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REGEN-COV™ (casirivimab and imdevimab) Phase 3 RECOVERY Trial Meets Primary Outcome, Improving Survival in Hospitalized COVID-19 Patients Lacking an Immune Response to SARS-CoV-2

TARRYTOWN, N.Y. June 16, 2021 /PRNewswire/ --

Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today welcomed 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.

"These results are very exciting. The hope was that by giving a combination of antibodies targeting the SARS-CoV-2 virus we would be able to reduce the worst manifestations of COVID-19," said Sir Peter Horby, Professor of Emerging Infectious Diseases in the Nuffield Department of Medicine, University of Oxford, and Joint Chief Investigator for the RECOVERY trial. "There was, however, great uncertainty about the value of antiviral therapies in late-stage COVID-19 disease. It is wonderful to learn that even in advanced COVID-19 disease, targeting the virus can reduce mortality in patients who have failed to mount an antibody response of their own."

RECOVERY is the first trial large enough to definitively determine whether REGEN-COV reduces mortality in patients hospitalized with severe COVID-19. Previous Phase 3 trials in non-hospitalized COVID-19 patients have shown that REGEN-COV reduced viral levels, shortened the time to resolution of symptoms and significantly reduced the risk of hospitalization or death. In a Phase 1/2 trial in hospitalized patients, REGEN-COV also rapidly reduced viral levels, with preliminary evidence suggesting that it lowered the risk of death or receiving mechanical ventilation, with the benefit driven by patients who entered the trial without having mounted a natural antibody response of their own (seronegative); and in the absence of REGEN-COV treatment, seronegative patients had higher mortality rates than patients who had already mounted their own immune response (seropositive).

Based on the above Phase 1/2 data, the independently-run RECOVERY trial prospectively focused on seronegative patients. Similar to the prior trial, patients in RECOVERY who received usual care alone had double the mortality rate at day 28 if they were seronegative (30%) compared to seropositive (15%); approximately one-third of hospitalized patients were seronegative (n=3,153), one-half were seropositive (n=5,272) and one-sixth had unknown serostatus (n=1,360). The mean age of patients for this comparison was 62 years, and more than 90% received corticosteroids across all groups.

The primary outcome of RECOVERY showed that adding REGEN-COV 8,000 mg to usual care reduced all-cause mortality by 20% in seronegative patients (primary analysis population), compared to usual care alone (24% of patients in the REGEN-COV group died versus 30% in the usual care group by day 28; rate ratio [RR]: 0.80; 95% confidence interval [CI]: 0.70-0.91; p=0.001). When combining the larger seropositive group (as well as those with unknown status) with the seronegative patients, there was no longer a significant effect on 28-day mortality (overall 20% of patients in the REGEN-COV group died, versus 21% in the usual care group; RR: 0.96; 95% CI: 0.86-1.03; p=0.17).

"Definitive Phase 3 trials have now demonstrated that REGEN-COV can alter the course of COVID-19 infection from prevention, to very early infection, all the way through to when patients are on a ventilator in the hospital," said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron. "We are incredibly grateful to the RECOVERY team, participating investigators and patients for conducting this in-depth analysis, and hope that the results mean that even more patients may soon be able to benefit from this life-saving medicine. We intend to rapidly discuss these results with regulatory authorities, including in the U.S. where we will ask for our EUA to be expanded to include appropriate hospitalized patients."

Among seronegative patients in the RECOVERY trial, the median duration of hospital stay was 4 days shorter in the REGEN-COV group (13 days versus 17 days), and the proportion of patients discharged alive by day 28 was greater (64% versus 58%; RR: 1.19; 95% CI: 1.08-1.30). Among the seronegative patients not on invasive mechanical ventilation at baseline, the risk of progressing to the composite endpoint of invasive mechanical ventilation or death was lower among the REGEN-COV group than the usual care group (30% versus 37%; RR: 0.83; 95% CI: 0.75-0.92). No such benefits were seen in the overall trial population (combining patients with negative, positive, or unknown serostatus).

"The RECOVERY trial has shown that in patients who had not made their own antibodies against SARS-CoV-2, treating them with REGEN-COV antibodies dramatically reduced their risk of dying or being on a ventilator, and also shortened how many days they remained in the hospital," said David Weinreich, M.D., Executive Vice President, Global Clinical Development at Regeneron. "The trial was conducted at a time when most patients had not been fully vaccinated. These results provide hope to patients who have a poor immune response to either the vaccine or natural infection, as well as those who are exposed to variants for whom their existing antibodies might be sub-optimal."

