Japan firm Takeda’s dengue vaccine gets WHO panel backing, but no nod yet for phase 3 trials in India

New Delhi: A scientific advisory panel under the World Health Organization (WHO) has recommended a vaccine developed by Japanese pharma giant Takeda against dengue — a viral infection caused by the dengue virus (DENV), transmitted to humans through the bite of infected mosquitoes — for use in endemic countries.

“The live-attenuated quadrivalent dengue vaccine (TAK-003 or QDENGA) developed by Takeda has demonstrated efficacy against all four serotypes of the virus in baseline seropositive children (4-16 years) in endemic countries and against serotypes 1 and 2 in baseline seronegative children,” WHO said in a statement Monday. 

Dengue has emerged as a major public health challenge in recent times in several countries including India, where this year, a total of 94,198 cases and 91 deaths due to the disease have been reported so far according to health ministry data. Last year, India had registered 2,33,251 dengue cases and 303 related deaths.

Takeda is also planning to carry out a phase 3 clinical trial of the vaccine in India, but is still waiting for approval from the Drug Controller General of India (DCGI), officials in the Central Drugs Standard Control Organisation (CDSCO) told ThePrint. The DCGI heads the CDSCO. 

Takeda said in a statement Tuesday that WHO experts had reviewed data from QDENGA’s phase 1, 2 and 3 trials with more than 28,000 participants and the agency will consider the SAGE recommendation and provide final guidance on the use of QDENGA in public vaccination programmes in coming months. 

QDENGA is based on a live-attenuated dengue serotype 2 virus, which provides the genetic “backbone” for all four dengue virus serotypes (distinctive groups within a species of organisms like bacteria or viruses), and is designed to protect against any of these serotypes, the company said. The vaccine is already approved in Europe, the UK, Brazil, Argentina, Indonesia and Thailand.

“The company (Takeda) had applied for the trial early this year but was asked to submit a different trial design, which it did sometime back,” a senior CDSCO official told ThePrint. “Now we are in the process of assessing the revised application.”

Takeda is yet to revert to emailed queries by ThePrint on the status of the vaccine clinical trial in India.

ThePrint also reached DCGI Rajeev Singh Raghuvanshi via calls for comment on regulatory approval for the vaccine. This report will be updated if and when a response is received.

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Advantages of a vaccine that protects against all 4 dengue strains

Dengue was one of the WHO’s top 10 threats to global health in 2019. 

Symptoms of the disease include high fever, headache, vomiting, muscle and joint pain accompanied by skin rashes and itching. In some patients, the disease can be severe, leading to dengue hemorrhagic fever, in which case there can be bleeding, low platelet levels and blood plasma leakage or dangerously low blood pressure.

It is mainly spread by Aedes aegypti mosquitoes and, to a lesser extent, by Aedes albopictus mosquitoes. The disease can be caused by any of the four dengue virus serotypes, each of which can cause dengue fever or severe dengue.

The prevalence of individual serotypes varies across different geographies, countries, regions, seasons, and over time. Recovery from infection by one serotype provides lifelong immunity against only that serotype, and later exposure to any of the remaining serotypes is associated with an increased risk of severe disease.

While maximum dengue cases are reported during the post-monsoon season in India, sporadic cases are recorded throughout the year. 

The WHO statement said that dengue poses a significant public health burden in endemic countries and is poised to increase further both in terms of incidence and geographic expansion, due to climate change and urbanisation.

Back home, the disease incidence and spread has also reached worrying levels. In a press conference in May, health ministry officials had said that while the disease was limited to eight states in 2001, it has now reached all states and Union territories in the country, including Ladakh where first cases were reported this year.

Dr Amitabh Parti, director of internal medicine with Fortis Memorial Research Institute, Gurugram, stressed that India is currently facing the challenge of nearly four strains of dengue, and each strain seems to be becoming more and more fatal for potential patients. 

“Therefore, we need to create a vaccine that targets all four serotypes of the virus strains. Once we develop a partial virus or partial vaccine against DENV-1 and DENV-2 strains, the other strains may become more lethal,” he said. 

Dr Parti further said that a comprehensive vaccine that works against all four strains “would be highly successful in the Indian context”. 

“This is particularly important because a significant portion of the Indian population has experienced dengue fever more than once, meaning they have been exposed to one or two strains,” he added.

In the current scenario, the clinician said, to protect not only those who have been exposed to the first and second strains or the third and fourth strains but also individuals who have had no previous exposure to the dengue virus, a comprehensive vaccine would provide potential protection against future episodes of severe and fatal dengue. 

Given the large number of breeding mosquitoes and the endemic nature of the disease in various parts of the country, having such a stable vaccine that covers all four strains would be immensely beneficial to the large population, Dr Parti added.

Other dengue vaccines in pipeline

Apart from QDENGA, only one other dengue vaccine — DENGVAXIA by Sanofi — is approved for use in some countries such as the US.

This vaccine, however, is indicated only for use in individuals aged 6 through 16 years with laboratory-confirmed previous dengue infection and living in endemic areas. It is not available in India. 

At least three Indian companies — the Serum Institute of India (SII), Indian Immunologicals Ltd. and Panacea Biotec — are also working on developing vaccines that protect against all four strains of dengue. 

The vaccine developed by SII has already undergone phase 1 clinical trials in Australia which showed promising results. The company had applied to the CDSCO for permission to conduct a late stage trial in India. 

But a company spokesperson told ThePrint that the CDSCO has asked the vaccine-maker to carry out a phase 1 trial in India too, in order to establish the safety profile of the vaccine candidate in the Indian population. 

“It will start very soon and will be followed by phase 2 and phase 3 trials,” the spokesperson said, but didn’t mention the timeline of the trials. 

A Panacea Biotec spokesperson said that the company plans to start a phase 3 clinical trial of its dengue vaccine candidate with the Indian Council of Medical Research by the end of this year. The company had completed phase 1 and phase 2 trials of its vaccine candidate in around a hundred adults in India with promising safety and efficacy results.  

Hyderabad-based Indian Immunologicals has also completed a phase 1 clinical trials of its dengue vaccine candidate in nearly 90 participants, establishing safety, and has applied to the CDSCO for the next stage of the trials in India.

All three companies have developed their dengue vaccines after receiving virus strains from the National Institute of Health, US. 

(Edited by Gitanjali Das)

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