Sotrovimab in early COVID-19

Sotrovimab is a powerful antibody that attacks SARS-CoV-2 (the virus that causes COVID-19) and is meant to be used in the early stages of COVID-19 infection. Sotrovimab is available in Canada, the U.S. and some other countries.

Sotrovimab has been tested in a large randomized clinical trial called Comet-Ice. This study analyzed data from 291 people who were given sotrovimab and 292 people who were given placebo. All participants had early-stage COVID-19 and were not hospitalized at the time they entered the study.

Researchers found that sotrovimab significantly reduced (by 85%) the chance of participants requiring hospitalization for more than 24 hours or dying. No participant given sotrovimab required admittance to an intensive care unit or died. Sotrovimab was generally well tolerated with rates of adverse events similar to those seen in people who took placebo.

Researchers overseeing Comet-Ice halted further recruitment to the study because the drug was highly effective.

Study details

Researchers recruited participants from the following countries:

• Brazil
• Canada
• Spain
• United States

All participants had been diagnosed with SARS-CoV-2 infection several days prior to entering the study. All had mild-to-moderate symptoms of COVID-19.

The researchers stated that participants were considered at “high risk” for worsening symptoms of COVID-19 because of underlying conditions and/or their age (55 years and older). Researchers recruited participants between late August 2020 and early March 2021.

Participants were randomly assigned to receive one of the following intravenous interventions over the course of one hour:

• sotrovimab 500 mg
• placebo

The average profile of participants at the time they entered the study is as follows:

• age – 53 years (the proportion who were aged 65 and older was 22%; the proportion older than 70 years was 11%)
• 54% women, 46% men
• major ethno-racial groups: White – 87%; Hispanic – 63%; Black – 7%; Asian – 6% (numbers do not total 100 due to overlap of categories)
• major underlying conditions/and older age: age 55 and older – 47%; obesity – 63%; diabetes requiring medication – 23%; moderate-to-severe asthma – 16%
• common symptoms of COVID-19 – cough, muscle ache or soreness, headache, fatigue

Results

Participants who received sotrovimab were 85% less likely to require hospitalization that lasted more than 24 hours compared to participants on placebo. The distribution of participants was as follows:

• sotrovimab – 1% (3 people) required hospitalization
• placebo – 7% (21 people) required hospitalization

Short periods of hospitalization (less than 24 hours) are consistent with people going to the emergency room because of possible unstable underlying conditions. Many well-designed studies of treatments for COVID-19 focus on prolonged periods of hospitalization because those can be associated with worsening symptoms of COVID-19.

The hospitalizations that occurred in Comet-Ice were generally associated with worsening symptoms of COVID-19. The one exception was a person who had a history of intestinal obstruction prior to the study. This person required hospitalization 22 days after an infusion of sotrovimab because they developed another bout of intestinal obstruction.

In the intensive care unit

Five participants required admission to an intensive care unit, all of whom received placebo. Two of these five people were given invasive mechanical ventilation. A third person required invasive mechanical ventilation but declined this intervention and died 29 days after entering the study.

Safety

During a clinical trial, participants can develop adverse events. These require investigation to determine whether they are caused by the underlying disease process, the study drug(s) or something unrelated to the study.

The proportions of participants with adverse events were distributed as follows:

• sotrovimab – 17%
• placebo – 19%

COVID-19 is a relatively new and scary disease, so participants and their doctors were likely hypervigilant about reporting any symptoms that occurred during the study. Most adverse events that occurred in Comet-Ice were due to COVID-19. Furthermore, the distribution of adverse events that were serious was greater in people who received placebo:

• sotrovimab – 2%
• placebo – 6%

This result is not surprising, as more people who were on placebo would have become sicker over time and therefore reported more adverse effects.

One adverse effect—diarrhea—was more common in people who received sotrovimab:

• sotrovimab – 1% (6 people) reported diarrhea
• placebo – less than 1% (3 people) reported diarrhea

The diarrhea was mostly graded as mild.

Very rare side effects

The Canadian product monograph for sotrovimab states that one hospitalized person who received the drug developed anaphylaxis. Doctors injected the person with epinephrine and the person recovered. Note that sotrovimab is not meant to be used in hospitalized people with COVID-19.

Sotrovimab is derived from an antibody found in a survivor of SARS-CoV-1; this virus caused an outbreak of pneumonia almost 20 years ago. This antibody was only minimally modified into its present form (sotrovimab). It attacks a viral target. Due to these features, researchers do not expect sotrovimab to cause rare side effects.

About infusions in general

Antibody-based therapies are routinely used to treat many conditions, including arthritis, some forms of cancer, Crohn’s and colitis, and psoriasis. Doctors and nurses have found that reactions to infusions of these antibodies are relatively common but are generally mild to moderate in people with cancer and inflammatory conditions. General symptoms that can be associated with infusions of antibodies include the following:

• headache
• fatigue
• redness
• nausea
• fever
• pain

These symptoms usually resolve within hours to a day after infusion.

In very rare cases, more serious symptoms, such as anaphylaxis, can occur.

Sotrovimab and infusion-related reactions

The proportion of participants in Comet-Ice who developed infusion-related reactions were 1% among those who received sotrovimab and 1% in those who received placebo. These reactions appeared during or after infusion, were generally graded as mild and resolved within 24 hours. They included the following:

• fever
• chills
• dizziness
• rash
• itchy skin

One of the people who received sotrovimab had an infusion-related reaction of moderate intensity—shortness of breath.

Bear in mind

The data from Comet-Ice strongly suggest that sotrovimab can protect many people with mild-to-moderate COVID-19 from deteriorating. Sotrovimab was generally well tolerated.

For the future

Preliminary results from another clinical trial called Comet-Tail have been issued by GSK and ViiV through a press release. These preliminary results suggest that sotrovimab administered via intramuscular injection is not less effective than when given intravenously. The companies are planning or initiating discussions with regulatory authorities about authorizing intramuscular administration of sotrovimab in Canada, the European Union and the U.S.

—Sean R. Hosein

REFERENCES:

1. GlaxoSmithKline. Sotrovimab for injection. Product monograph. 14 September 2021.
2. Cathcart AL, Havenar-Daughton C, Lempp FL, et al. The dual function antibodies VIR-7831 and VIR-7832 demonstrate potent in vitro and in vivo activity against SARS-CoV-2. Preprint. 30 September 2021.
3. Gupta A, Gonzalez-Rojas Y, Juarez E, et al. Early treatment for Covid-19 with SARS-CoV-2 neutralizing antibody sotrovimab. New England Journal of Medicine. 2021; in press
4. Austin D. Why do placebos work? Scientists identify key brain pathway. Science. 27 October 2021.
5. GlaxoSmithKline. Primary endpoint met in COMET-TAIL Phase III trial evaluating intramuscular administration of sotrovimab for early treatment of COVID-19. Press release. 12 November, 2021.