Multiple analyses, including a recent publication in Cell, have shown that REGEN-COV retains potency against the main variants of concern circulating within the U.S.; consequently, REGEN-COV remains available for use in all 50 states. REGEN-COV retains potency against variants including P.1 (first identified in Brazil, now classified by the World Health Organization [WHO] as Gamma), B.1.351 (first identified in South Africa, now classified by the WHO as Beta) and B.1.162.2 (first identified in India, now classified by the WHO as Delta). The combined frequency of the P.1 and B.1.351 variants now exceeds 10% of new COVID-19 diagnoses across eight states (Arizona, California, Florida, Illinois, Indiana, Massachusetts, Oregon and Washington), and the prevalence of these and other variants continues to be closely monitored.

Today's data in hospitalized patients follow multiple positive Phase 3 results earlier this year from Regeneron-sponsored trials assessing the ability of REGEN-COV to treat outpatients already infected with SARS-COV-2 (including symptomatic outpatients and recently infected asymptomatic patients), and also to prevent infection in close contacts of infected individuals. REGEN-COV has not been approved by the U.S. Food and Drug Administration (FDA), but is currently authorized in the U.S. under an Emergency Use Authorization (EUA) to treat mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing ≥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. This use is 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.

Regeneron is in discussions with the FDA to expand the current EUA to other populations, including the prevention and hospitalized patient settings. Later this summer, Regeneron expects to submit a full Biologics License Application (BLA) for REGEN-COV.

Regeneron is collaborating with Roche to increase global supply of REGEN-COV. Regeneron is responsible for development and distribution of the treatment in the U.S., and Roche is primarily responsible for development and distribution outside the U.S. The companies 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.

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 U.S. Department of Health and Human Services' Office of the Assistant Secretary for Preparedness and Response, under OT number: HHSO100201700020C.

About the Trial
The RECOVERY trial (Randomised Evaluation of COVid-19 thERapY) was conducted by the registered clinical trials units in the Nuffield Department of Population Health in partnership with the Nuffield Department of Medicine. The trial was supported by a grant to the University of Oxford from UK Research and Innovation/National Institute for Health Research (NIHR) and by core funding provided by NIHR Oxford Biomedical Research Centre, Wellcome, the Bill and Melinda Gates Foundation, the Department for International Development, Health Data Research UK, the Medical Research Council Population Health Research Unit and NIHR Clinical Trials Unit Support Funding.

Between September 18, 2020 and May 22, 2021, 9,785 patients hospitalized with COVID-19 were randomly allocated to receive usual care plus REGEN-COV (8,000 mg by intravenous infusion) or usual care alone as part of the RECOVERY trial. Usual care was determined by individual facilities and clinicians, and could include steroids and remdesivir. Follow-up is complete for 99% of participants.

The trial involved many thousands of doctors, nurses, pharmacists, and research administrators at 176 hospitals across the whole of the UK, supported by staff at the NIHR Clinical Research Network, NHS DigiTrials, Public Health England, Department of Health & Social Care, the Intensive Care National Audit & Research Centre, Public Health Scotland, the Secure Anonymised Information Linkage at University of Swansea, and the NHS in England, Scotland, Wales and Northern Ireland.

About the REGEN-COV Antibody Cocktail
REGEN-COV (casirivimab and imdevimab) is a cocktail of two monoclonal antibodies (also known as REGN10933 and REGN10987) 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 Science.

Under an EUA, REGEN-COV is available throughout the U.S. – information on availability in your area is available from the Department of Health and Human Services and the National Infusion Center Association. REGEN-COV can be administered by intravenous infusion (as short as 20 minutes) or by subcutaneous injection (four injections), which is an alternative when intravenous infusion is not feasible and would lead to a delay in treatment. It is now authorized as a co-formulated single vial, or in individual vials to be administered together.

In the U.S., REGEN-COV is not authorized 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.

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 USE AND IMPORTANT SAFETY INFORMATION
REGEN-COV, (casirivimab and imdevimab) co-formulated product and REGEN-COV (casirivimab and imdevimab) supplied as individual vials to be administered together, 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. [see Limitations of Authorized Use]

Limitations of Authorized Use

REGEN-COV (casirivimab and imdevimab) is not authorized for use in patients:

Benefit of treatment with REGEN-COV has not been observed in patients hospitalized due to 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

Definition of High Risk Patients
The following medical conditions or other factors may place adults and pediatric patients (age 12-17 years and weighing at least 40 kg) at higher risk for progression to severe COVID-19:

For additional information on medical conditions and factors associated with increased risk for progression to severe COVID, see the CDC website: https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html. Healthcare providers should consider the benefit-risk for an individual patient.

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

Warnings and Precautions:

Adverse Reactions:

Patient Monitoring Recommendations: Clinically monitor patients during infusion and observe patients for at least 1 hour after intravenous infusion or subcutaneous dosing is complete

Use in Specific Populations:

About Regeneron

Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents life-transforming medicines for people with serious diseases. Founded and led for over 30 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to nine FDA-approved treatments and numerous product candidates in development, almost all of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, pain, hematologic conditions, infectious diseases and rare diseases.

