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OSAKA,
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TIDES
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About TAK-003<\/b><\/p>\n
Takeda’s
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About Dengue<\/b><\/p>\n
Dengue
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Dengue
Takeda’s Commitment to Vaccines<\/b><\/p>\n
Vaccines
Important Notice<\/b><\/p>\n
For the purposes of this notice, “press
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The companies in which Takeda directly
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Forward-Looking Statements<\/b><\/p>\n
This press release and any materials
Medical information<\/b><\/p>\n
This press release contains information
References<\/b><\/p>\n
i<\/sup> Dr.
1<\/sup> Huang CY-H,
2<\/sup> Tricou, V,
3<\/sup> Biswal S,
4 <\/sup>Biswal S, et
5<\/sup>
6<\/sup> World
7<\/sup> World
8<\/sup> Guzman MG,
9<\/sup> Knowlton K,
10<\/sup> Chan E, et
11<\/sup> Centers for
12<\/sup> UNICEF. Vaccination and Immunization Statistics<\/a>. 2019.
\nJAPAN, AND CAMBRIDGE, MASSACHUSETTS\u00a0–\u00a0Media
\nOutReach<\/a>\u00a0–\u00a025 May 2021 –\u00a0Takeda Pharmaceutical Company Limited<\/a> (TSE:4502\/NYSE:TAK<\/a>) (“Takeda”) today announced that its dengue vaccine candidate (TAK-003)
\ndemonstrated continued protection against dengue illness and hospitalization,
\nregardless of an individual’s previous dengue exposure, with no important
\nsafety risks identified through three years after vaccination in the ongoing
\npivotal Phase 3 Tetravalent Immunization against Dengue Efficacy Study<\/a> (TIDES) trial. TIDES enrolled more than 20,000 healthy
\nchildren and adolescents ages four to 16 years in dengue-endemic countries in
\nLatin America and Asia.<\/p>\n
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\nepidemics occur suddenly, and hospitals can become overwhelmed with severe
\ndisease cases and people seeking testing,” said LakKumar Fernandoi<\/sup>,
\nM.D., Center for Clinical Management of Dengue and Dengue Haemorrhagic Fever,
\nNegombo General Hospital, Sri Lanka and a primary investigator of the TIDES
\ntrial. “Results from the long-term analysis of Takeda’s dengue vaccine
\ncandidate suggest that it could help with outbreak prevention, reduce rates of
\nhospitalization and protect people from dengue regardless of their previous
\nexposure. Importantly, no important safety risks were identified.”<\/p>\n
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\nand efficacy results from the 36-month follow-up exploratory analysis of TIDES
\nwere presented on May 22, 2021, at the 17th Conference of the International
\nSociety of Travel Medicine (CISTM). Through three years (36 months after the
\nsecond dose), TAK-003 demonstrated overall vaccine efficacy (VE) of 62.0% (95%
\nCI: 56.6% to 66.7%) against virologically-confirmed dengue (VCD), with 65.0% VE
\n(95% CI: 58.9% to 70.1%) in seropositive individuals and 54.3% VE (95% CI:
\n41.9% to 64.1%) in seronegative individuals. TAK-003 also demonstrated 83.6% VE
\n(95% CI: 76.8% to 88.4%) against hospitalized dengue, with 86.0% VE (95% CI:
\n78.4% to 91.0%) in seropositive individuals and 77.1% VE (95% CI: 58.6% to
\n87.3%) in seronegative individuals. Observations of varied VE by serotype
\nremained consistent with previously reported results. No evidence of disease
\nenhancement was observed. TAK-003 was generally well tolerated, and there were
\nno important safety risks observed. The results reinforce the potential of
\nTAK-003 to help protect those who are living in or traveling to dengue-endemic
\ncountries.<\/p>\n
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\ndengue vaccine candidate continued to provide protection against dengue
\nthroughout three years, and was especially robust in preventing
\nhospitalization,” said Derek Wallace, VP, Dengue Global Program Leader at
\nTakeda. “These results reinforce my confidence that TAK-003 can help
\naddress the significant global burden of dengue.”<\/p>\n
\n
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\npreviously reported, the TIDES trial met its primary endpoint<\/a> of overall VE against VCD at 12-months follow-up (VE: 80.2%; 95% CI:
\n73.3% to 85.3%; p<0.001) and all secondary endpoints<\/a> for which there were a sufficient number of dengue cases (measured at
\n18-months follow-up). The TIDES trial has been amended to include the
\nevaluation of a booster dose to address the waning of overall VE observed over
