Tuesday, 28 September, 2021
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FDA expands emergency use of REGEN-COVTM (casirivimab and imdevimab)

Regeneron Pharmaceuticals has announced that the US Food and Drug Administration (FDA) has updated the Emergency Use Authorisation (EUA) for the investigational COVID-19 antibody cocktail REGEN-COVTM (casirivimab and imdevimab).

The authorisation now includes post-exposure prophylaxis in people at high risk for progression to severe COVID-19, who are not fully vaccinated or are not expected to mount an adequate response to vaccination, and have been exposed to a SARS-CoV-2 infected individual, or who are at high risk of exposure to an infected individual because of infection occurring in the same institutional setting (such as in nursing homes or prisons).

In those who require repeat dosing for ongoing exposure, REGEN-COV can also now be administered monthly. This new indication in people aged 12 and older is in addition to the previously granted authorisation to treat non-hospitalised patients. REGEN-COV is not a substitute for vaccination against COVID-19, and is not authorised for pre-exposure prophylaxis to prevent COVID-19.

"The FDA authorisation enables certain people at high risk of developing severe COVID-19 infection to access REGEN-COV if they have been exposed to the virus – the first time an antibody treatment has been authorised for this purpose," said Dr George D. Yancopoulos, president and chief scientific officer of Regeneron.

"With this authorisation, the FDA highlights the needs of immune-compromised people, including those taking immune-suppressive medicines, who may not mount an adequate response to vaccination, who are exposed to a person with COVID-19 or are in an institutional setting and are at high risk of exposure because of infection occurring in the same setting. Expanding the use of REGEN-COV in post-exposure settings is a very helpful step, and we continue to work with the FDA as it undertakes its review of REGEN-COV in a broader group of people, including in a pre-exposure prophylactic setting for those who are immune-compromised, and in patients hospitalised due to COVID-19."

Experts estimate that some three percent of the US population may not respond fully to COVID-19 vaccination because of immune-compromising conditions or immune-suppressive medicines. This includes people receiving chemotherapy, or with haematologic cancers like chronic lymphocytic leukaemia, people receiving stem cells or haemodialysis, those who have had organ transplants, and/or people taking certain medications that might blunt immune response (e.g., mycophenolate, rituximab, azathioprine, anti-CD20 monoclonal antibodies, Bruton tyrosine kinase inhibitors). This authorisation enables these groups to use REGEN-COV to prevent infection in post-exposure and certain institutional settings.

Under the EUA for post-exposure prophylaxis, REGEN-COV can be administered by subcutaneous injection or intravenous infusion. For people who aren't expected to mount an adequate immune response to vaccination and who have an ongoing exposure to SARS-CoV-2 for more than four weeks, the initial 1,200mg dose can be followed by subsequent repeat dosing of REGEN-COV 600mg once every four weeks, for the duration of ongoing exposure.

REGEN-COV has not been approved by the FDA, but is currently authorised for the duration of the declaration that circumstances exist justifying the authorisation of the emergency use under section 564(b)(1) of the Act, 21 USC § 360bbb-3(b)(1), unless the authorisation is terminated or revoked sooner.

Multiple analyses have shown that REGEN-COV retains potency against the main variants of concern circulating within the US, including Delta (B.1.617.2; first identified in India), Gamma (P.1; first identified in Brazil) and Beta (B.1.351; first identified in South Africa). Consequently, REGEN-COV remains available for use across the US, and Regeneron will continue actively monitoring the potency of REGEN-COV against emerging variants.

Regeneron is collaborating with Roche to increase global supply of the antibody cocktail, with Roche primarily responsible for development and distribution outside the US. Regeneron and Roche 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.

About the clinical data supporting the EUA extension

The REGEN-COV EUA for post-exposure prophylaxis is based on data from multiple groups.

A pivotal Phase 3 trial jointly run with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), assessed REGEN-COV for post-exposure prophylaxis of COVID-19 in household contacts of individuals infected with SARS-CoV-2 (index case). REGEN-COV was found to reduce the risk of symptomatic infections by 81% in those who were not infected when they entered the trial (p<0.0001).

There were 1,505 participants (753 REGEN-COV, 752 placebo) who were not infected (seronegative with a negative PCR test) when they entered the trial.
In a post-hoc analysis in the subgroup of participants who met the criteria for high risk for progression to severe COVID-19 (570 REGEN-COV, 567 placebo), there was a 76% risk reduction in COVID-19 with REGEN-COV treatment compared to placebo (p<0.0001).

Adverse events were reported in 20% (265/1,311) of REGEN- COV participants and 29% (379/1,306) of placebo participants. Injection site reactions (all mild to moderate) occurred in 4% (55) of REGEN-COV participants and 2% (19) of placebo participants. Hypersensitivity reactions occurred in 0.2% (2) of REGEN-COV participants, all of which were mild in severity. It also reduced the risk of symptomatic infections by 62% in a broader group of asymptomatic participants, regardless of infection status, based on a post-hoc analysis (p<0.0001).

There were 2,378 participants who were asymptomatic when they entered the trial, regardless of serology (1,201 REGEN-COV, 1,177 placebo).
 Adverse events for uninfected individuals are reported above, and for infected individuals (n=311) were reported in 34% (52/155) of REGEN-COV participants and 48% (75/156) of placebo participants. Injection site reactions (all mild to moderate) occurred in 4% (6) of REGEN-COV participants and 1% (1) of placebo participants. There were no cases of hypersensitivity reaction.

An additional double-blind, placebo-controlled Phase 1 trial evaluated the safety, pharmacokinetic and immunogenicity of repeated doses of REGEN-COV 1,200mg (n=729) compared with placebo (n=240), administered subcutaneously in healthy adults every four weeks for 24 weeks.

During the 28-day assessment period, adverse events were reported in 52% (380) of REGEN-COV participants and 46% (111) of placebo participants. Injection site reactions occurred in 12% and 4% of participants following a single dose of REGEN-COV and placebo, respectively; and with repeat dosing injection site reactions occurred in 35% (252) of REGEN-COV participants and 16% (38) of placebo participants. Hypersensitivity reactions occurred in 1% (8) of REGEN-COV participants, all of which were mild to moderate.

About the REGEN-COV antibody cocktail

REGEN-COV (casirivimab and imdevimab) is a cocktail of two monoclonal antibodies 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-neutralising 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.

Issued by Regeneron Pharmaceuticals

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