Intravenous artesunate, the international standard of care to treat severe malaria, has finally won full FDA approval for the condition, which affects about 300 of the approximately 2,000 people diagnosed with malaria in the U.S. each year. Amivas LLC, a joint venture set up in 2016 solely to make the life-saving drug available in the U.S., won the approval following a priority review. The treatment is approved for use following a complete course of an oral antimalarial regimen.
Though approved in varying formulations as part of the World Health Organization (WHO)'s Essential Medicines list for a decade, global availability of the medicine has primarily been through a partnership of China's Guilin Pharmaceutical Co. Ltd., a Fosun Pharma company, Medicines for Malaria Venture and WHO. In the U.S., though, access has been managed by the CDC since 2007 via an expanded access investigational new drug program. With FDA approval for Amivas' product, that will soon change.
Within the next few months, the company said, it will begin making the drug available nationwide. Final pricing of the medicine has not yet been set, but "we believe the value of the product will be reflected in that price," Chief Medical Officer Bryan Smith told BioWorld. "Manufacturing and keeping the company in full compliance with all the relevant U.S. laws and regulation, that end-to-end supply chain of a critical life-saving medicine, 24-7/365 in all the corners of the country is no small task," he said.
Previously, I.V quinidine gluconate, an antiarrhythmic medication and a stereoisomer of the older antimalarial quinine, was the only parenteral drug available in the U.S that was FDA-approved for the treatment of severe malaria. However, in November 2017, the manufacturer of the product, Eli Lilly and Co., ceased production of it permanently and the remaining stocks expired on March 31, 2019, according to a CDC filing supporting expanded access to artesunate.
"This approval will now give patients more access to a life-saving drug,” said John Farley, acting director of the FDA's Office of Infectious Diseases. "Furthermore, the risk of developing severe malaria emphasizes the importance of taking medications to prevent malaria and using mosquito avoidance measures when traveling to malaria-endemic areas."
People with malaria often experience fever, chills and flu-like illness, and without appropriate treatment, they may develop severe complications, such as kidney failure, seizures, mental confusion, coma and death. Most people diagnosed with the infection in the U.S. acquire it during travel to countries with malaria.
Severe cases typically includes neurological symptoms, severe anemia, acute renal injury, acute respiratory distress syndrome or jaundice, as a large number of the patient’s red blood cells become infected by a malaria parasite, according to Amivas.
A multinational collaborative
Amivas, which Smith calls "a coalition of the willing," is a small privately held venture owned by six shareholders. The two major shareholders are Toronto-based Dalton Pharma Services, which has previously manufactured the product for the U.S. Army via the CDC, and Sydney, Australia-based Phebra Pty Ltd. As a specialist in antivenoms and other sterile injectables, Smith said Phebra brings key experience with how to market medicines that are infrequently used but must, nonetheless, be always available.
Smith, in particular, has dedicated a substantial portion of his life to making I.V. artesunate available in the U.S. He has worked for more than 15 years, including as the principal investigator for one of the last trials that the Army performed in Thailand and as the past product manager when he was still on active duty in the Army.
After becoming a co-development partner for I.V. artesunate with the U.S. Army Medical Research and Development Command's (USAMRDC) Walter Reed Army Institute of Research via a CRADA and ultimate licensure in 2017, Amivas worked together with the organization to bring it to market. Smith and his Amivas colleagues advanced the drug through a competitively bid, public-private partnership, managed in part by Major Victor Zottig, the contemporary U.S. Army Medical Material Development Activity (USAMMDA) product manager for artesunate.
The safety and efficacy of the medicine was studied in three trials, including the South East Asian Quinine Artesunate Malaria Trial (SEAQUAMAT) and the African Quinine Artesunate Malaria Trial(AQUAMAT). The two studies enrolled a total of 6,886 patients and included adults, children and pregnant women. I.V. artesunate reduced mortality by 34.7% and 22.5% vs. standard-of-care parenteral quinine during the SEAQUMAT and AQUAMAT studies, respectively. Data were also collected between January 2007 and December 2010 on 102 U.S. patients with severe or complicated malaria who were supplied I.V. artesunate under the CDC expanded access protocol.