At the turn of the millennium, drugs derived from the sweet wormwood plant—artemisinins—dramatically improved malaria care just as older medicines were failing because the parasite had evolved resistance. George Jagoe of the Medicines for Malaria Venture says the deaths seen in the late 1990s and early 2000s—about 2 million a year—were a direct result of drug failure, and that no one wants to face that situation again.
Artemisinins have since saved millions and remain the global backbone of malaria treatment. But worrying signs have emerged that the parasite is developing resistance to artemisinins, first identified in Southeast Asia and now spreading across parts of Africa. That has driven calls for new drugs that attack the parasite in different ways.
After more than two decades of research, a promising alternative is close to reality. GanLum, a combination of a new drug (ganaplacide) and an older partner (lumefantrine), was reported to be more than 97% effective in clinical trials conducted in 12 African countries. Investigators presented the results at the American Society for Tropical Medicine and Hygiene meeting in Toronto. Kasturi Haldar, a longtime malaria researcher, called the development “a big deal” and “pretty timely.”
Ganaplacide was discovered by scientists at Novartis after screening more than 2.3 million molecules. Laboratory studies show it disrupts the parasite’s ability to survive inside human red blood cells, kills all known forms of the parasite—including strains with mutations linked to artemisinin resistance—and attacks the stage responsible for transmission. Blocking transmission as well as treating infection is a major advantage, Haldar says, because it can help prevent the spread of resistant parasites.
The clinical program enrolled more than 16,000 people age 2 and up with malaria across a dozen African countries. Participants were randomized: half received GanLum over three days, the other half received the current artemisinin-based standard of care. Both regimens performed about equally well, with GanLum slightly ahead. Side effects were similar—nausea and diarrhea were common in both groups—but vomiting was reported more frequently among those on GanLum.
Experts not involved in the trial say the new drug could be a vital tool if artemisinin-based therapies begin to fail more widely. David Fidock of Columbia University notes that partial artemisinin resistance has been spreading aggressively in parts of Africa and that new drugs will be needed should resistance lead to treatment failure.
GanLum still must clear additional regulatory hurdles before broad use; the study team estimates about a year and a half for the next steps. Even if approved, GanLum is unlikely to immediately replace artemisinin combinations everywhere, since those drugs still work in many locations. But GanLum could be deployed where artemisinin responsiveness is lacking, helping to preserve the effectiveness of both treatments and to avoid the surge in deaths historically seen when resistance overwhelms available tools.
