Over half of the world’s population—nearly four billion people—are at risk of contracting dengue annually. The incidence of dengue has grown dramatically around the world in recent decades, causing an estimated 390 million infections and 500,000 hospitalizations annually. The rise in cases can be attributed to factors such as urbanization, globalization, and climate change. Severe dengue accounts for about 5% of dengue cases and is a leading cause of serious illness and death among children and adults in Latin America and Asia. Currently, there isn’t an effective preventative option for individuals regardless of prior exposure to the disease.

Now, Takeda announces that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the approval of their dengue vaccine candidate, TAK-003, for the prevention of dengue disease caused by any serotype in individuals four years of age and older in Europe and in dengue-endemic countries participating in the EU-M4all procedure.

The final step in the path to approval in Europe is Marketing Authorization from the EMA, which is expected in the coming months. Regulatory reviews will also progress in dengue-endemic countries in Latin America and Asia.

“We are one step closer towards the approval of a dengue vaccine that could benefit many of the millions of individuals around the world exposed to dengue. This is a major moment for the global health community, European countries, and the dengue-endemic countries that participated in the EU-M4all procedure,” said Gary Dubin, MD, president of the global vaccine business unit at Takeda. “We have been working for many years to help improve the way dengue can be prevented. Our efforts to provide a new option for dengue prevention support Takeda’s overall goal to provide long-term societal value to the people we serve.”

Takeda’s tetravalent dengue vaccine candidate (TAK-003) is based on a live-attenuated dengue serotype 2 virus, which provides the genetic “backbone” for all four vaccine viruses.

Clinical Phase II data in children and adolescents showed that TAK-003 induced immune responses against all four dengue serotypes, in both seropositive and seronegative participants, which persisted through 48 months after vaccination, and the vaccine was found to be generally safe and well tolerated.

The Phase III Tetravalent Immunization against Dengue Efficacy Study (TIDES) trial met its primary endpoint of overall vaccine efficacy against virologically-confirmed dengue (VCD) at 12-months follow-up. It also met all secondary endpoints at 18-months follow-up for which there were a sufficient number of dengue cases, including vaccine efficacy against hospitalized dengue and in baseline seropositive and baseline seronegative individuals. Efficacy varied by serotype. The results demonstrated TAK-003 was generally well tolerated, and there have been no important safety risks observed to date.

TAK-003 was evaluated through the EMA’s first-ever parallel assessment of a medicinal product for use in the EU and non-EU countries through the EU-M4all procedure. This gives participating regulatory agencies, many of which are from dengue-endemic countries, a scientific foundation for making their own regulatory decisions.

The Committee’s positive opinion was supported by results across five Phase I, II, and III trials with more than 28,000 children and adults. This includes four and a half years of follow-up data from the global, pivotal Phase III Tetravalent Immunization against Dengue Efficacy Study (TIDES) trial, consistent with the World Health Organization’s (WHO) recommendation to obtain three to five years of follow-up data after the completion of a primary dengue vaccination in order to most accurately assess safety and efficacy. TIDES exploratory analyses showed that throughout the four and a half years of study follow-up, TAK-003 prevented 84% of hospitalized dengue cases and 61% of symptomatic dengue cases in the overall population, including both seropositive and seronegative individuals. TAK-003 has been generally well tolerated, with no evidence of disease enhancement in vaccine recipients, and no important safety risks have been identified in the TIDES trial, to date.

“The global health community has been eager for a dengue vaccine that is accessible without the barrier of pre-vaccination testing,” said Ooi Eng Eong, MD, PhD, professor of emerging infectious diseases at Duke-NUS Medical School in Singapore. “The robust clinical data provided by Takeda shows that its dengue vaccine has the potential to help prevent dengue cases and hospitalizations. Today, we are closer to helping improve dengue prevention and reducing the burden of disease on countries, communities, and health systems.”

Takeda’s dengue vaccine, known as QDENGA (TAK-003), was approved in August of this year by the Indonesia National Agency for Drug and Food Control, BADAN POM, for the prevention of dengue disease by any serotype in individuals six years to 45 years of age.

TAK-003 has not yet been approved anywhere else in the world and Takeda will continue to initiate and progress regulatory filings in other dengue-endemic and non-endemic countries. Regulatory approval and use of the vaccine are dependent on evaluation by relevant local authorities and for the indication they deem appropriate.

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