Sanofi and nonprofit drug developer OneWorld Health said today they launched large-scale production of the key ingredient in the most effective malaria vaccines, using a synthetic biology technology developed over almost a decade by the partners with Amyris and its co-founder, a University of California, Berkeley, professor.
Sanofi and OneWorld Health, a drug-development affiliate of nonprofit PATH, said they intend to produce 35 tons of semisynthetic artemisinin this year, and an average 50 to 60 tons per year starting in 2014, at Sanofi’s Garessio site in Italy.
That corresponds to between 80 and 150 million artemisinin-based combination therapies (ACTs), identified by the World Health Organization in 2005 as the most effective first-line treatment available for uncomplicated malaria.
"The production of semisynthetic artemisinin will help secure part of the world's supply and maintain the cost of this raw material at acceptable levels for public health authorities around the world and ultimately benefit patients," said Robert Sebbag, M.D., vp of Access to Medicines at Sanofi, said in a statement. "This is a pivotal milestone in the fight against malaria."
By producing semisynthetic artemisinin, Sanofi and OneWorld Health said, they account for inconsistencies in botanical supplies of the strain of yeast derived from the sweet wormwood plant Artemisia annua. The partners say that maintaining several sources of artemisinin will contribute to a more stable price, and ultimately ensure greater availability of treatment for people with malaria.
The semisynthetic artemisinin will be made by producing artemisinic acid through fermentation carried out by Bulgaria’s Huverpharma, followed by a synthetic transformation of the artemisinic acid into artemisinin via photochemistry by Sanofi. The artemisinin is chemically transformed into the active antimalarial drug artesunate, then combined with another antimalarial drug to create the antimalarial ACT—a process that partners say reduces the chance that the malaria parasite will develop resistance to artemisinin.
The process uses technology discovered by Jay D. Keasling, Ph.D., professor of chemical engineering at UC Berkeley. Dr. Keasling—who is also associate director for biosciences at Lawrence Berkeley National Laboratory, and CEO of the Joint Bioenergy Institute—discovered that implanting wormwood and yeast genes into bacteria made the bacteria produce a chemical that could be chemically converted to artemisinin.
In 2006, further research turned up another gene that, when inserted into yeast with the earlier genes, allowed Dr. Keasling and colleagues to synthesize small amounts of artemisinic acid. Using Dr. Keasling’s synthetic biology techniques, Amyris added that gene to yeast along with other plant genes to increase artemisinic acid production by a factor of 15—at which point Sanofi became interested.
Dr. Keasling and colleagues at Amyris—a company he cofounded in 2003 to commercialize the discovery—have published in Nature the sequence of genes they introduced into the yeast. The paper was posted online April 10 and will appear in Nature’s April 25 print issue.
OneWorld Health shepherded the drug's development from Dr. Keasling's UC Berkeley lab to Amyris for scale-up, then to Sanofi for production. OneWorld’s work was funded by two grants totaling $53.3 million from the Bill & Melinda Gates Foundation.
According to Sanofi, the price of the vaccine will be kept low for developing countries through a no-profit, no-loss production model. Dr. Keasling said UC Berkeley helped make that possible by pushing for royalty-free licensing of the process to Sanofi, which agreed in return to sell artemisinin at cost.