antibody (Casirivimab and Imdevimab) News
May 5, 2021 - Roche India received emergency use authorization of the Central Drugs Standards Control Organisation for antibody cocktail (Casirivimab and Imdevimab) that is indicated for the treatment of 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 the results of 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.
March 19, 2021 - The U.S. FDA published a revised EUA Fact Sheet.
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 for use in 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 is producing 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. 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 that the current hospitalized patient trial be modified.
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. 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 initiation of 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
Clinical Trial NCT04381936: Phase 2/3 Randomised Evaluation of COVID-19 Therapy (RECOVERY) with 15,000 participants. Estimated Primary Completion Date: December 2021.
Clinical Trial NCT04519437: Phase 1 Study Assessing the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Repeated Subcutaneous Doses of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies (REGN10933+REGN10987) in Adult Volunteers as Related to COVID-19.
Clinical Trial NCT04425629: Phase 1/2 Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Ambulatory Adult Patients With COVID-19. Last Update Posted: December 16, 2020.
Clinical Trial NCT04426695: A Phase 1/2 Master Protocol Assessing the Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Hospitalized Patients With COVID-19 Last Update Posted: February 4, 2021. Estimated study completion date: April 16, 2021
Clinical Trial NCT04452318: Phase 3 COVID-19 Study Assessing the Efficacy and Safety of Anti-Spike SARS CoV-2 Monoclonal Antibodies for Prevention of SARS CoV-2 Infection Asymptomatic in Healthy Adults and Adolescents Who Are Household Contacts to an Individual With a Positive SARS-CoV-2 RT-PCR Assay. Last Update Posted: January 25, 2021. Estimated study completion date: August 15, 2021.
Clinical Trial NCT04666441: Phase 2 COVID-19 Study Assessing the Virologic Efficacy of REGN10933+REGN10987 Across Different Dose Regimens in Adult Outpatients With SARS-CoV-2 Infection. Last Update Posted: March 16, 2021. Estimated study completion date: August 13, 2021.