Infectious Disease

FDA Approves AstraZeneca Antibody Cocktail For Pre-Exposure Prevention Of COVID-19

December 08, 2021

3 minutes read

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Kim reports on personal fees from Exagen Diagnostics and GlaxoSmithKline, as well as grants from the NIH and the Rheumatology Research Foundation.

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For the first time, the FDA has granted emergency approval for a long-acting monoclonal antibody cocktail for the prevention of symptomatic COVID-19 in adults and children 12 years and older.

According to data submitted to the FDA, Evusheld (tixagevimab plus cilgavimab), also known as AZD7442, from AstraZeneca may reduce the risk of symptomatic COVID-19 development in unvaccinated adults without prior SARS-CoV-2 infection by 77% compared to placebo reduce an increased risk of an inadequate immunization response.

COVID card 2_330832637

For the first time, the FDA has granted emergency approval to a long-acting monoclonal antibody cocktail for the prevention of symptomatic COVID-19 in adults. Source: Adobe Stock.

Alfred HJ Kim, MD, PhD, Assistant Professor of Medicine in the Department of Rheumatology at Washington University School of Medicine in St. Louis, Missouri, noted Wednesday’s approval marks a significant advance in protecting immunocompromised patients.

“This is really great news for the immunocompromised in general, but especially for those taking drugs that are at high risk of very poor or absent antibody responses,” Kim told Healio Rheumatology. “These patients now have an opportunity to receive protective antibodies. The timing is particularly good as the colder weather means the falls are on the rise – and the holidays are approaching. If it can be given before vacation dates, it offers additional protection for them. “

Alfred HJ Kim

According to Kim, the Evusheld EUA will have a particularly profound impact on patients receiving TNF inhibitors, as these individuals appear to be unable to neutralize the delta variant of the SARS-CoV-2 virus even if they are vaccinated . While COVID-19 booster vaccinations can address these concerns, they may not be an option for patients who have experienced side effects to the vaccine.

“This pre-exposure prophylaxis (PrEP) can neutralize Delta in these patients,” said Kim. “Given the number of people taking TNF inhibitors for rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and more, this could help provide additional protection that they don’t quite have right now. I should add that patients with TNF inhibitors who are given the booster dose may produce a response to Delta. However, if they responded to the vaccine, PrEP is a solid alternative. “

Kim added that he and his colleagues will now focus on giving their B-cell depleted patients, as well as those receiving mycophenolate, the newly available cocktail, as both populations are at risk of inadequately responding to COVID-19 vaccines .

The FDA’s EEA only approves the drug for adults and children aged 12 and over who weigh at least 40 kg who are not currently infected with SARS-CoV-2 and who have not recently been infected with COVID-19. Emergency clearance also requires individuals to have either a moderately to severely compromised immune system due to a medical condition or immunosuppressive medication or treatments that result in a potentially inadequate immune response to COVID-19 vaccination, or severe side effects to COVID-19 vaccination in a history of having -19 vaccine and / or components of vaccines.

Evusheld is not authorized for individuals to treat COVID-19 or prevent COVID-19 after exposure. The FDA also stressed that Evusheld is not a substitute for vaccination in those recommended to be vaccinated.

The FDA based its approval on data from the Phase 3 PROVENT study, which examined the efficacy and safety of Evusheld in 5,197 participants in 87 locations in the US, UK, Spain, France and Belgium. Participants were unvaccinated adults with no prior SARS-CoV-2 infection who were at increased risk of inadequate response to active immunization or an increased risk of COVID-19, including those whose location or circumstances increased their chances of infection.

According to AstraZeneca, at baseline, more than 75% of people who participated had comorbidities and other characteristics associated with an increased risk of severe COVID-19, including having an immunosuppressive illness or use of immunosuppressive drugs, diabetes, severe obesity, or heart disease , chronic obstructive pulmonary disease, and chronic kidney and liver disease.

Participants were randomized in a 2: 1 ratio to receive either a single intramuscular dose of 300 mg Evusheld or a placebo with saline solution given in two consecutive injections.

According to PROVENT researchers, Evusheld reduced the risk of symptomatic COVID-19 by 77% (95% CI, 46% to 90%) compared to placebo. None of the participants who received the monoclonal cocktail developed severe COVID-19 and none died. Meanwhile, three cases of severe COVID-19 have been recorded in the placebo arm, including two deaths. The study reported a total of 25 cases of symptomatic COVID-19 in both groups at the primary analysis.

In terms of safety, Evusheld was well tolerated, with preliminary analyzes showing balanced side effects between the placebo and treatment groups.

AstraZeneca’s application for an EEA also included data from the Phase 3 STORM CHASER study, which analyzed the efficacy and safety of more than 1,100 unvaccinated adults exposed to SARS-CoV-2 within the last 8 days. The study found that the cocktail reduced the risk of symptomatic COVID-19 compared to placebo by 33% (95% CI, -26% to 65%). However, this result was not significant and the study did not meet its primary endpoint.

Evusheld is a combination of two long-acting antibodies – tixagevimab (AZD8895) and cilgavimab (AZD1061) – obtained from B cells donated by convalescent patients after SARS-CoV-2 infection. It was discovered at Vanderbilt University Medical Center in Nashville with assistance from the U.S. Department of Health and Defense and licensed to AstraZeneca in June 2020.

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Leonard H. Calabrese, DO)

Leonard H. Calabrese, DO

The announcement of the EEA for Evusheld by AstraZeneca (tixagevimab is given together with cilgavimab) for pre-exposure prophylaxis (PrEP) of COVID-19 in certain adults with moderately to severely weakened immune systems due to a disease, immunosuppressive drugs or treatments and may not have an adequate immune response to the COVID Building -19 vaccination is good news for a large group of patients with immune-mediated inflammatory diseases (IMIDs), as well as other conditions such as cancer, transplants, and immunodeficiency.

A single intramuscular injection can provide protection for up to 6 months, practically on a par with an effective vaccination. The patients this is optimally designed for are precisely those who are least likely to build their own immune responses to the vaccines that have benefited so many in the general population. I’m especially happy for many patients who have done everything in their power to protect themselves – including vaccinations, mask-wearing, and social distancing – but are far more susceptible to severe COVID than the general vaccinated population. It’s a game changer for them.

There is much to be clarified in this EEA right now, especially where we will draw the line between the nearly 3% of the population who fall under this general category and currently deserve COVID-19 PrEP.

Leonard H. Calabrese, DO

Medical Editor-in-Chief, Healio Rheumatology

Professor of Medicine

Case Western Reserve University’s Cleveland Clinic Lerner College of Medicine

RJ Fasenmyer Chair of Clinical Immunology

Cleveland Clinic

Disclosure: Calabrese reports on advisory relationships with AbbVie, Centecor Biopharmaceutical, Crescendo Bioscience, GlaxoSmithKline, Horizon Pharma, Janssen Pharmaceuticals, Pfizer, Regeneron Pharmaceuticals and UCB.

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COVID-19 and rheumatology

COVID-19 and rheumatology

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