The first new malaria cure in 60 years: GSK single dose of tanoquinoquine Kozenis

GlaxoSmithKline (GSK) and the non-profit organization Antimalarial Medicines Association (MMV) recently announced that the Australian Therapeutic Products Authority (TGA) has accepted its Category 1 application to expand single-dose Kozenis (tafenoquine) adaptation to the pediatric population in order to completely cure (prevent recurrence) of P.vivax malaria.
, the drug was approved by the TGA in 2018 to ≥ 16-year-olds.
when treating an active infection, the drug should be combined with chloroquine for a course of treatment.
the pediatric application included clinical data on a new 50mg tablet that can be dispersed in water and developed for children's use, which is more affected by malaria.
high risk of contracting the parasite in children, which is why it is important to develop a paediatric preparation called tanoquinoquine.
clinical data show that in the group of pediatric patients aged 6 months to 15 years, the treatment of single doses of tanoquinoquine is as effective as 95%.
In July 2018, single-dose krintafel was the first FDA approval for treatment of acute P.vivax infection in patients ≥16 years of age who were receiving appropriate antimalarial drugs to treat malaria caused by P. vivax.
this approval, making Krintafel the first new drug to treat parasite malaria in more than 60 years.
, single doses of tanoquinoquine have also been approved by regulators in Australia, Brazil and Thailand, and regulatory applications and reviews are progressing in other malaria-endemic countries.
currently, standard care for the recurrence of the parasite requires 7 or 14 days of treatment, and there is no age-specific paediatric formula.
this pediatric application, supported by data from a Phase 2b Clinical Study (TEACH).
the study looked at a new 50mg dispersion tablet, developed for the convenience of children, using an approved 150mg tablet.
TEACH is an open-label, non-comparative, multi-center Phase 2b study designed to evaluate pharmacogenesis (PK), safety and effracipity in single-dose estrogen-treated interstitiotic parasite pediatric patients (PK). the
study was conducted in children and adolescents aged 6 months to 15 years and weighing at least 10 kg of parasite, all of which received a single dose of thyroquinoquine and a course of chloroquine in accordance with local or national treatment guidelines for the treatment of acute blood-stage diseases.
study, patients were given different doses of tanoquinoquine based on weight: patients weighing between 10 and 20 kg were given 100mg of dispersion tablets, patients weighing 20-35kg were given 200mg dispersion tablets, and patients weighing >35 kg were given 300mg (2 tablets of 150mg tablets).
Now no patients were included in the minimum weight group (≥6 months to <2 years old, weighing ≥5 kg to ≤10 kg), the pharmacodynamics (PK) model data from the TEACH study showed that children in that weight group should receive a dose of 50 mg of estanoquinol.
the study, which included 60 patients, showed that 95 percent of the patients in the four-month follow-up did not relapse, and that the relapse was effectively consistent with his studies in adult and adolescent (≥16-year-old) patients.
, except for vomiting after early administration, safety was consistent with previous clinical studies and no serious adverse drug-related events were reported.
malaria (Inter-Day Malaria) has a significant impact on public health and the economy, mainly in South-East Asia, South-East Asia, Latin America and the Horn of Africa.
estimates that the disease causes about 7.5 million clinical infections each year.
clinical characteristics of P.vivax include fever, chills, vomiting, discomfort, headache and muscle pain, which in some cases can lead to severe malaria and death.
the prevalence of parasites among children aged 2-6 years has peaked.
addition, children are four times more likely to be affected than adults, and Plasmodium parasite is a complex life form whose life cycle spans humans and mosquitoes.
after being bitten by an infected mosquito, the parasite infects the blood and causes an acute malaria attack.
parasite can also hibernate (sleep) in the liver and periodically reactivate in the liver, leading to a recurrence of parasite malaria.
, a daily malaria parasite infection can lead to multiple malarias without new mosquito bites.
these relapses can occur weeks, months, or even years after the initial infection.
, which sleeps in the liver, cannot be treated with most antimalarial drugs that treat the blood-stage malaria parasite.
is used in combination with the currently available blood-stage antimalarial drug, such as chloroquine, for the liver sleeper of the parasite, known as root therapy.
until recently, 8-aminoquinoline primaquine was the only drug approved for liver hibernation to prevent recurrence.
, however, the treatment plan of the 14-day course of treatment is often associated with poor compliance, resulting in reduced efficacy.
Tafnoquine was first synthesized in 1978 by scientists at the Walter Reed Army Research Institute (WRAIR) in the United States, an 8-aminoquinoquine derivative with anti-japanese malaria life cycle activity, including inter-day malaria parasites in sleeping forms in the liver.
GSK and MMV reached a strategic partnership back in 2008, and after a decade of hard work, a single dose of tafenoquine was first awarded to the FDA in July 2018 for ≥16-year-olds and adolescents.
, the drug was regulatoryly approved in Australia, Brazil and Thailand.
review is under way in other malaria-endemic countries.
all approvals are based on data on the efficacy and safety of the Inter-Day Malaria Rooting Global Integrated Clinical Development Project, which is conducted in nine malaria-endemic countries and supports the overall positive benefit risk profile of Klintafel.
is needed in combination with chloroquine to treat the blood and liver stages of acute parasite infections (called root therapy).
patients must be tested for deficiency of glucose-6-phosphate dehydrogenase (G6PD), which helps protect red blood cells, before taking tanoquine or burmaquine.
patients with G6PD enzyme deficiency may experience serious adverse reactions during the course of root-and-drug therapy, such as hemolytic anemia, and only 70% of patients with G6PD enzyme activity should receive histnoquine treatment.
original origin: GSK, MMV filing for Kozenis (tafenoquine) in paediatric populations with Plasmodium vivax malaria accepted by Australian Therapeutic Goods Administration