For the first time in more than 18 years, the FDA has approved a new drug for malaria prevention. Washington-based 60 Degrees Pharmaceuticals LLC (60P), which got a green light to market Arakoda (tafenoquine) tablets for adults, said the approval marks the culmination of more than 30 years of R&D with the U.S. Army Medical Research and Materiel Command, starting with the discovery of tafenoquine at the Walter Reed Army Institute of Research.

Trials of the drug in more than 3,100 participants found the once-weekly prophylactic to be effective against both of the major types of malaria, Plasmodium vivax and Plasmodium falciparum, killing the parasites in both the blood and liver and safe in use of the drug for up to six months. That broad species coverage means the prescribing decision is easier, from a geographic standpoint, 60P founder and CEO Geoff Dow told BioWorld.

In most of Africa, there's very little P. vivax, while in parts of southeast Asia there's growing resistance to some of the most commonly used drugs. "For the travel medicine physician, we anticipate that the prescribing decisions will be more straightforward, while for the patients, compliance will be easier because it's once a week," Dow said.

60P is targeting a U.S. commercial launch for the product early next year, though it is still considering whether to hire on help for that effort. While pricing for the drug has yet to be set, it will be benchmarked to existing alternatives based on the duration of the regimen, Dow said.

The approval came less than two weeks after the FDA's Antimicrobial Drugs Advisory Committee voted 11-2 in support of Arakoda's efficacy and 9-4 in support of its safety. (See BioWorld, July 27, 2018.)

The malaria market

Tafenoquine (TQ), an 8-aminoquinoline, is a synthetic analogue of the antimalarial primaquine. It was first synthesized by scientists at the Walter Reed Army Institute of Research in 1978 and has since been studied in more than 30 clinical trials over the past three decades. The drug has been shown to work against the major malaria parasites and all stages of the parasites' lifecycle and to have very little potential to trigger the development of resistance. (See BioWorld, July 25, 2018.)

Among the trials bolstering that claim were initial safety trials, as well as important field studies, including a comparative study with mefloquine conducted during a deployment of the Australian military in East Timor during peacekeeping operations there in 2000 and 2001. Placebo-controlled studies have also been conducted in Africa and southeast Asia.

60P began working with the U.S. Army on an FDA application for approval in 2014. Much of that effort has consisted of statistical programming to get clinical data coded in the right way for the FDA application and research to determine what regulators would focus on in their review of the drug. But, even after that work, it needed to sponsor a challenge study of its own, inoculating volunteers with malaria parasites to compare tafenoquine to placebo to fill in important confirmatory data for the FDA application.

Arakoda is the second TQ drug approved this summer, following July's approval of Krintafel (tafenoquine), a medicine developed by Glaxosmithkline plc and its partner, Medicines for Malaria Venture, for the prevention of relapse in patients infected with P. vivax who are already receiving antimalarial therapy. That drug is taken as a 300-mg single dose. With the parasite estimated to cause around 8.5 million clinical infections every year, GSK spokeswoman Ashley Mahoney told BioWorld that her company is not currently investigating tafenoquine as a prophylactic treatment.

Because GSK was the first to gain approval for its tafenoquine, it earned a tropical disease priority review voucher from the FDA.

The approved regimen for Arakoda's preventive mission, by contrast, consists of subjects receiving a loading dose of 200 mg once daily for three days before traveling to an area with malaria, followed by 200-mg maintenance weekly doses while in the area, and then a single 200-mg dose in the week after leaving the area. It can be dosed continuously for up to six months, although 60P is currently studying safety up to dosing through 12 months.

All patients taking Arakoda (and Krintafel) must be tested for glucose-6-phosphate dehydrogenase deficiency prior to prescribing due to the risk of hemolytic anemia. Dow said that, in the U.S., such testing is fairly routine, but in malaria-endemic countries where there is less infrastructure, access to routine lab tests is harder. To help surmount that challenge, GSK has worked with the nonprofit PATH to develop a point-of-care G6PD test.

Arakoda will join an active market for malaria prevention drugs, led by GSK's Malarone (atovaquone plus proguanil) and its generics. Other products sharing the market include doxycycline, mefloquine and its generic forms, primaquine, and chloroquine, according to the CDC.

Dow said the company will initially focus its efforts on travelers in the U.S., Australia and Canada. In September 2017, it submitted an application for approval to the Australian Therapeutic Goods Administration. Meanwhile, with the U.S. Arakoda approval secured, Dow and his team can turn their attention more fully to pursuing the initial opportunities the company has started to chase, in developing a treatment for dengue fever.

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