Regen-CoV for preventing hospitalization and death in COVID-19

Scientists at Regeneron Pharmaceuticals have developed two antibodies that attack different parts of SARS-CoV-2. The combination of antibodies is called Regen-CoV. It is important that they are used in combination, as this minimizes the chance of SARS-CoV-2 developing the ability to resist their effects. Modifications have been made to the Regen-CoV antibodies so that they persist in circulation when infused. The antibodies are:

• casirivimab
• imdevimab

In experiments with hamsters and monkeys, Regen-CoV can significantly reduce the amount of SARS-CoV-2 in the lungs of infected animals. The antibodies also reduce complications from this viral infection. They are effective against the ancestral strain of SARS-CoV-2 that first appeared in 2019 as well as key variants of concern.

In people

Regen-CoV has been tested in a placebo-controlled study with 4,567 people who were diagnosed with COVID-19. All participants were not sufficiently ill to be hospitalized but were considered at high risk for becoming severely ill with COVID-19. Treatment consisted of a single dose of each antibody given intravenously on the same day. The study assessed the effect of a combined dose of 1,200 mg (600 mg of each antibody) vs. a combined dose of 2,400 mg (1,200 mg of each antibody) vs. placebo. The antibody combination reduced the risk of hospitalization and death by about 70%, regardless of which dose was used.

All participants in the study had at least one risk factor associated with an increased risk of severe COVID-19. These risk factors included the following:

• obesity – 58%
• age greater than 50 years – 51%
• cardiovascular disease – 36%

Results

Regardless of the dose used, the antibodies reduced the time to resolution of symptoms by four days vs. placebo. The total duration of symptoms was as follows:

• Regen-CoV – 10 days
• placebo – 14 days

There were seven deaths in the study, distributed as follows:

• 1,200-mg dose group – one person
• 2,400-mg dose group – one person
• placebo group – five people

Regeneron has not released detailed information about the safety of the antibodies used in this study but stated that “serious adverse events were largely related to COVID-19” and were distributed as follows:

• 1,200-mg dose group – 1.1%
• 2,400-mg dose group – 1.3%
• placebo group – 4%

In a different study of Regen-CoV, doctors tested the effects of different doses and formulation of the antibodies in about 800 non-hospitalized people with COVID-19:

• intravenous doses – 2,400 mg, 1,200 mg, 600 mg, 300 mg, placebo
• injection just under the skin (subcutaneous injection) – 1,200 mg, 600 mg, placebo

The company stated that all doses of the antibody reduced the amount of SARS-CoV-2 in participants compared to placebo.

Subcutaneous doses are easier to administer than intravenous doses. Regeneron plans to discuss the effects of this study with regulatory authorities to find out if they will approve the subcutaneous dosing of the antibodies.

Other trials of Regen-CoV testing the antibodies in people hospitalized with COVID-19 are underway.

—Sean R. Hosein

REFERENCES:

1. Regeneron. Phase 3 Trial Shows REGEN-COV (casirivimab with imdevimab) antibody cocktail reduced hospitalization or death by 70% in non-hospitalized COVID-19 patients. Press release. 23 March 2021.
2. Baum A, Ajithdoss D, Copin R, et al. Regen-COV2 antibodies prevent and treat SARS-CoV-2 infection in rhesus macaques and hamsters. Science. 2020 Nov 27;370(6520):1110-1115.
3. Baum A, Fulton BO, Wloga E, et al. Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science. 2020 Aug 21;369(6506):1014-1018.
4. Copin R, Baum A, Wloga E, et al. In vitro and in vivo preclinical studies predict Regen-CoV protection against emergence of viral escape in humans. bioRxiv. 2021. DOI: 10.1101/2021.03.10.434834. [preprint].