September 23, 2021

Regeneron Welcomes World Health Organization Recommendation for Use of REGEN- COV™ (casirivimab and imdevimab) to Treat COVID-19

  • The WHO conditionally recommends REGEN-COV treatment for non-hospitalized high- risk patients and hospitalized patients who have not developed their own antibody response to the virus (seronegative)
  • REGEN-COVis the only monoclonal antibody therapy recommended by the WHO to treat the underlying SARS-CoV-2 infection that causes COVID-19
  • Regeneron has collaborated with Roche to increase global supply and ensure access outside of the U.S.; companies have been in discussions with the WHO and partners of the ACT Accelerator Initiative to support drug donations to low- and low-middle-income countries

Today the World Health Organization (WHO) updated its Therapeutics andCOVID-19:living guidelineto include the casirivimab and imdevimab monoclonal antibody cocktail, known as REGEN-COV™ in the U.S. and Ronapreve® in other countries. The guideline conditionally recommends REGEN-COV to treat high-risknon-hospitalized patients with non-severeCOVID-19 and seronegative (no measurable antiviral antibodies) hospitalized patients with severe or critical COVID-19.REGEN-COV is the only antibody therapy recommended by the WHO to treat the SARS-CoV-2 infection that causes COVID-19, and provides an important treatment option for patients at various stages of disease.

The WHO Guideline Development Group reviewed data from the robust REGEN-COV development program, which has reported positive Phase 3 trial results across the spectrum of COVID-19 infection, including the treatment of non-hospitalizedpatients already infected with SARS-CoV-2, and treatment of patients hospitalized due to COVID-19 infection, including the RECOVERY trial.

With robust clinical data and inclusion in treatment guidelines from various global public health organizations, demand for REGEN-COV has increased dramatically in recent months. Early on in the pandemic, Regeneron recognized the potential for this treatment to be widely needed and worked to ensure greater manufacturing capacity and equitable access. Manufacturing antibody medicines is incredibly complex and transferring the technology takes significant time, resources and skill. Only a limited number of facilities in the world have the capability to make medicines such as REGEN-COV in a safe and effective manner, and preserving the highest quality manufacturing standards is imperative to serving patients and maintaining their trust in our medicines.

Regeneron began collaborating with Roche last year to increase supply and ensure global access. Roche was selected for its ability to conduct technology transfer expeditiously and adhere to Regeneron's high product quality and safety standards, as well as for the large manufacturing capacity and global reach of their organization.

Under the agreement, Roche is primarily responsible for the development and distribution of REGEN-COV outside of the U.S., including pricing, and has utilized differential pricing to

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address affordability challenges in low-income countries (LICs) and middle-income countries. Both companies are committed to making REGEN-COV available to COVID-19 patients around the globe, and are in advanced discussions with partners of the Access to COVID-19 Tools (ACT) Accelerator Initiative, which includes the WHO, on making a donation of REGEN- COV for distribution in LICs and lower-middle-income countries (LMICs) to expedite access and to supplement pricing solutions in these countries.

REGEN-COV has emergency or temporary pandemic authorizations currently in place in more than 40 countries, with bilateral purchase agreements across many geographies and economies, including upper-middle income and LMICs. In addition, the companies have been working with the WHO to facilitate regulatory approvals in other LICs and LMICs.

In the U.S., REGEN-COV is available for free to eligible people, as part of a U.S. government funded program. Regeneron has worked to maximize production of REGEN-COV and recently announceda new agreement with the U.S. government to supply an additional 1.4 million 1,200 mg doses over the next four months. Information on how to access REGEN-COV throughout the U.S. is available from the Department of Health and Human Servicesand the National Infusion Center Association.

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 Celland 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. Regeneron will continue actively monitoring the potency of REGEN-COV against emerging variants.

In the U.S., REGEN-COV has not been approved by the Food and Drug Administration (FDA), but is currently authorizedto 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 prophylaxissettings. 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).

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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.

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-COVis not authorized for use in patients:
  1. who are hospitalized due to COVID-19, OR
  1. who require oxygen therapy due to COVID-19, OR
    1. 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

Post-Exposure Prophylaxis:

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
    o 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
    o 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)

Limitations of Authorized Use (Post-Exposure Prophylaxis)

  • Post-exposureprophylaxis with REGEN-COV is not a substitute for vaccination against COVID-19
  • REGEN-COVis not authorized for pre-exposure prophylaxis for prevention of COVID-19

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

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Healthcare providers should review the Fact Sheet for Healthcare Providersfor 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 Authorizationis available for reference, as well as the Dear Healthcare Provider Letterand 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

  • Contraindication:
    REGEN-COV is contraindicated in individuals with previous severe hypersensitivity reactions, including anaphylaxis, to REGEN-COV
  • Warnings and Precautions:
  1. Hypersensitivity Including Anaphylaxis and Infusion-RelatedReactions: 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-relatedreactions 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

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appropriate medications and/or supportive care if an infusion-related reaction occurs

  1. 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

    1. 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:
    1. 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

  1. COV-2069 (Post-exposureprophylaxis): 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

  1. 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

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Regeneron Pharmaceuticals Inc. published this content on 23 September 2021 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 24 September 2021 07:31:09 UTC.