MANILA — After a new study found a pediatric formulation of a malaria drug is effective in preventing relapse of the disease in children months after treatment, developers are hopeful this latest evidence would lead to regulatory approval of the drug. The formulation provides a simpler treatment option for children infected with the Plasmodium vivax parasite that causes malaria.
New malaria cases globally were estimated at 229 million in 2019. The majority of the cases were caused by the parasite Plasmodium falciparum, while about 3% was due to P. vivax. The disease is often treated with chloroquine or, in case of resistance to chloroquine, artemisinin-based combination therapies. But these treatments only target malaria parasites in the blood. The P. vivax parasite has a feature in which it stays dormant in the liver, which if not eliminated can cause malaria disease relapse and contribute to ongoing transmission of malaria.
This is particularly concerning for children, who are at risk of relapsing P. vivax malaria, and four times as likely as adults to be affected, Elodie Jambert, director for access and product management at Medicines for Malaria Venture, told Devex.
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“We know that in some countries, like for example in Myanmar, up to 48% of the [P.] vivax patients are happening in less than 16 years of age. And in Peru, it's even more than that, because up to 58% of the cases are happening in less than 17 years of age. So this is really affecting a lot of the pediatric population,” she said.
In 2008, MMV entered into an agreement with GlaxoSmithKline to develop tafenoquine, a single-dose treatment for P. vivax malaria relapse. A decade later, in 2018, the drug received regulatory approval in the U.S., with subsequent approvals in Australia, Brazil, and Thailand. But the approvals were limited to patients aged 16 years and older.
However their latest study, the Tafenoquine Exposure Assessment in Children, showed tafenoquine is also effective in preventing malaria relapse in children, with an efficacy rate of 95% four months after treatment. Of the 60 participants aged 2 to 15 years old, 12 experienced vomiting. According to the study, the “overall percentage of subjects reporting adverse events was similar to adult studies.”
The study found the drug should be given at different doses depending on a child’s weight. Children who weigh between 10 kilograms (22 pounds) and 20 kilos should receive 100 milligrams of the drug. Those who weigh between 20 kilos and 35 kilos should receive 200 mg. Meanwhile, those who weigh over 35 kilos should receive 300 mg of the drug, in the form of two 150 mg tablets.
MMV and GSK plan to use this latest evidence for regulatory submissions in Australia, and subsequently other malaria-endemic countries. Dr. Pauline Williams, head of global health R&D at GSK, said in a written statement to Devex that data from the TEACH study “represent an encouraging step forward in the fight against P. vivax malaria in children, providing evidence to support a paediatric formulation of tafenoquine.”
Making tafenoquine available in countries
If approved, the drug provides a simpler malaria relapse treatment option for children. At present, only one drug, Primaquine, is available in countries to treat the liver stage of the P. vivax parasite. But Primaquine requires 14 days of treatment, which poses treatment adherence challenges, said Isabelle Borghini, senior director for product development R&D at MMV.
“If you think of yourself, 14 days of treatment is long, but for a child, it's even more difficult to follow. Tafenoquine is a single dose. So that's the big advantage,” Borghini told Devex.
Apart from the regulatory approval in countries, getting recommendations from the World Health Organization will be critical in having countries include tafenoquine in their treatment guidelines. Jambert said they are having regular meetings with WHO, which is in the process of reviewing the evidence on tafenoquine.
“We are expecting to get [a] guideline released by WHO on the use of tafenoquine by the end of 2021,” she said.
In 2019, MMV also partnered with PATH on a five-year initiative called VivAccess funded by the Bill & Melinda Gates Foundation. The goal of the initiative is to help introduce and ensure access in countries of available products that would help toward the elimination of P. vivax malaria.
Jambert said a particular challenge to introducing tafenoquine, as well as primaquine, to populations is that patients need to have the enzyme glucose six phosphate dehydrogenase, or G6PD, to receive these drugs, and that requires testing. However, testing is mostly available in laboratories at hospitals.
“So this is why we are collaborating very closely with PATH … [which] has been supporting the development of a point-of-care G6PD test that can be used at different levels of the health system, in order to make sure that every patient will receive the drug in a safe manner,” she said.
Patients with G6PD enzyme deficiency could experience severe adverse reactions with the drug. Only those with >70% G6PD enzyme activity should receive tafenoquine.
While tafenoquine will be delivered on a “cost of goods” basis, introducing a new test can have additional costs. But Jambert said they are working with countries, such as Brazil, to do cost-effectiveness analysis and budget impact analysis to help them in their decision-making in adopting the treatment.
“So we will be comparing the current standard of care and the additional tools, and what this brings in terms of added value, but also in terms of additional cost,” she said.