New England Journal of Medicine Publishes Positive Initial Regeneron Antibody Cocktail Results in Non-hospitalized Patients with COVID-19
"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," said
"Building on these initial findings, we were gratified to recently report follow-on data from the next-stage analysis of this ongoing trial, which prospectively replicated these results in a rigorous and statistically significant manner. These follow-on data provided the first definitive prospective evidence demonstrating anti-viral activity for a treatment regimen now available for COVID-19, and also further documented the ability of this treatment to decrease the need for further medical attention," said
Regeneron previously announced the initial results featured in this NEJM publication from the Phase 1/2 portion of the trial that enrolled 275 patients randomized 1:1:1 to receive 8 grams casirivimab and imdevimab (high-dose, n=90), 2.4 grams casirivimab and imdevimab (low-dose, n=92) or placebo (n=93). Approximately 56% of patients were Latino/Hispanic, 13% were Black/
Regeneron also subsequently announced additional prospective results in a total of 799 patients from the trial. In both the initial descriptive analyses of 275 patients, as well as in the following prospective analyses involving a total of 799 patients, a greater effect was observed in patients treated with the antibody cocktail who did not have SARS-CoV-2 antibodies at baseline ('sero-antibody-negative') or who had high viral load at baseline. As would be expected, a much higher proportion of sero-antibody-negative patients had high viral loads when they entered the trial. Additionally, a smaller proportion of antibody cocktail-treated patients required medically-attended visits due to COVID-19 (inclusive of hospitalizations, urgent care or emergency room visits, in-person physician or telemedicine visits) through day 29 compared to placebo; there was an even greater benefit on this endpoint among sero-antibody-negative patients.
In the initial 275 patients, rates of adverse events (AEs) were similar among groups. Serious AEs occurred in 2 placebo patients, 1 low-dose patient and 0 high-dose patients. AEs included infusion-related reactions (1 placebo patient, 0 low-dose patients, 2 high-dose patients) and hypersensitivity reactions (2 placebo patients, 0 low-dose patients, 1 high-dose patient).
About casirivimab and imdevimab
Casirivimab and imdevimab (formerly known as REGN-COV2 or REGEN-COV2) is a cocktail of two monoclonal antibodies (also known as REGN10933 and REGN10987, respectively) and was designed specifically to block infectivity of SARS-CoV-2, the virus that causes COVID-19.
To develop this novel medicine, Regeneron scientists evaluated thousands of fully-human antibodies produced by the company's VelocImmune® mice, which have been genetically modified to have a human immune system, as well as antibodies identified from humans who have recovered from COVID-19. 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.
The development and manufacturing of the antibody cocktail has been funded in part with federal funds from BARDA under OT number: HHSO100201700020C. Data from the Phase 1/2/3 clinical trial supported an Emergency Use Authorization for casirivimab and imdevimab administered together, granted by the
AUTHORIZED USE AND IMPORTANT SAFETY INFORMATION
Authorized Emergency Use
Casirivimab and imdevimab injection is an investigational combination therapy and has been authorized by FDA for the emergency use described above. Casirivimab and imdevimab injection is not FDA approved for any use. Safety and effectiveness of casirivimab and imdevimab injection have not yet been established for the treatment of COVID-19.
This authorized use is 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.
Limitations of Authorized Use
- Casirivimab and imdevimab injection 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.
- Benefit of treatment with casirivimab and imdevimab injection has not been observed in patients hospitalized due to COVID-19. Monoclonal antibodies, such as casirivimab and imdevimab, may be associated with worse clinical outcomes when administered to hospitalized patients requiring high flow oxygen or mechanical ventilation with COVID-19.
Definition of High-Risk Patients
High-risk is defined as patients who meet at least one of the following criteria:
- Have a body mass index (BMI) ≥35
- Have chronic kidney disease
- Have diabetes
- Have immunosuppressive disease
- Are currently receiving immunosuppressive treatment
- Are ≥65 years of age
- Are ≥55 years of age AND have
- cardiovascular disease, OR
- hypertension, OR
- chronic obstructive pulmonary disease/other chronic respiratory disease.
