Single-dose Kozenis (tafenoquine) approved for children with Plasmodium vivax malaria by Australian Therapeutic Goods Administration

Geneva 14 March 2022. Medicines for Malaria Venture (MMV) today announce that the Australian Therapeutic Goods Administration (TGA) has approved the use of single-dose Kozenis (tafenoquine) in children aged 2 years and above in combination with chloroquine for the radical cure (prevention of relapse) of Plasmodium vivax (P. vivax) malaria. 

The approval includes a novel, 50 mg tablet that can be dispersed in water and which was developed by GSK in partnership with MMV to facilitate use in children, who are disproportionately affected by the disease.

“We are proud to have worked with GSK to develop this child-friendly treatment and are thrilled by today’s announcement. P. vivax malaria is particularly dangerous for young children for whom repeated relapses can lead to cumulative severe anaemia and, in some cases, be fatal. Today, 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 Dr David Reddy, Chief Executive Officer, MMV.   

Dr Thomas Breuer, Chief Global Health Officer, GSK, said: “We are delighted by this approval of Kozenis for paediatric populations. This achievement is testament to the dedication of GSK scientists and our partner MMV, who all worked tirelessly so the first relapse prevention treatment for P. vivax malaria in more than 60 years can be made available to the most vulnerable in society, our children.”

The submission was supported by a Phase 2b clinical study (TEACH) that evaluated dosages of tafenoquine based on weight for children between the age of 2 years, and weighing at least 10 kg, and up to 15 years. 

Kozenis is a single-dose treatment for the prevention of relapse of P. vivax and was approved for people aged 16 years and older by the TGA in 2018. It should be used with a course of chloroquine to treat the active blood stage infection, thereby achieving radical cure.

The current standard of care for prevention of P. vivax relapse requires a 7- or 14-day course of treatment with a drug called primaquine and at present there are no quality-assured, age-specific paediatric formulations marketed. 

P. vivax malaria is estimated to cause between 4.1 and 5.1 million clinical infections every year, and poses a disproportionate burden for children aged 2 to 6 years who are four times as likely as adults to be infected.    The clinical features of P. vivax malaria include fever, chills, vomiting, malaise, headache and muscle pain, and in some cases, can lead to severe malaria and death.   P. vivax malaria infections also impact a child’s development and educational progress with evidence showing that children who experience repeated P. vivax infections are likely to suffer from physical and cognitive impairment.  

Further regulatory submissions are planned in malaria-endemic countries for paediatric indications for tafenoquine.
 

About TEACH (TAF113577)

Tafenoquine Exposure Assessment in CHildren (TEACH) 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 pharmacokinetics 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 approved 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 total, 60 paediatric subjects with P. vivax malaria were recruited (median age 10 years [range 2 – 15 years]) and dosed at three sites in Vietnam and one site 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 (62%) of subjects reporting adverse events was similar to previous studies with tafenoquine in adults and adolescents aged 16 years and older, with the highest-frequency adverse event being vomiting in 20% of subjects. No drug-related, serious adverse events were reported. The recurrence-free efficacy rate of 95 percent at four months was in line with studies of tafenoquine in adults and older adolescents. 

Further information is provided in the attachment.