FDA Approves Krintafel (tafenoquine) for the Radical Cure of Plasmodium vivax Malaria

 GSK and Medicines for Malaria Venture (MMV) today announced that the United States Food and Drug Administration (FDA) has approved, under Priority Review, single-dose Krintafel (tafenoquine) for the radical cure (prevention of relapse) of Plasmodium vivax (P. vivax) malaria in patients aged 16 years and older who are receiving appropriate antimalarial therapy for acute P. vivax infection.Dr. Hal Barron, Chief Scientific Officer and President of Research and Development, GSK, said: “Today’s approval of Krintafel, the first new treatment for Plasmodium vivax malaria in over 60 years, is a significant milestone for people living with this type of relapsing malaria. Together with our partner, Medicines for Malaria Venture, we believe Krintafel will be an important medicine for patients with malaria and contribute to the ongoing effort to eradicate this disease.”

Dr. David Reddy, Chief Executive Officer of MMV said: “The US FDA’s approval of Krintafel is a major milestone and a significant contribution towards global efforts to eradicate malaria. The world has waited decades for a new medicine to counter P. vivax malaria relapse. Today, we can say the wait is over. Moreover, as the first ever single-dose for this indication, Krintafel will help improve patient compliance. We are proud to have worked side-by-side with GSK for more than a decade to reach this point. Our focus is now on working to ensure the medicine reaches the vulnerable patients that need it most.”

The approval was based on efficacy and safety data from a comprehensive global clinical development P. vivax radical cure programme designed in agreement with the FDA. Thirteen studies in healthy volunteers and patients directly supported the programme. The primary evidence for the clinical efficacy and safety of the 300mg single-dose, to which more than 800 subjects were exposed, was provided by three randomised, double-blind studies: DETECTIVE Part 1 and Part 2 (TAF112582) and GATHER (TAF116564). The results of the two phase III studies were announced in June 2017. The submission included data analysed from a total of thirty-three studies involving more than 4,000 trial subjects exposed to the 300mg single-dose and other doses of tafenoquine.With the approval of Krintafel, the FDA awarded GSK a tropical disease priority review voucher. The tropical disease priority review voucher programme is designed to encourage development of new drugs and biological products for prevention and treatment of certain neglected tropical diseases affecting millions of people throughout the world.The new drug application (NDA) was submitted by GSK to the FDA in November 2017 and a regulatory submission was also made to the Australian Therapeutics Good Administration (TGA) in December 2017. A decision from the TGA is awaited. Approvals by FDA and TGA will be informative to other regulatory agencies for their own approval process in malaria-endemic countries where tafenoquine will be provided as a not-for-profit medicine to maximise access to those who need it most.

About Krintafel (tafenoquine)

Krintafel is an 8-aminoquinoline derivative with activity against all stages of the P. vivax lifecycle, including hypnozoites. It was first synthesised by scientists at the Walter Reed Army Institute of Research in 1978. GSK’s legacy in the research and development of tafenoquine as a potential medicine for malaria commenced over 20 years ago. In 2008, GSK entered into a collaboration with the not-for-profit drug research partnership, MMV, to develop tafenoquine as an anti-relapse medicine for patients infected with P. vivax. The tafenoquine clinical programme is part of GSK’s global health programme aimed at improving healthcare for vulnerable populations.

Important Safety Information

CONTRAINDICATIONS

Krintafel should not be administered to:

• patients who have glucose-6-phosphate dehydrogenase (G6PD) deficiency or have not been tested for G6PD deficiency
• patients who are breastfeeding a child known to have G6PD deficiency or one that has not been tested for G6PD deficiency
• patients who are allergic to tafenoquine or any of the ingredients in Krintafel or who have had an allergic reaction to similar medicines containing 8-aminoquinolines.

WARNINGS AND PRECAUTIONS

Hemolytic Anemia Breakdown of red blood cells (hemolytic anemia) may occur in a patient who has G6PD deficiency. G6PD testing must be performed before prescribing Krintafel. Treatment with Krintafel is contraindicated in patients with G6PD deficiency or unknown G6PD.

G6PD Deficiency in Pregnancy or Lactation The use of Krintafel during pregnancy may cause hemolytic anemia in a G6PD-deficient fetus. Krintafel is not recommended during pregnancy. Females of reproductive potential should avoid pregnancy or use effective contraception for 3 months after the dose of Krintafel.

A G6PD-deficient infant may be at risk for hemolytic anemia from exposure to Krintafel through breast milk. Infant G6PD status should be checked before breastfeeding begins. Krintafel is contraindicated in breastfeeding women when the infant is found to be G6PD deficient or the G6PD status of the infant is unknown. A woman with a G6PD-deficient infant or if the G6PD status of the infant is not known should not breastfeed for 3 months after the dose of Krintafel.

Methemoglobinemia Asymptomatic elevations in methemoglobin have been observed in the clinical trials of Krintafel. Physicians should carefully monitor individuals with nicotinamide adenine dinucleotide (NADH)-dependent methemoglobin reductase deficiency and advise patients to seek medical attention if signs of methemoglobinemia occur.

Psychiatric Effects Serious psychiatric adverse reactions have been observed in patients with a previous history of psychiatric conditions at doses higher than the approved dose. The benefit of treatment with Krintafel must be weighed against the potential risk for psychiatric adverse reactions in patients with a history of psychiatric illness. Due to the long half-life of Krintafel (15 days), any signs or symptoms of psychiatric adverse reactions that may occur could be delayed in onset and/or duration.

Hypersensitivity Reactions Serious hypersensitivity reactions (e.g., angioedema) have been observed with administration of Krintafel. Due to the long half-life of Krintafel (15 days), any signs or symptoms of hypersensitivity adverse reactions that may occur could be delayed in onset and/or duration. Physicians should advise patients to seek medical attention if signs of hypersensitivity occur.

ADVERSE REACTIONS

The most common adverse reactions (≥5%) observed for Krintafel in clinical trials were dizziness, nausea, vomiting, headache, and decreased hemoglobin.

DRUG INTERACTIONS

Physicians should avoid coadministration of Krintafel with drugs that are substrates of organic cation transporter-2 (OCT2) or multidrug and toxin extrusion (MATE) transporters (for example, dofetilide, metformin).

To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

GSK - a science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. For further information please visit www.gsk.com

Medicines for Malaria Venture (MMV) - MMV is a leading product development partnership (PDP) in the field of antimalarial drug research and development. Its mission is to reduce the burden of malaria in disease-endemic countries by discovering, developing and facilitating delivery of new, effective and affordable antimalarial drugs.

Since its foundation in 1999, MMV and partners have built the largest portfolio of antimalarial R&D and access projects ever assembled, and brought forward seven new medicines that are already saving lives. MMV's success is based on its extensive partnership network of around 160 active pharmaceutical, academic and endemic-country partners in more than 55 countries.

MMV's vision is a world in which innovative medicines will cure and protect the vulnerable and under-served populations at risk of malaria, and help to ultimately eradicate this terrible disease.

Cautionary statement regarding forward-looking statements

GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D 'Principal risks and uncertainties' in the company's Annual Report on Form 20-F for 2017.

Source: GSK

Posted: July 2018