\ntime (from 12 through 36 months after the second dose), largely driven by
\noutpatient dengue. Takeda intends to publish results of the 36-month
\nexploratory analysis in a peer-reviewed journal this year.<\/p>\n
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\nsafety and efficacy data through 36-months follow-up was included in regulatory
\nsubmissions to the European Union and dengue-endemic countries and will be part
\nof additional filings planned for 2021, including in the United States. Takeda
\nwill seek an indication for TAK-003 for the prevention of dengue disease in
\nindividuals four to 60 years of age, regardless of previous virus exposure,
\nbased on data in both adults and children. There remains a need for dengue
\nvaccines that can be used in both dengue-na\u00efve and dengue-exposed adults and
\nchildren.<\/p>\n
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\ntetravalent dengue vaccine candidate (TAK-003) is based on a live-attenuated
\ndengue serotype 2 virus, which provides the genetic “backbone” for all four
\nvaccine viruses.1<\/sup> Clinical Phase 2<\/a> data in children and
\nadolescents showed that TAK-003 induced immune responses<\/a> against all four dengue serotypes, in both seropositive
\nand seronegative participants, which persisted through 48 months after vaccination,
\nand the vaccine was found to be generally safe and well tolerated.2<\/sup>
\nThe pivotal Phase 3 Tetravalent Immunization against Dengue Efficacy Study
\n(TIDES) trial met its primary endpoint of overall vaccine efficacy<\/a> (VE) against virologically-confirmed dengue (VCD) at
\n12-months follow-up and all secondary endpoints at 18-months follow-up<\/a> for which there were a sufficient number of dengue
\ncases, including VE against hospitalized dengue and VE in baseline seropositive
\nand baseline seronegative individuals.3,4<\/sup> Efficacy varied by
\nserotype. The results demonstrated TAK-003 was generally well tolerated, and
\nthere have been no important safety risks observed to date.<\/p>\n
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\ndouble-blind, randomized, placebo-controlled Phase 3 Tetravalent Immunization
\nagainst Dengue Efficacy Study (TIDES) trial is evaluating the safety and
\nefficacy of two doses of TAK-003 in the prevention of laboratory-confirmed
\nsymptomatic dengue fever of any severity and due to any of the four dengue
\nvirus serotypes in children and adolescents.4<\/sup> The TIDES trial is
\nTakeda’s largest interventional clinical trial to date and enrolled over 20,000
\nhealthy children and adolescents ages four to 16 years living in dengue-endemic
\nareas. Study participants were randomly assigned to receive either TAK-003 0.5
\nmL or placebo by subcutaneous injection on Day 1 and Day 90.4<\/sup> The
\nstudy is comprised of five parts. Part 1 and the primary endpoint analysis
\nevaluated vaccine efficacy (VE) and safety through 12 months after the second
\ndose.4<\/sup> Part 2 continued for an additional six months to complete the
\nassessment of the secondary endpoints of VE by serotype, baseline serostatus
\nand disease severity, including VE against hospitalized dengue.4<\/sup>
\nPart 3 is evaluating VE and long-term safety by following participants for an
\nadditional two and a half to three years.5<\/sup> Part 4 will evaluate
\nefficacy and safety for 13 months following booster vaccination and Part 5 will
\nevaluate long-term efficacy and safety for one year after completion of Part 4.5<\/sup><\/p>\n
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\ntrial is taking place at sites in dengue-endemic areas in Latin America
\n(Brazil, Colombia, Panama, the Dominican Republic and Nicaragua) and Asia
\n(Philippines, Thailand and Sri Lanka) where there are unmet needs in dengue
\nprevention and where severe dengue is a leading cause of serious illness and
\ndeath among children.4<\/sup> Baseline blood samples were collected from
\nall individuals participating in the trial to allow for evaluation of safety
\nand efficacy based on serostatus. Takeda and an independent Data Monitoring
\nCommittee of experts are actively monitoring safety on an ongoing basis.<\/p>\n
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\nis the fastest spreading mosquito-borne viral disease and was one of the WHO’s
\ntop 10 threats to global health in 2019.6,7<\/sup> Dengue is mainly spread
\nby Aedes aegypti mosquitoes and, to a lesser extent, Aedes albopictus mosquitoes.
