Few diseases impact the world as profoundly as malaria. In 2016 alone, there were approximately 216 million cases of malaria worldwide with approximately 445,000 deaths. With the U.S. military suffering heavy casualties from malaria in the South Pacific during World War II, General Douglas MacArthur complained that for every division he had facing the enemy, he had another sick in the hospital, and a third in recovery. Malaria again sickened many Soldiers during the Vietnam War, where it was one of the largest sources of casualties for Americans. Malaria’s impact remains so profound today that the Department of Defense still considers it the most significant infectious disease threat to deployed U.S. Service Members.
Leading the charge to prevent malaria, Army scientists in the mid- to late-20th century participated in the development and licensure of many highly effective antimalarial drugs, notably chloroquine and primaquine. Yet, concerns about growing chloroquine resistance and primaquine contraindications required continuing research and development.
Amidst these concerns, the Experimental Therapeutics branch at the Walter Reed Army Institute of Research initiated a new antimalarial drug discovery program, enjoying early success with the discovery and synthesis of tafenoquine (Arakoda™) in 1978, a next generation analogue of primaquine.
During the 1980s, development of Arakoda™ continued at WRAIR’s Armed Forces Research Institute of Medical Science in Thailand. Preclinical studies were extremely encouraging, demonstrating the efficacy of Arakoda™ for both malaria prevention and as a cure for relapse, supporting its progression into clinical development.
Continuing in the late 1990s and early 2000s, WRAIR conducted key efficacy trials at another of its expeditionary laboratories, the U.S. Army Medical Research Unit – Kenya (now U.S. Army Medical Research Directorate – Africa). In total, 25 clinical trials with over 3,000 subjects have demonstrated Arakoda’s safety and efficacy.
During the 1990s as well, the U.S. Army Medical Materiel Development Activity joined WRAIR in development, fully taking over by 2014. USAMMDA soon brought the case for Arakoda™ licensure to the U.S. Food and Drug Administration in partnership with 60° Pharmaceuticals. In February 2018, the FDA granted a priority review designation, which allows for the accelerated review of drugs targeting neglected tropical diseases.
These decades of work culminated on Aug. 8, 2018, when the FDA approved Arakoda™ for malaria prophylaxis – the first FDA-approved prophylactic drug for malaria in more than 18 years. It is safe, effective against malaria relapse, and enjoys the advantage of less frequent dosing, weekly instead of daily, for malaria prevention.
As antimalarial drug resistance degrades the efficacy of current gold standard treatments and prophylactics, it is vitally important to maintain a robust drug pipeline to discover and develop improved, next generation malaria prevention and treatment tools. WRAIR has not only helped develop a malaria vaccine, currently in advanced clinical trials, but has participated in the development of every FDA-approved malaria prevention drug in the last 50+ years. WRAIR ET continues to search for new and improved prophylaxis and treatment drugs, and to transition next generation drug candidates into medical product development. The approval of Arakoda™ for malaria prevention represents a critical tool in global efforts to eradicate malaria.