Immunizations

New Drug For Recurring Malaria

A new drug to treat malaria has been given the green light by authorities in the United States.

The medicine is specifically for the recurring form of malaria - caused by the parasite plasmodium vivax - which makes 8.5 million people ill each year.

This type of malaria is a particular challenge to get rid of as it can remain dormant in the liver for years before reawakening many times.

Scientists have described tafenoquine as a "phenomenal achievement."

Regulators around the world will now look at the drug to see if they can recommend it for their populations.

Relapsing illness

Recurring malaria is the most common type of malaria outside Sub-Saharan Africa.

Children can be particularly at risk, getting several bouts of malaria from a single bite, missing lots of school and getting weaker each time they get the disease.

And infected people can act as unwitting reservoirs of the disease because when the parasite reawakens in their bodies a mosquito can carry that parasite on to someone else.

This can make it hard to eliminate around the world.

Now the Food and Drug Administration (FDA) in the United States has given the seal of approval to tafenoquine, a drug that can flush the parasite out of its hiding place in the liver and stop people getting it again.

It can be taken alongside another medicine to treat the immediate infection.

There is already a medication that can be used to get rid of malaria hiding in the liver called primaquine.

But unlike the single dose of tafenoquine needed, primaquine often needs to be taken for 14 days.

Some experts are concerned that many people feel better after just a few days and stop taking the pills, allowing the parasite to awaken at a later date.

Caution needed

The FDA says the drug is effective and approves it for use in the United States but points out that there are important side effects to be aware of.

For example people with an enzyme problem, called G6PD deficiency, should not take the drug as it can cause severe anaemia.

The regulator recommends people are tested for the deficiency for this before it is given - which can pose a problem in poorer areas where malaria is common.

There are also concerns that at higher doses it can be a problem for people with psychiatric illnesses.

But despite these cautions there is hope the drug, together with bed nets and other precautions, will help reduce the amount of vivax malaria in the world.

Prof Ric Price, of Oxford University, told the BBC: "The ability to get rid of the parasite in the liver with a single dose of tafenoquine is a phenomenal achievement and in my mind it represents one of the most significant advances in malaria treatment in the last 60 years."

Meanwhile Dr Hal Barron, president of research and development at GSK, the company that manufactures the drug, said it was 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."

Tafenonquine has been in existence since the 1970s but working with Medicines for Malaria, GSK has repurposed the drug so that it can be used to get rid of malaria parasites in the liver.

The next step will be for the drug to be assessed by regulators in countries where this form of malaria is a significant problem.

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GSK & MMV Announce First Single-dose Medicine For P. Vivax Malaria, Tafenoquine Prequalified By WHO And Included In WHO Guidelines

GSK plc and Medicines for Malaria Venture (MMV) announced that the World Health Organization (WHO) has awarded prequalification to tafenoquine, the first single-dose medicine for the prevention of relapse of?Plasmodium vivax?(P. Vivax) malaria. Tafenoquine, co-administered with chloroquine, is now also included in WHO's updated Guidelines for malaria, in South America, marking the first time the medicine has been recommended by WHO. This milestone is a significant step toward closing the treatment gap for P. Vivax malaria.  

The WHO prequalification and updated guidelines include both adults and children aged 2 years and older, weighing at least 10 kg. A single-dose medicine provides an opportunity to overcome challenges with adherence to the existing longer, one-two week regimen of the standard of care, which can be a challenge for patients with relapsing malaria whose symptoms improve shortly after treatment initiation.

P. Vivax is the dominant malaria parasite in most countries outside of sub-Saharan Africa, prevalent in most tropical and sub-tropical areas in the world, with children under five and migrant populations at particular risk. Among these vulnerable groups, infants and children carry a disproportionate burden, being highly vulnerable to severe disease, recurrence and anaemia. The complex lifecycle of the P. Vivax parasite?Includes a blood stage and an undetectable dormant liver stage, which can reactivate, causing repeated episodes of malaria following a single infectious bite of a mosquito carrying this parasite.