\nIt is caused by any of four dengue virus serotypes, each of which can cause
\ndengue fever or severe dengue. The prevalence of individual serotypes varies
\nacross different geographies, countries, regions, seasons and over time.8<\/sup>
\nRecovery from infection by one serotype provides lifelong immunity against only
\nthat serotype, and later exposure to any of the remaining serotypes is
\nassociated with an increased risk of severe disease.<\/p>\n
\n
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\nis pandemic prone, and outbreaks are observed in tropical and sub-tropical
\nareas and have recently caused outbreaks in parts of the continental United
\nStates and Europe.9,10<\/sup> Approximately half of the world now lives
\nunder the threat of dengue, which is estimated to cause 390 million infections
\nand around 20,000 deaths globally each year.10,11<\/sup> The dengue virus
\ncan infect people of all ages and is a leading cause of serious illness among
\nchildren in some countries in Latin America and Asia.10<\/sup><\/p>\n
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\nprevent 2 to 3 million deaths each year and have transformed global public
\nhealth.12<\/sup> For the past 70 years, Takeda has supplied vaccines to
\nprotect the health of people in Japan. Today, Takeda’s global vaccine business
\nis applying innovation to tackle some of the world’s most challenging infectious
\ndiseases, such as dengue, COVID-19, Zika and norovirus. Takeda’s team brings an
\noutstanding track record and a wealth of knowledge in vaccine development,
\nmanufacturing and global access to advance a pipeline of vaccines to address
\nsome of the world’s most pressing public health needs. For more information,
\nvisit https:\/\/www.takedavaccines.com\/<\/a>.<\/p>\n
\n
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\n
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\nrelease” means this document, any oral presentation, any question and answer
\nsession and any written or oral material discussed or distributed by Takeda
\nPharmaceutical Company Limited (“Takeda”) regarding this release. This press
\nrelease (including any oral briefing and any question-and-answer in connection
\nwith it) is not intended to, and does not constitute, represent or form part of
\nany offer, invitation or solicitation of any offer to purchase, otherwise
\nacquire, subscribe for, exchange, sell or otherwise dispose of, any securities
\nor the solicitation of any vote or approval in any jurisdiction. No shares or
\nother securities are being offered to the public by means of this press
\nrelease. No offering of securities shall be made in the United States except
\npursuant to registration under the U.S. Securities Act of 1933, as amended, or
\nan exemption therefrom. This press release is being given (together with any
\nfurther information which may be provided to the recipient) on the condition
\nthat it is for use by the recipient for information purposes only (and not for
\nthe evaluation of any investment, acquisition, disposal or any other
\ntransaction). Any failure to comply with these restrictions may constitute a
\nviolation of applicable securities laws.<\/p>\n
\n
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\n
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\nand indirectly owns investments are separate entities. In this press release,
\n“Takeda” is sometimes used for convenience where references are made to Takeda
\nand its subsidiaries in general. Likewise, the words “we”, “us” and “our” are
\nalso used to refer to subsidiaries in general or to those who work for them.
