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 dispersible 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 anemia 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 pediatric 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 pediatric 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 pediatric indications for tafenoquine.
Tafenoquine, developed by GSK and MMV, was first approved by the US Food and Drug Administration for the radical cure (prevention of relapse) of P. vivax malaria in July 2018 for use in adults and adolescents ≥16 years old. It was subsequently approved by regulators in Australia, Brazil, Thailand and Peru.
Regulatory applications are being progressed in other malaria-endemic countries. All approvals are based on efficacy and safety data from a comprehensive global clinical development program for P. vivax radical cure, conducted in nine malaria-endemic countries, which supported an overall positive benefit–risk profile for the use of the product.
Tafenoquine should be co-administered with chloroquine to treat both the blood- and liver-stages of acute P. vivax malaria infections (known as radical cure). Before taking tafenoquine, patients must be tested for deficiency of a specific enzyme known as glucose-6-phosphate dehydrogenase (G6PD), which helps protect red blood cells. Patients with a G6PD enzyme deficiency could have severe adverse reactions, like hemolytic anemia, during treatment with the 8 aminoquinoline class of drugs (such as tafenoquine and primaquine) and only patients with G6PD enzyme activity >70% of normal should receive tafenoquine.
P. vivax malaria has a significant public health and economic impact, primarily in South-Asia, South-East Asia, Latin America and the Horn of Africa. The Plasmodium parasite is a complex organism with a lifecycle spanning both humans and mosquitoes. After an infected mosquito bite, the P. vivax parasite infects the blood and causes an acute malaria episode. It also has the ability to lie dormant in the liver (in a form known as hypnozoite), from where it periodically reactivates to cause relapses of P. vivax malaria. Hence, a single P. vivax infection can give rise to multiple episodes of malaria in the absence of a new mosquito bite. These relapses can occur weeks, months or even years after the initial infection. The dormant liver forms of the parasite cannot be treated with most antimalarial treatments active against the blood-stage parasite.
The co-administration of a blood-stage antimalarial such as chloroquine and a medicine that targets the dormant liver forms of the P. vivax parasite is known as radical cure.
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