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VIR-7831 (sotrovimab) – preventing hospitalization and death in COVID-19

There are many potential medicines in development for the prevention and treatment of COVID-19. One group of potential therapies is called monoclonal antibodies.

About antibodies

Antibodies are proteins made by the immune system. These proteins help the immune system recognize a particular germ and mark it for destruction by the immune system.

Monoclonal antibodies are made in the lab. These antibodies are designed by scientists to attack a specific germ—in this case, SARS-CoV-2.

About a year ago, two companies—Vir Biotechnology and GlaxoSmithKline (GSK)—began cooperating on the development of potential interventions to prevent and treat COVID-19.

The companies have developed the following antibodies

  • VIR-7831, also known as GSK-4182136
  • VIR-7832, also known as GSK-4182137

Preliminary results from a placebo-controlled trial of VIR-7831 have found that this antibody is highly effective (85%) at reducing the risk of hospitalization or death from COVID-19.

The Comet-Ice study

In a study called Comet-Ice, researchers recruited adults with mild or moderate COVID-19 who were at high risk for hospitalization and randomly assigned them to receive one of the following intravenous interventions:

  • 500 mg of VIR-7831
  • placebo

An interim analysis from 583 participants (291 who received the antibody and 292 who received placebo) found that there was an 85% reduction in the risk of hospitalization or death in people who received the antibody. Due to this effect of the antibody, the independent data monitoring committee that oversaw the study recommended that enrollment be halted. The trial will continue to monitor participants for an additional 24 weeks.

VIR-7831 has been found to be generally safe in the Comet-Ice study. Further details from this study will be released in the future.

Vir and GSK plan to test other formulations of VIR-7831 by giving it as an intramuscular injection. Large clinical trials are also planned to confirm the findings from Comet-Ice.

Some variants of concern

As mentioned previously in this issue of TreatmentUpdate, SARS-CoV-2 infects cells and forces them to produce copies of this virus. Small errors, or mutations, in the production of copies of SARS-CoV-2 occur from time to time. These mutations result in a slightly altered shape or structure of the virus. Over many cycles of infection, as the virus passes from one person to another, mutations accumulate. Mutations that confer an advantage to the virus tend to be carried forward in future copies of the virus. Mutant viruses that can increase harm in some way—such as causing infection more easily, evading vaccine-induced protection and antibody-based therapies—are called variants of concern (VOC).

Some VOC include the following:

  • B.1.1.7 – first identified in the UK in December 2020
  • B.1.351 – initially reported in South Africa in December 2020
  • P1 – has 35 mutations and was initially reported in Brazil in January 2021

These variants, particularly B.1.1.7, are spreading and have been reported in many countries including Canada.

Lab experiments with VIR-7831 and VIR-7832 and cells infected with variants of concern have found that these antibodies are highly effective against variants of concern B.1.1.7, B.1.351 and P.1. Not only do they stop the virus from spreading in cultures of cells in the lab, they also attract cells of the immune system to help capture and destroy SARS-CoV-2-infected cells. These properties of the VIR antibodies should not be surprising. They were developed based on an antibody that was highly effective against SARS-CoV-1, the virus that caused an outbreak of SARS in 2002. As SARS-CoV-1 is closely related in shape to SARS-CoV-2, the VIR antibodies have the ability to neutralize key variants of concern. VIR-7831 has also been optimized to remain in circulation longer than most antibodies. As well, it is supposed to accumulate in the lungs and airways—places that SARS-CoV-2 tends to infect.

Harmful antibodies

In the case of infection with certain viruses (such as Dengue virus, HIV and Zika virus), the immune system produces antibodies that quickly lose their potency and/or are generally unhelpful in containing infection. In some cases, antibodies produced by the immune system against these viruses may even help the viruses infect cells. However, VIR-7831 and VIR-7832 do not cause this problem in laboratory experiments.

Hamsters

The Middle Eastern hamster (also called the golden or Syrian hamster) is an important animal model to study SARS-CoV-2 infection. These animals tend to experience severe disease when they are infected with SARS-CoV-2. Experiments with these hamsters confirm that VIR-7831 (no data was made available about the other antibody) was able to reduce levels of SARS-CoV-2.

For the future

In the months ahead, Vir and GSK are seeking approval for VIR-7831 from regulatory authorities in the U.S., Canada and Europe while continuing to conduct further studies.

—Sean R. Hosein

REFERENCES:

  1. Pinto D, Park YJ, Beltramello M, et al. Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Nature. 2020 Jul;583(7815):290-295.
  2. McCallum M, De Marco A, Lempp FA, et al. N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2. Cell. 2021; in press.
  3. GlaxoSmithKline and Vir Biotechnology. Vir Biotechnology and GSK announce VIR-7831 reduces hospitalization and risk of death in early treatment of adults with COVID-19. Press release. 21 March 2021.
  4. Cathcart AL, Havenar-Daughton C, Lempp FA, et al. The dual function monoclonal antibodies VIR-7831 and VIR-7832 demonstrate potent in vitro and in vivo activity against SARS-CoV-2. bioRxiv 2021.03.09.434607 [Preprint].
  5. Zhou D, Dejnirattisai W, Supasa P, et al. Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera. Cell. 2021; in press.
  6. Garcia-Beltran WF, Lam EC, St Denis K, et al. Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity. Cell. 2021; in press.