FDA authorizes AstraZeneca antibody cocktail for pre-exposure prevention of COVID-19
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The FDA has for the first time approved an emergency use authorization for a long-acting monoclonal antibody cocktail designed to prevent symptomatic COVID-19 among adults and children aged 12 years and older.
According to data submitted to the FDA, AstraZeneca’s Evusheld (tixagevimab plus cilgavimab), also known as AZD7442, can reduce the risk for developing symptomatic COVID-19 by 77%, compared with placebo, among unvaccinated adults without prior SARS-CoV-2 infection at increased risk for inadequate immunization response.
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Alfred H.J. Kim, MD, PhD, assistant professor of medicine in the division of rheumatology at the Washington University School of Medicine, in St. Louis, Missouri, noted that Wednesday’s approval represents a significant step forward in the protection of immunocompromised patients.
“This is really great news for the immunosuppressed in general, but particularly those on medications that put them at high risk for very poor or absent antibody responses,” Kim told Healio Rheumatology. “These patients now have a way to have protective antibodies. The timing of this is especially good, since cases are spiking due to colder weather — and the holidays are coming up. If it can be administered prior to holiday engagements, this will provide an extra layer of protection for them.”
According to Kim, the Evusheld EUA will have a particularly profound impact on patients receiving TNF inhibitors, as these individuals appear unable to neutralize the delta variant of the SARS-CoV-2 virus, even when vaccinated. Although COVID-19 booster shots can alleviate this concern, they may not be an option for patients who experienced adverse reactions to the vaccine.
“This pre-exposure prophylaxis (PrEP) can neutralize delta in these patients,” Kim said. “Given the number of people on TNF inhibitors, for rheumatoid arthritis, psoriatic arthritis, ulcerative colitis and more, this could help provide an extra protection that they don’t quite have right now. I should add that patients on TNF inhibitors who receive the booster dose can generate a response to delta. However, if they had a reaction to the vaccine, PrEP solid alternative.”
Kim added that he and his colleagues will now focus on administering the newly available cocktail to their B-cell depleted patients, as well as those receiving mycophenolate, considering both populations are at risk for having an inadequate response to COVID-19 vaccines.
The FDA’s EUA authorizes the drug only for adults and children aged 12 years and older, weighing at least 40 kg, who are not currently infected with SARS-CoV-2, and who have not recently been exposed to COVID-19. The emergency authorization also requires that individuals either have moderate to severely compromised immune systems, due to a medical condition or immunosuppressive medications or treatments, leading to a potentially inadequate immune response to COVID-19 vaccination, or a history of severe adverse reactions to a COVID-19 vaccine and/or components of the vaccines.
Evusheld is not authorized for individuals to treat COVID-19 or for post-exposure prevention of COVID-19. The FDA also stressed that Evusheld is not a substitute for vaccination among those for whom vaccination is recommended.
The FDA based their approval on data from the phase 3 PROVENT trial, which examined the efficacy and safety of Evusheld in 5,197 participants across 87 sites in the United States, United Kingdom, Spain, France and Belgium. Participants were unvaccinated adults without prior SARS-CoV-2 infection who had an increased risk for inadequate response to active immunization, or an increased risk for COVID-19, including those whose location or circumstances increased their chances of infection.
According to AstraZeneca, more than 75% of those enrolled demonstrated baseline comorbidities and other characteristics associated with an increased risk for severe COVID-19, including immunosuppressive disease or receiving immunosuppressive medications, diabetes, severe obesity or cardiac disease, chronic obstructive pulmonary disease, and chronic kidney and chronic liver disease.
Participants were randomly assigned 2:1 to receive either a single, intramuscular 300 mg dose of Evusheld or a saline placebo, administered in two sequential injections.
According to the PROVENT researchers, Evusheld reduced the risk for symptomatic COVID-19 by 77% (95% CI, 46% to 90%), compared with placebo. None of the participants who received the monoclonal cocktail developed severe COVID-19, and none died. Meanwhile, the placebo arm saw three cases of severe COVID-19, including two deaths. The trial reported a total of 25 cases of symptomatic COVID-19 across both groups at the primary analysis.
Regarding safety, Evusheld was well tolerated, with the preliminary analyses demonstrating balanced adverse events between the placebo and treatment groups.
AstraZeneca’s request for an EUA also included data from the phase 3 STORM CHASER trial, which analyzed efficacy and safety among more than 1,100 unvaccinated adults who were exposed to SARS-CoV-2 within the past 8 days. The study suggested that the cocktail shrunk the risk for symptomatic COVID-19 by 33% (95% CI, –26% to 65%), compared with placebo. However, this result was not significant, and the trial did not meet its primary endpoint.
Evusheld is a combination of two long-acting antibodies — tixagevimab (AZD8895) and cilgavimab (AZD1061) — derived from B-cells donated by convalescent patients after SARS-CoV-2 infection. It was discovered at Vanderbilt University Medical Center, in Nashville, with support from the U.S. Department of Health and Human Services and the Department of Defense, and licensed to AstraZeneca in June 2020.
Perspective
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The announcement of the EUA for AstraZeneca’s Evusheld (tixagevimab administered together with cilgavimab) for the pre-exposure prophylaxis (PrEP) of COVID-19 in certain adults with moderate to severely compromised immune systems due to a medical condition, immunosuppressive medications or treatments and may not mount an adequate immune response to COVID-19 vaccination is great news for a large group of patients with immune mediated inflammatory diseases (IMIDs), as well as other conditions such as cancer, transplantation and immunodeficiencies.
A one-time intramuscular injection may afford protection for up to 6 months, virtually on par with effective vaccination. The patients for whom this is optimally designed are precisely those who are least likely to mount their own immune response to the vaccines that have benefited so many among the general population. I am particularly excited for many patients who have, up until now, done everything they can to protect themselves — including vaccinations, mask wearing and social distancing —but have been far more vulnerable to severe COVID than the general vaccinated population. It is a game-changer for them.
There is much to sort out in this EUA right now, particularly where we will be drawing the line among the nearly 3% of the population who fall under this general category and merit COVID-19 PrEP right now.
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