Effectiveness of sotrovimab demonstrated in patients with mild to moderate COVID-19

The unprecedented COVID-19 pandemic has claimed more than 5 million lives globally since it emerged in Wuhan, China, in late December 2019. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily affects the respiratory system, but serious symptoms have also been noted in other organ systems. Patients suffering from chronic diseases like diabetes, chronic kidney disease, and chronic obstructive pulmonary disease, and the elderly are more prone to hospitalization due to severe COVID-19.

Due to transformations in the spike protein of SARS-CoV-2 since the pandemic, several variants have emerged that increase the seriousness and communicability of the disease and reduce the effectiveness of treatment and preventative measures used worldwide.

A particular variant of concern evolved in India, the Delta variant, which has amplified transmissibility and is capable of eluding vaccine-induced immunity. Thus there is a pressing need for effective treatment against such existing variants of concern as well as variants that may emerge in the future.

Sotrovimab, a human monoclonal antibody isolated during the SARS outbreak in 2003, has proven its ability to neutralize SARS-CoV-2. It targets a specific region in the SARS-CoV-2 spike protein, which does not compete with angiotensin-converting enzyme 2 (ACE2) binding.

Assessing the safety and effectiveness of sotrovimab in patients with mild to moderate COVID-19

In an attempt to study the safety and effectiveness of sotrovimab in more vulnerable patients suffering from mild to moderate symptoms of COVID-19, a multinational team of researchers conducted the COVID-19 Monoclonal antibody Efficacy Trial-Intent to Care Early (COMET-ICE) trial. It was a randomized, placebo-controlled, double-blind, multicenter, phase 3 study, with primary, secondary, exploratory, and safety outcomes. This study is published on the medRxiv* preprint server.

The primary outcome was disease progression in terms of the percentage of patients hospitalized due to any reason for 24 hours or more or death by day 29.

Secondary outcomes included the percentage of patients who visited the emergency room, were hospitalized for any period, or death as well as the number of patients developing severe COVID-19 requiring supplemental oxygen.

Exploratory outcomes included the duration of hospital, intensive care unit, or ventilator stay through day 29. Lastly, safety outcomes included all adverse events such as hospitalization and deaths irrespective of COVID-19-related or not.

Study outcomes

Of 1,351 patients screened from August 2020 through March 2021, sotrovimab or placebo was randomly given to 1,057 patients. The primary outcome results showed a 79% reduction in hospitalization due to any reason for over 24 hours or death with sotrovimab treatment.

Secondary outcome results demonstrated a decline of emergency room visits for any reason, hospitalization for any period or death by 66% with sotrovimab.

Additionally, treatment with sotrovimab reduced respiratory complications due to COVID-19 by 74% and decreased the requirement for oxygen and ventilator.

“Treatment with sotrovimab reduced the progression of COVID-19 in high-risk patients with mild to moderate disease.”

Limitations

There were a few limitations in this phase 3 study. Since only a small number of events were reported in patients with sotrovimab for the primary and secondary outcomes, it was challenging to identify the features of patients or diseases related to COVID-19 development in patients treated with sotrovimab.

Also, the limited size of the study population was a barrier to the detection of unusual adverse events. Finally, since the study enrolled patients for only a limited time period of six months, the long-term effect of sotrovimab on variants of concern was not clear.

Inferences from the study

Although mass vaccination campaigns are ongoing in many countries, a large percentage of the global population is still unvaccinated because they are immunocompromised or due to vaccine hesitancy. Therefore, an alternative is required to reduce hospitalization and deaths due to COVID-19.

The outcome of the COMET-ICE trial showed that sotrovimab reduced the advancement of COVID-19 in vulnerable patients suffering from minor to moderate symptoms. In addition, sotrovimab treatment led to a decrease in the rate of hospitalization and demand for oxygen and improvement in COVID-19 symptoms.

The authors believe that sotrovimab is highly effective and well-tolerated with no safety concerns among patients who are more prone to the complications of COVID-19.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.