- Are 12 – 17 years of age AND have
- BMI ≥85th percentile for their age and gender based on
CDCgrowth charts, OR
- sickle cell disease, OR
- congenital or acquired heart disease, OR
- neurodevelopmental disorders, for example, cerebral palsy, OR
- a medical-related technological dependence, for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19), OR
- asthma, reactive airway or other chronic respiratory disease that requires daily medication for control.
- BMI ≥85th percentile for their age and gender based on
Warnings and Precautions:
- Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions: There is a potential for serious hypersensitivity reaction, including anaphylaxis, with administration of casirivimab and imdevimab injection. If signs or symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive therapy. Infusion-related reactions have been observed with administration of casirivimab and imdevimab injection. Signs and symptoms of infusion related reactions may include fever, chills, nausea, headache, bronchospasm, hypotension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, and/or dizziness. If an infusion-related reaction occurs, consider slowing or stopping the infusion and administer appropriate medications and/or supportive care.
- Limitations of Benefit and Potential for Risk in Patients with Severe COVID-19: Benefit of treatment with casirivimab and imdevimab injection has not been observed in patients hospitalized due to COVID-19. Monoclonal antibodies, such as casirivimab and imdevimab, may be associated with worse clinical outcomes when administered to hospitalized patients requiring high flow oxygen or mechanical ventilation with COVID-19. Therefore, casirivimab and imdevimab injection is not authorized for use in 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.
- Serious adverse events (SAEs) were reported in 4 (1.6%) patients in the casirivimab and imdevimab injection 2,400 mg group, 2 (0.8%) patients in casirivimab and imdevimab injection 8,000 mg group and 6 (2.3%) patients in the placebo group. None of the SAEs were considered to be related to study drug. SAEs that were reported as Grade 3 or 4 adverse events were pneumonia, hyperglycemia, nausea and vomiting (2,400 mg casirivimab and imdevimab injection), intestinal obstruction and dyspnea (8,000 mg casirivimab and imdevimab injection) and COVID-19, pneumonia and hypoxia (placebo). Casirivimab and imdevimab injection are not authorized at the 8,000 mg dose (4,000 mg casirivimab and 4,000 mg imdevimab).
Casirivimab and imdevimab are not authorized at the 8,000 mg dose (4,000 mg casirivimab and 4,000 mg imdevimab).
- One anaphylactic reaction was reported in the clinical program. The event began within 1 hour of completion of the infusion, and required treatment including epinephrine. The event resolved. Infusion-related reactions, of grade 2 or higher severity, were reported in 4 subjects (1.5%) in the 8,000 mg (4,000 mg casirivimab and 4,000 mg imdevimab) arm. These infusion-related reactions events were moderate in severity; and include pyrexia, chills, urticaria, pruritus, abdominal pain, and flushing. One infusion-related reaction (nausea) was reported in the placebo arm and none were reported in the 2,400 mg (1,200 mg casirivimab and 1,200 mg imdevimab) arm. In two subjects receiving the 8,000 mg dose of casirivimab and imdevimab, the infusion-related reactions (urticaria, pruritus, flushing, pyrexia, shortness of breath, chest tightness, nausea, vomiting) resulted in permanent discontinuation of the infusion. All events resolved.
Patient Monitoring Recommendations: Clinically monitor patients during infusion and observe patients for at least 1 hour after infusion is complete.
Use in Specific Populations:
- Pregnancy: There is currently limited clinical experience in the use of 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 potential risk for the mother and the fetus.
- Nursing Mothers: There is currently no clinical experience in use of casirivimab and imdevimab injection in COVID-19 patients who are 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 and imdevimab injection or from the underlying maternal condition.
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.
Regeneron 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 (including those discussed in this press release), 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 and research and clinical programs now underway or planned, including without limitation the development program relating to casirivimab and imdevimab (Regeneron's investigational multi-antibody therapy for the treatment and prevention of COVID-19); how long the Emergency Use Authorization ("EUA") granted by the
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