Tafenoquine is an investigational medicine in phase III development. If approved, it would be the first new medicine to cure relapsing malaria in over 60 years. Tafenoquine is being developed as a single dose to prevent malaria relapse, to be administered alongside a standard 3-day ACT to cure the immediate infection.
Tafenoquine is a member of the same chemical family as primaquine; both are associated with a risk of haemolytic side-effects in patients lacking the enzyme glucose-6-phosphate dehydrogenase (G6PD). GSK is working with PATH to accelerate the development of a G6PD pointof-care diagnostic test, so that patients’ G6PD status can be tested to determine if tafenoquine or primaquine can be safely administered.
We asked Dr Wiweka Kaszubska and Dr JP Kleim to provide an update on the phase III programme. They also explain the advantages of having obtained a ‘Breakthrough Therapy’ regulatory designation from the US Food and Drug Administration (FDA) and discuss how they are collaborating with other partners to ensure access to the medicine.
1. What is exciting about tafenoquine as a future antimalarial?
WK: Tafenoquine is a game-changer in many ways; if approved by regulators, it will be the first medicine indicated for relapse prevention of P. vivax malaria since the 1950s. It is the only tool in the malaria pipeline for the elimination and eradication of P. vivax malaria that acts on the ‘hidden reservoir’ of parasites in the liver. Furthermore, to improve patient compliance we are developing tafenoquine as a singledose treatment that could potentially transform the treatment approach for relapsing malaria.
2. How is the phase III programme progressing?
JPK: Tafenoquine has been in phase III clinical development since April 2014 in eight P.vivax malaria-endemic countries investigating a single dose of 300 mg; this dose was selected based on results of phase II dose-ranging studies. We expect to finish recruitment for the phase III programme in 2016.
3. What are the implications of the US FDA designation of Breakthrough Therapy and how is engagement with other international regulatory authorities progressing?
JPK: The Breakthrough Therapy Designation was enacted as part of the 2012 FDA Safety and Innovation Act (FDASIA). The goal is to expedite the development and regulatory review of designated drugs to treat serious or life-threatening medical conditions when the drug may offer substantial improvement over available therapies.
Additionally, this designation affords us more intensive guidance from the FDA on tafenoquine’s clinical development plan. Stringent regulatory review of a tafenoquine dossier by the FDA would precede planned subsequent registrations in malaria-endemic countries.
4. How is the patient access plan progressing and how is each partner contributing?
WK: MMV is working with GSK, PATH and other groups to develop the access plan well in advance. The partners meet quarterly to make sure the plans are aligned and will be delivered in concert. GSK has been in a partnership with us for a number of years and is responsible for the overwhelming majority of the drug development work; MMV has supported GSK strategically, tactically and financially. The Bill & Melinda Gates Foundation, in addition to sponsoring the new diagnostic test, provides regulatory and patient access expertise through their contacts in the field.
5. How is the G6PD pointof-care test progressing in partnership with PATH?
JPK: The potential benefit of using a new medicine versus the associated risks of haemolytic side-effects is at the forefront of our minds. The goal of the PATH/GSK collaboration is to have at least one diagnostic test suitable for use with tafenoquine at the time of its potential approval. We are currently working with two diagnostic companies to develop their differing technologies and to assess the ability of each to fulfil the specification that we believe would be required.