\nThese expressions are also used where no useful purpose is served by
\nidentifying the particular company or companies.<\/p>\n
\n
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\n
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\n
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\ndistributed in connection with this press release may contain forward-looking
\nstatements, beliefs or opinions regarding Takeda’s future business, future
\nposition and results of operations, including estimates, forecasts, targets and
\nplans for Takeda. Without limitation, forward-looking statements often include
\nwords such as “targets”, “plans”, “believes”, “hopes”, “continues”, “expects”,
\n“aims”, “intends”, “ensures”, “will”, “may”, “should”, “would”, “could”
\n“anticipates”, “estimates”, “projects” or similar expressions or the negative
\nthereof. These forward-looking statements are based on assumptions about many
\nimportant factors, including the following, which could cause actual results to
\ndiffer materially from those expressed or implied by the forward-looking
\nstatements: the economic circumstances surrounding Takeda’s global business,
\nincluding general economic conditions in Japan and the United States;
\ncompetitive pressures and developments; changes to applicable laws and
\nregulations, including global health care reforms; challenges inherent in new
\nproduct development, including uncertainty of clinical success and decisions of
\nregulatory authorities and the timing thereof; uncertainty of commercial success
\nfor new and existing products; manufacturing difficulties or delays;
\nfluctuations in interest and currency exchange rates; claims or concerns
\nregarding the safety or efficacy of marketed products or product candidates;
\nthe impact of health crises, like the novel coronavirus pandemic, on Takeda and
\nits customers and suppliers, including foreign governments in countries in
\nwhich Takeda operates, or on other facets of its business; the timing and
\nimpact of post-merger integration efforts with acquired companies; the ability
\nto divest assets that are not core to Takeda’s operations and the timing of any
\nsuch divestment(s); and other factors identified in Takeda’s most recent Annual
\nReport on Form 20-F and Takeda’s other reports filed with the U.S. Securities and
\nExchange Commission, available on Takeda’s website at: https:\/\/www.takeda.com\/investors\/reports\/sec-filings\/<\/a> or at www.sec.gov<\/a>. Takeda does not undertake to update any of the forward-looking
\nstatements contained in this press release or any other forward-looking
\nstatements it may make, except as required by law or stock exchange rule. Past
\nperformance is not an indicator of future results and the results or statements
\nof Takeda in this press release may not be indicative of, and are not an
\nestimate, forecast, guarantee or projection of Takeda’s future results.<\/p>\n
\n
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\nabout products that may not be available in all countries, or may be available
\nunder different trademarks, for different indications, in different dosages, or
\nin different strengths. Nothing contained herein should be considered a
\nsolicitation, promotion or advertisement for any prescription drugs including
\nthe ones under development.<\/p>\n
\n
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\n
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\nLakKumar Fernando did not receive compensation for his statement.<\/p>\n
\n
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\net al. Genetic and phenotypic characterization of manufacturing seeds for
\ntetravalent dengue vaccine (DENVax). PLoS Negl Trop Dis. 2013;7:e2243.<\/p>\n
\n
<\/p>\n
\nS\u00e1ez-Llorens X, et al. Safety and immunogenicity of a tetravalent dengue vaccine in children
\naged 2-17 years: a randomised, placebo-controlled, phase 2 trial<\/a>. Lancet. 2020. doi:10.1016\/S0140-6736(20)30556-0.<\/p>\n
\n
<\/p>\n
\net al. Efficacy of a tetravalent dengue vaccine in healthy children and
\nadolescents. N Engl J Med. 2019;2019;381:2009-2019.<\/p>\n
\n
<\/p>\n
\nal. Efficacy of a tetravalent dengue vaccine in healthy children aged 4-16
\nyears: a randomized, placebo controlled, phase 3 trial. Lancet. 2020.
\n2020;395:1423-1433.<\/p>\n
\n
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\nClinicalTrials.Gov. Efficacy, Safety and Immunogenicity of Takeda’s Tetravalent Dengue
\nVaccine (TDV) in Healthy Children (TIDES)<\/a>. Retrieved
\nMarch 2021.<\/p>\n
\n
<\/p>\n
\nHealth Organization. Factsheet. Dengue and Severe Dengue<\/a>. April
\n2019. Retrieved February 2021.<\/p>\n
\n
<\/p>\n
\nHealth Organization. Ten threats to global health in 2019<\/a>. 2019.
\nRetrieved February 2021.<\/p>\n
\n
<\/p>\n
\net al. Dengue: a continuing global threat<\/a>. Nature
\nReviews Microbiology. 2010;8:S7-S16.<\/p>\n
\n
<\/p>\n
\net al. Mosquito-Borne Dengue Fever Threat Spreading in the Americas<\/a>. The Natural Resources Defense Council (NRDC). 2009. Retrieved February
\n2021.<\/p>\n
\n
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\nal. Using web search query data to monitor dengue epidemics: a new model for
\nneglected tropical disease surveillance. PLoS Negl Trop Dis. 2011;5:e1206.<\/p>\n
\n
<\/p>\n
\nDisease Control and Prevention. About
\nDengue: What You Need to Know<\/a>. May 2019.
\nRetrieved February 2021.<\/p>\n
\n
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\nRetrieved February 2021.<\/p>\n