Thursday, 11 August, 2022
HomeInfectious DiseasesGSK’s novel malaria treatment for children receives first approval

GSK’s novel malaria treatment for children receives first approval

Australian regulators have approved tafenoquine (brand name Kozenis) as an effective cure for a form of malaria in children aged 2 to 16.

The drug is a single dose of tafenoquine (brand name Kozenis), administered along with the traditional chloroquine treatment. The approval was announced by the nonprofit Medicines for Malaria Venture, which helped develop the drug, reports The New York Times.

Tafenoquine, made by GlaxoSmithKline, can cure a type of malaria caused by Plasmodium vivax, which is most common in South and Southeast Asia, South America and the Horn of Africa. The drug will be submitted for approval in nine countries, as well as to the World Health Organization (WHO), according to George Jagoe, an executive vice president at the Medicines for Malaria Venture.

Malaria is among the deadliest of infectious diseases. In 2019, there were 229m new infections and 558,000 deaths; the numbers rose during the COVID-19 pandemic, to 627,000 deaths in 2020.

Most of these deaths are in sub-Saharan Africa, home to a form of the malaria parasite called Plasmodium falciparum. A majority of the fatalities occur in children under five years old. In October, the World Health Organization (WHO) endorsed the first malaria vaccine, also made by GlaxoSmithKline, against P. falciparum.

P. vivax causes up to 5m malaria infections every year; children aged 2 to 6 are four times as likely as adults to contract the disease. The parasite is a slippery adversary that rapidly cycles through different forms in the body. In blood, the infection can cause acute symptoms of fever, chills, vomiting and muscle pains. P. vivax can also hide out in the liver, triggering relapses months or even years after the initial exposure. These episodes can lead to severe anemia, lasting brain damage and death.

“That’s the trademark of vivax malaria,” Jagoe said.

Most treatments, including chloroquine, are directed at the blood stage of the parasite, and so cannot prevent recurrence of the infection and its associated symptoms. But tafenoquine goes after the sleeper colonies in the liver. In combination with chloroquine, tafenoquine can deliver what scientists call a “radical cure”.

In July 2018, the US Food and Drug Administration (FDA) approved 300mg of tafenoquine for the radical cure of P. vivax malaria in adults and adolescents 16 years and older. Drug regulators in Australia, Brazil, Thailand and Peru followed suit with similar approvals.

The new formulation for children is given as a single small 50mg tablet dispersed in water, which is much easier for children to take than the current seven- or 14-day course of pills developed for adults — and therefore much more likely to be used.

“Now we have a tool to put a stop to the relentless relapse both for adults and children — we are one step closer to defeating this disease,” said David Reddy, chief executive of the Medicines for Malaria Venture.

Drugs for P. falciparum can be evaluated quickly, but because P. vivax causes recurrent malaria, trials require much longer follow-up. “What you’re really proving with vivax treatments like these are that six months from now, you’re not going to get a relapse,” Jagoe said.

Researchers evaluated different dosages of the drug, based on weight, for children aged 2 to 15 who weighed at least 10kg. The investigators recruited 60 children with P. vivax malaria from three sites in Vietnam and one in Colombia. The children all got a single dose of tafenoquine and a course of chloroquine administered according to local or national guidelines for the treatment of the active blood stage infection.

About 62% of the children reported some side effects, a percentage similar to that seen in adults and adolescents, the researchers reported. None of the side effects was severe, although the treatment caused vomiting in about one in five of the children.

At four months, the efficacy of the treatment in preventing recurrence was 95%, similar to the efficacy in adults and older adolescents.

Phase 2 GCK study

This was an open-label, non-comparative, multi-centre Phase 2b study to assess the pharmacokinetics (PK), safety, and efficacy of single-dose tafenoquine in the treatment of paediatric subjects with P. vivax malaria.
The primary objective was to evaluate the PK of tafenoquine in children and adolescents aged ≥2 years to <16 years with P. vivax in order to identify appropriate doses that achieve a similar exposure to that of the tafenoquine adult dose of 300 mg. Secondary objectives were to assess the safety of tafenoquine when administered to paediatric subjects with P. vivax malaria; to assess the clinical and parasitological efficacy of tafenoquine as a radical cure for paediatric subjects with P. vivax malaria when co-administered with chloroquine. Another secondary objective was to assess the PK of tafenoquine in infants aged ≥6 months to <2 years (weighing ≥5kg) with P. vivax (if data permitted).
In all, 60 paediatric subjects were recruited (median age 10 years [range 2 – 15 years]) and dosed at three sites in Vietnam and one in Colombia. All subjects received a single dose of tafenoquine and a course of chloroquine administered per local or national treatment guidelines to treat the acute blood stage of the illness. All subjects were screened for glucose-6-phosphate dehydrogenase (G6PD) deficiency prior to receiving tafenoquine and excluded from the study if they had <70% of the normal G6PD enzyme activity levels.
There were no unexpected safety findings. The overall percentage of subjects reporting adverse events was similar to previous studies in adults and adolescents 16 years and older [37/60 (62%)], with the highest-frequency adverse event being vomiting in 12 (20%) subjects. No drug-related, serious adverse events were reported. The recurrence-free efficacy rate of 95% at four months was in line with studies of tafenoquine in adults and older adolescents.

 

GlaxoSmithKline article – GSK, MMV filing for Kozenis (tafenoquine) in paediatric populations with Plasmodium vivax malaria accepted by Australian Therapeutic Goods Administration (Open access)

 

The New York Times article – Novel malaria treatment for children receives first approval (Restricted access)

 

See more from MedicalBrief archives:

 

World first as GSK’s malaria vaccine is endorsed by WHO

 

Meta-analysis: Significant effect of malaria-preventive drugs in children

 

Malaria deaths could double this year if prevention is interrupted by COVID-19

 

Kenya rolls out GSK's malaria vaccine

 

Monoclonal antibody can prevent malaria for up to 9 months — NIH trial

 

 

MedicalBrief — our free weekly e-newsletter

We'd appeciate as much information as possible, however only an email address is required.