AstraZeneca’s Evusheld, a combination of long-acting antibodies tixagevimab and cilgavimab (formerly AZD7442), has EU approval for adults and adolescents aged 12 and older who weigh at least 40 kg and do not require supplemental oxygen. The treatment aims to identify individuals at elevated risk of progressing to severe COVID-19 and to provide a preventive and therapeutic option within the European health system.
The European Commission granted this approval on the basis of results from the Phase III TACKLE treatment trial. The intramuscular antibody pair showed clinically and statistically significant protection against progression to severe COVID-19 or death from any cause when compared with placebo. Early intervention—especially for non-hospitalized adults with mild to moderate symptoms for seven days or less—yielded more favorable outcomes. About 90% of trial participants carried at least one risk factor for severe disease due to age or comorbidities, and the regimen was generally well tolerated.
In remarks highlighting the ongoing commitment to public health, a representative from AstraZeneca emphasized the company’s continued role in the fight against COVID-19. The approval positions Evusheld as a potent option to protect infected patients at high risk of complications, and AstraZeneca reaffirmed its collaboration with governments and health institutions to protect populations and reduce hospitalizations and mortality related to the virus.
Experts note that a large segment of the population remains at elevated risk, including immunocompromised individuals, older adults, and those with chronic health conditions. The intramuscular antibody combination offers a new treatment avenue for these vulnerable groups, potentially reducing hospitalizations and deaths if infection occurs.
Leaders in vaccines and immunotherapies underscore that COVID-19 continues to present health concerns globally, particularly among those not adequately protected by vaccination. The long-acting antibody therapy now has authorization in Europe for both prevention and treatment, broadening protection against the disease.
The European recommended dose consists of 300 mg of tixagevimab and 300 mg of cilgavimab, delivered as two separate sequential intramuscular injections.
In Europe, the antibody combination has shown preserved in vitro neutralization against the Omicron BA.5 variant, which has become the dominant strain in the region. Real-world data indicate notably lower rates of symptomatic COVID-19 and of hospitalization or death among immunocompromised patients treated with tixagevimab and cilgavimab compared with control groups, including experience gathered during Omicron waves BA.5, BA.4, BA.2, BA.1, and BA.1.1.
The EU previously authorized Evusheld for pre-exposure prophylaxis in immunocompromised patients, and it is now available across most European countries, including Spain. [Citation: EU regulatory authority release].
FISHING ROD
The TACKLE study was a Phase III multicenter, randomized, double-blind, placebo-controlled trial evaluating a single 600 mg intramuscular dose of the antibody combination (300 mg cilgavimab plus 300 mg tixagevimab) versus placebo for treating mild to moderate COVID-19. Conducted at 95 centers across the United States, Latin America, Europe, and Japan, the trial enrolled 903 adults aged 18 and older with mild to moderate disease who had been symptomatic for seven days or less and who were not vaccinated at screening. [Citation: Lancet Respiratory Medicine trial report].
Results published in Lancet Respiratory Medicine showed that the antibody combination significantly reduced the relative risk of progression to severe COVID-19 or any-cause death by 50 percent by day 29 in non-hospitalized patients with mild to moderate disease. In prespecified analyses, treatment within three days of symptom onset reduced the risk by 88 percent, while treatment within five days reduced risk by 67 percent compared with placebo. The regimen was generally well tolerated, with adverse events more common in the placebo group. COVID-19 pneumonia occurred in 11 percent of placebo participants and 6 percent of those receiving the antibody combination. Severe adverse events occurred in 12 percent of the placebo group and 7 percent of the treated group, with six deaths in the placebo arm and three in the treatment arm. [Citation: Lancet Respir Med publication].
Previously known as AZD7442, this therapy combines two long-acting antibodies, tixagevimab and cilgavimab, derived from B cells of convalescent patients after SARS-CoV-2 infection. Discovered at Vanderbilt University Medical Center and licensed to AstraZeneca in June 2020, the antibodies target distinct sites on the spike protein of SARS-CoV-2. They were optimized to prolong half-life and reduce Fc effector function, aiming to minimize potential antibody-enhanced disease. The extended half-life provides protection for roughly six months, and the reduced Fc function seeks to limit adverse immune reactions.
The antibody combination has regulatory authorization for prevention in the United States under emergency use, and for treatment in the EU, Japan, and multiple other countries. It is also approved in Japan for preventing severe SARS-CoV-2 infection in individuals with risk factors. Ongoing submissions worldwide are pursuing both preventive and therapeutic indications. [Citation: regulatory status summaries].