Dengue vaccine! Takeda tetravalent vaccine tak-003 is 73% effective at 18 months in 4-16-year-old children, regardless of previous infection or not!

November 25, 2019 / BIOON / -- Takeda, a Japanese pharmaceutical giant, recently announced the latest results of the key phase III tides Research (nct02747927) of dengue candidate vaccine tak-003 at the 68th annual meeting of the American Society of Tropical Medicine and health (ASTMH) Tak-003 is a attenuated tetravalent dengue vaccine It was developed based on the attenuated dengue hemagglutinin type 2 virus (DENV-2), which provides a genetic skeleton for all four vaccine viruses Data from phase I and phase II studies showed that tak-003 induced neutralizing antibodies against four serotypes of dengue virus in all age groups, seropositive individuals and seronegative individuals, and the vaccine was safe and well tolerated The phase III tides study, Takeda's largest intervention clinical study to date, is a double-blind, randomized, placebo-controlled study of more than 20000 healthy children and adolescents aged 4-16 years in countries in Latin America and Asia where dengue fever is prevalent The purpose of this study is to assess the protection of dengue by two doses of immune (3-month interval) tak-003 or placebo The study will also assess the safety and immunogenicity of the vaccine The primary endpoint analysis evaluated the vaccine efficacy (VE) and safety 15 months after the first injection (12 months after the second injection) The second part of the study continued for an additional six months to complete the secondary end point of VE by serotype, baseline serum status, and disease severity The final part of the study evaluated ve and long-term safety by conducting an additional three-year follow-up of participants The data presented at the meeting included: total ve update data 18 months after the second injection and formal evaluation results of secondary efficacy endpoint by serotype, baseline serum status and disease severity The results showed that the tides trial reached all secondary endpoints in terms of a sufficient number of cases The results of total ve and safety in the second part of the study were basically consistent with the data in the primary endpoint analysis report: 73.3% (95% CI: 66.5% - 78.8%) of the total VE in the second injection at 18 months, and 80.2% (95% CI: 73.3% - 85.3%, P < 0.001) of the VE in the primary endpoint analysis (12 months after the second injection) The total ve data of the primary endpoint analysis was published in the New England Journal of Medicine (NEJM) at the beginning of this month The data showed that in children and adolescents aged 4-16 years, the total ve of tak-003 to virologically confirmed dengue fever (VCD) was 80.2% (95% CI: 73.3% to 85.3%, P < 0.001) after the second immunization and 12 months follow-up The evaluation of secondary end points showed that the VE of tak-003 for hospitalized dengue fever was 90.4% (95% CI: 82.6 to 94.7%, P < 0.001), and the VE for bleeding dengue fever was 85.9% (95% CI: 31.9 to 97.1%); due to the insufficient number of cases, the efficacy of tak-003 for severe VCD could not be determined (VE: 2.3% [95% CI: - 977.5% to 91.1%]) The overall efficacy was similar in baseline serum positive patients (VE: 76.1% [95% CI: 68.5% to 81.9%]) and serum negative patients (VE: 66.2% [95% CI: 49.1% to 77.5%]) The curative effect of different serotypes was different: the VE of type 1 was 69.8% (95% CI: 54.8% to 79.9%), that of type 2 was 95.1% (95% CI: 89.9% to 97.6%), and that of type 3 was 48.9% (95% CI: 27.2% to 64.1%) The number of cases of type 4 was insufficient to fully evaluate the efficacy (VE: 51.0% [95% CI: - 69.4% to 85.8%]) Secondary efficacy endpoints will continue to be evaluated during the trial Analysis of the exploratory end point of VCD showed that tak-003 had similar VE in both serum positive and serum negative type 1 (VE: 72.0% [95% CI: 52.2% to 83.6%] vs ve: 67.8% [95% CI: 40.3% to 82.6%]) and type 2 (VE: 93.7% [95% CI: 86.1% to 97.1%] vs ve: 98.1% [95% CI: 85.8% to 99.7%]) For type 3, VE was 61.8% (95% CI: 43.0% - 74.4%) in serum positive patients and - 68.2% (95% CI: 318.9% - 32.4%) in serum negative patients There is no statistical conclusion on VE for type 3, but it shows a lack of efficacy Due to the limited number of cases, the efficacy of type 4 cannot be determined Planned follow-up will further determine the performance of the candidate vaccine in types 3 and 4 In line with the results of previous studies, tak-003 is generally well tolerated and no significant safety risks have been observed so far At present, the phase III tides test is in progress, and the safety and effectiveness of tak-003 in the study object will continue to be evaluated for four and a half years It should be noted that the candidate vaccine has not yet been approved by any regulatory body around the world Shibadas biswal, director of clinical development medicine of dengue fever in Takeda, said: "the 18 month data provided at the ASTMH meeting further deepened our understanding of the effectiveness and safety of Takeda candidate dengue fever vaccine tak-003 These results are encouraging, and we are particularly pleased to see that the overall efficacy is consistent with our 12-month analysis, as is the overall efficacy of serum negative participants Although more data is needed to fully understand the overview of tak-003, especially serum negative serotype 3, we believe that the vaccine has the potential to address key priorities for dengue epidemic control, including the protection of serum negative populations and prevention of hospitalization " Dengvaxia: the first dengue vaccine in the world At present, Sanofi has only one dengue vaccine product on the market That is, dengvaxia, a 20-year-old vaccine product developed by Sanofi, a French pharmaceutical giant The vaccine was approved by Mexico in December 2015, as the first dengue vaccine product approved in the world Since then, the vaccine has been approved by several dengue endemic countries in Latin America and Asia, and it was approved by the European Union in December 2018 In the United States, dengvaxia was approved by the FDA in May this year, becoming the first and only medical prevention tool for dengue fever in the U.S market Dengue is an acute mosquito borne disease caused by dengue virus The clinical manifestations are high fever, headache, severe muscle and joint pain, skin rash, bleeding tendency, lymphadenopathy, leucopenia, thrombocytopenia, etc dengue fever is one of the main causes of children's death in Southeast Asia Dengue is a mosquito borne disease, commonly known as "breakbone fever", which threatens nearly 3 billion people around the world and is prevalent in Asia and Latin America According to the World Health Organization (who), more than 100 million people are infected with dengue fever every year Dengue fever is often misdiagnosed due to a wide range of clinical symptoms ranging from mild non-specific to life-threatening complications At the same time, the limitations of the monitoring system are also the cause of insufficient reporting of dengue cases Worldwide, 500000 people (including children) suffer from dengue haemorrhagic fever (DHF) every year Timely access to appropriate medical care is essential to reduce the risk of serious dengue death WHO has set the target to reduce dengue fever mortality by 50% and incidence rate by 25% by 2020 At present, dengue haemorrhagic fever has not any targeted treatment drugs Dengue fever is caused by four different serotypes of dengue virus There is no immune effect among the virus strains, so it can be repeatedly infected by different serotypes of dengue virus It is estimated that about 67 million people are infected with dengue every year in Asia, which accounts for about 70% of the global dengue burden In Asian endemic countries, the direct and indirect medical expenditure caused by dengue fever is up to US $6.5 billion per year Original source: Takeda presentations 18 month data from pivotal phase 3 trial of dengue vaccine candidate at the American Society of Tropical Medicine and hygiene (ASTMH) 68th annual meeting