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 (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 (collectively, "Regeneron's Product Candidates") and research and clinical programs now underway or planned, including without limitation the development program relating to the REGEN-COVTM (casirivimab and imdevimab) antibody cocktail; how long the Emergency Use Authorization ("EUA") granted by the U.S. Food and Drug Administration (the "FDA") for REGEN-COV will remain in effect and whether the EUA is revoked by the FDA based on its determination that the underlying health emergency no longer exists or warrants such authorization or other reasons; 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 Application planned to be filed with the FDA and referenced in this press release) and new indications for Regeneron's Products; uncertainty of the utilization, market acceptance, and commercial success of Regeneron's Products and Regeneron's Product Candidates, including the impact of recommendations, guidelines, or studies (whether conducted by Regeneron or others and whether mandated or voluntary) on any of the foregoing or any potential regulatory approval of Regeneron's Products and Regeneron's Product Candidates (such as REGEN-COV); whether the EUA for REGEN-COV will be expanded for use for appropriate hospitalized patients (based on the results of the UK RECOVERY trial discussed in this press release or otherwise) and/or in the prevention setting; the ability of Regeneron's collaborators, suppliers, or other third parties (as applicable) to perform manufacturing, filling, finishing, packaging, labeling, distribution, and other steps related to Regeneron's Products and Regeneron's Product Candidates (including REGEN-COV) and the impact of the foregoing on Regeneron's ability to supply Regeneron's Products and Regeneron's Product Candidates (including REGEN-COV); the ability of Regeneron to manage supply chains for multiple products and product candidates; safety issues resulting from the administration of Regeneron's Products and Regeneron's Product Candidates (such as REGEN-COV) in patients, including serious complications or side effects in connection with the use of Regeneron's Products and Regeneron's Product Candidates in clinical trials; determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron's ability to continue to develop or commercialize Regeneron's Products and Regeneron's Product Candidates, including without limitation REGEN-COV; ongoing regulatory obligations and oversight impacting Regeneron's Products, research and clinical programs, and business, including those relating to patient privacy; the availability and extent of reimbursement of Regeneron's Products from third-party payers, including private payer healthcare and insurance programs, health maintenance organizations, pharmacy benefit management companies, and government programs such as Medicare and Medicaid; coverage and reimbursement determinations by such payers and new policies and procedures adopted by such payers; competing drugs and product candidates that may be superior to, or more cost effective than, Regeneron's Products and Regeneron's Product Candidates; the extent to which the results from the research and development programs conducted by Regeneron and/or its collaborators may be replicated in other studies and/or lead to advancement of product candidates to clinical trials, therapeutic applications, or regulatory approval; unanticipated expenses; the costs of developing, producing, and selling products; the ability of Regeneron to meet any of its financial projections or guidance and changes to the assumptions underlying those projections or guidance; the potential for any license, collaboration, or supply agreement, including Regeneron's agreements with Sanofi, Bayer, and Teva Pharmaceutical Industries Ltd. (or their respective affiliated companies, as applicable), as well as Regeneron's collaboration with Roche relating to the casirivimab and imdevimab antibody cocktail (known as REGEN-COV in the United States), to be cancelled or terminated; and risks associated with intellectual property of other parties and pending or future litigation relating thereto (including without limitation the patent litigation and other related proceedings relating to EYLEA® (aflibercept) Injection, Dupixent® (dupilumab), Praluent® (alirocumab), and REGEN-COV), other litigation and other proceedings and government investigations relating to the Company and/or its operations, the ultimate outcome of any such proceedings and investigations, and the impact any of the foregoing may have on Regeneron's business, prospects, operating results, and financial condition. A more complete description of these and other material risks can be found in Regeneron's filings with the U.S. Securities and Exchange Commission, including its Form 10-K for the year ended December 31, 2020 and its Form 10-Q for the quarterly period ended March 31, 2021. Any forward-looking statements are made based on management's current beliefs and judgment, and the reader is cautioned not to rely on any forward-looking statements made by Regeneron. Regeneron does not undertake any obligation to update (publicly or otherwise) any forward-looking statement, including without limitation any financial projection or guidance, whether as a result of new information, future events, or otherwise.

Regeneron uses its media and investor relations website and social media outlets to publish important information about the Company, including information that may be deemed material to investors. Financial and other information about Regeneron is routinely posted and is accessible on Regeneron's media and investor relations website (http://newsroom.regeneron.com) and its Twitter feed (http://twitter.com/regeneron).

SOURCE Regeneron Pharmaceuticals, Inc.

Posted: June 2021

REGEN-COV (casirivimab and imdevimab) FDA Approval History

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