Thomas Breuer, chief global health officer, GSK,?Said: "WHO prequalification of tafenoquine opens new possibilities to positively impact and protect more lives; lives of children and vulnerable populations who continue to bear the burden of this devastating disease. Inclusion of tafenoquine in the updated Guidelines for malaria is an equally important step forward in efforts to eliminate this preventable and treatable disease. Making treatments simpler for people to take is an ambition of ours across much of our Global Health pipeline and portfolio. Alongside our partners, we remain committed to enabling affordable and equitable access to this new single-dose treatment option for those in need in malaria-endemic countries."

Martin Fitchet, chief executive officer, MMV, said: "Today marks a historic milestone in the fight against malaria. The WHO's prequalification of tafenoquine and its inclusion in the updated Guidelines for malaria is a groundbreaking advancement on the road to elimination, which will transform lives by providing a well-tolerated, effective, and single-dose cure to prevent malaria relapses in some of the world's most vulnerable communities. This achievement is a testament to the power of innovation and collaboration in global health, to bring us closer to our vision of a malaria-free world."

Tafenoquine, an 8-aminoquinoline antimalarial drug targeting the liver-stage of P. Vivax malaria, is recommended as an alternative to primaquine (3.5 mg/kg total dose) for preventing malaria relapses in children over the age of two in South America. A single dose of tafenoquine administered to P. Vivax patients who receive chloroquine treatment provides what is known as radical cure: the treatment of both the blood- and liver-stages of the disease. Tafenoquine, like all 8-aminoquinolines, has the potential to cause haemolytic anaemia in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency, therefore G6PD testing must be performed before prescribing. This is possible with the 'STANDARD' G6PD test, developed in collaboration between SD Biosensor and PATH, which provides a measure of a patient's G6PD enzyme activity levels in two minutes based on a drop of blood from a finger-prick.

WHO prequalification of medicines is crucial as it ensures that the medicine meets standards of quality, safety and efficacy, and is suitable for the target population. The prequalification programme has played a vital role in improving the access to life-saving medications used by millions in low- and middle-income countries.  

The WHO Guidelines for malaria are regularly reviewed and updated by the world's leading malaria experts under WHO's convening. This update includes a first recommendation for tafenoquine (150mg tablets and 50mg dispersible tablets) with chloroquine in South America.

WHO prequalification and Guideline inclusion follows the launch of tafenoquine in Brazil and Thailand in June this year. Approvals for tafenoquine have been granted in Australia, Brazil, Colombia, Ethiopia, Guyana, Myanmar, Pakistan, Peru, the Philippines, Thailand, Vietnam and the United States, and the drug is undergoing marketing authorisation evaluation in a number of other countries where?P. Vivax?Is endemic.  

Tafenoquine is an 8-aminoquinoline 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.  

The STANDARD G6PD test was developed in collaboration between SD Biosensor and PATH. The handheld device provides a measure of a patient's G6PD enzyme activity levels in two minutes based on a drop of blood from a finger-prick.?The Test has been approved by the Australian TGA, and by the Global Fund Expert Review Panel on Diagnostics (ERPD) and is distributed to over 30 countries.

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 readily treated with most anti-malarial treatments active against the blood-stage parasite. The current treatment (primaquine) for the dormant liver stage must be taken for 7 to 14 days to be effective, a regimen that is associated with poor compliance in unsupervised patients. The use of a medicine that targets the dormant liver forms of the parasite, co-administered with a medicine to treat the blood stage, is known as radical cure.?

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 disease is estimated to cause around 8.5 million clinical infections every year. 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 be fatal.?

GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together.

MMV is a Swiss-based not-for-profit organization working to deliver a portfolio of accessible medicines with the power to treat, prevent and eliminate malaria. Born in 1999, out of a need for greater health equity, we close critical gaps in research, development and access – working "end-to-end" to expand the use of existing antimalarials and innovate new compounds to protect public health.

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