AstraZeneca’s AZD7442 (tixagevimab and cilgavimab), a long-acting antibody combination, has been approved in Japan for both prevention (pre-exposure prophylaxis) and treatment of symptomatic disease caused by SARS-CoV-2 infection. The decision marks the first global marketing approval for AZD7442 as a treatment for COVID-19.
In prevention, Japan’s Ministry of Health, Labour and Welfare (MHLW) granted AZD7442 Special Approval for Emergency for adults and adolescents (12 years of age and older weighing at least 40kg). AZD7442 is approved for use in those whom SARS-CoV-2 vaccination is not recommended and who may have an inadequate response to a COVID-19 vaccine due to immunodeficiencies. Recipients of AZD7442 for prevention should not be currently infected with or have had recent known exposure to a person infected with SARS- CoV-2.
In treatment, AZD7442 is approved for adults and adolescents (12 years of age and older weighing at least 40kg) with risk factors for severe SARS-CoV-2 infection who do not require supplemental oxygen.
Kazuhiro Tateda, M.D. Ph.D., Professor, Department of Microbiology and Infectious Disease, Toho University, Tokyo, Japan, said: “COVID-19 continues to have a significant impact on our daily lives in Japan. Many people, including older adults, patients with comorbidities, and immunocompromised patients, remain at risk for poor outcomes from severe COVID-19. AZD7442 will be a much-needed new option, offering long-term protection for those who do not achieve an adequate immune response after vaccination and helping prevent severe disease and death in those who do become infected.”
Itaru Matsumura, M.D., Ph.D. Professor & Chairman, Department of Hematology & Rheumatology, Kindai University Faculty of Medicine, Otsuka, Japan, said: “Despite the progress of vaccinations and stringent safety precautions, there are very large number of new infections in Japan. The approval of AZD7442 is expected to provide a non-vaccine prophylactic option for those who cannot expect a full immune response from COVID-19 vaccination, such as patients with blood cancers.”
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “The approvals of AZD7442 in Japan represent an important milestone in our ongoing efforts to
help combat COVID-19 on all fronts. AZD7442 is now the only long-acting antibody combination authorised for both COVID-19 prevention and treatment, allowing us to help protect even more vulnerable patients such as the immunocompromised from this devastating disease.”
The Japanese government has agreed to purchase 300,000 units of AZD7442 (150mg each of tixagevimab and cilgavimab) and AstraZeneca is working with the government and partners to make first doses available as soon as possible.
The approvals were based on efficacy and safety data from the AZD7442 clinical development programme, including the PROVENT Phase III pre-exposure prophylaxis trial, the TACKLE Phase III outpatient treatment trial, and Phase I trials, including in Japan. In PROVENT, a 300mg intramuscular (IM) dose of AZD7442 significantly reduced the risk of developing symptomatic COVID-19 by 77% (95% confidence interval (CI): 46, 90; p<0.001) COVID-19 compared to placebo at the primary analysis.1 An 83% (95% CI: 66, 91) relative risk reduction was shown at a six-month median follow-up analysis, with protection from the virus lasting six months.1
In TACKLE, a 600mg IM dose of AZD7442 significantly reduced the relative risk of progressing to severe COVID-19 or death (from any cause) by 50% (95% confidence interval [CI] 15, 71; p=0.010) through day 29 compared to placebo in non-hospitalised patients with mild-to-moderate COVID-19 who were symptomatic for seven days or less, the trial’s primary endpoint.2 In pre-specified analyses of participants who received treatment within three days of symptom onset, AZD7442 reduced the risk of developing severe COVID-19 or death (from any cause) by 88% compared to placebo (95% CI 9, 98), and the risk reduction was 67% (95% CI 31, 84) when participants received AZD7442 within five days of symptom onset.2
AZD7442 was generally well-tolerated in the trials.1,2
The recommended dose for prevention of symptomatic disease caused by SARS-CoV-2 infection in Japan is 150mg of tixagevimab and 150mg of cilgavimab, administered as separate sequential IM injections. Depending on the prevalence of SARS-CoV-2 variants, 300mg of tixagevimab and 300mg of cilgavimab may be administered for prevention. The recommended dose for treatment of COVID-19 is 300mg of tixagevimab and 300mg of cilgavimab, administered as separate sequential IM injections.
AZD7442 has been shown to retain in vitro neutralisation activity against the main Omicron variants currently circulating globally, including BA.5 and BA.2.3,4
AZD7442 is also authorised for use for pre-exposure prophylaxis (prevention) of COVID-19 in the US (emergency use), EU and many other countries. Regulatory submissions are progressing for both prevention and treatment indications around the world.