Making oseltamivir, the antiviral drug that has become the world's first-line defense if an influenza pandemic strikes, is a long and complicated process. But in papers published online yesterday by the Journal of the American Chemical Society, two research teams say they have found alternative synthetic routes that could make oseltamivir--better known by its brand name Tamiflu--easier to produce and perhaps affordable for developing countries too.
More than 65 countries have ordered stockpiles of oseltamivir; Roche, the Swiss company that produces it, is rapidly ramping up production capacity, and generic drug makers have started producing oseltamivir as well (ScienceNOW, 21 December 2005). But it still isn't cheap; at $12 a treatment course, the price cited by Indian generic drug maker Cipla, "developing countries still cannot stockpile in any meaningful way," says Tido von Schoen-Angerer, of Médécins sans Frontières in Berlin.
An easier synthesis could help. In one of the new studies, Harvard chemist and Nobel laureate Elias Corey describes a synthetic pathway that starts with 1,3-butadiene and acrylic acid, "two of the cheapest things you can buy," Corey says; as an additional advantage, the route avoids an intermediate, explosive step in the current production process. A team led by Corey's former student Masakatsu Shibasaki at the University of Tokyo, meanwhile, describes a somewhat longer process that also avoids the expensive starting compounds currently used to make oseltamivir.
Organic chemist K. C. Nicolaou says both pathways have "the potential to evolve into a practical manufactory process," but that Corey's synthesis in particular "is strikingly short and efficient." Yale chemist John Wood, however, says that Shibasaki's synthesis is "actually quite long" and less likely to be of practical use. Whether any new syntheses make it into production plants depends on many other things besides the price of the starting materials, he adds, including the cost of running the reactions, safety, and environmental considerations.
Shibasaki says Roche has shown an interest in his findings; David Reddy, Roche's pandemic task force leader, says that the company is "always looking at new types of technologies" but declined to discuss the two papers.
Corey says he did not patent the findings, so that they might become widely used. "My hope is that this work will save lives, especially in poor countries," he says. Still, other companies couldn't simply start using it, because patents for oseltamivir cover the compound itself, not just the way it is made, says Vid Mohan-Ram, a patent agent with Foley & Lardner LLP in Chicago. But generic drug makers could adopt the process, he says, which could drive their prices down. And an easier production route could also encourage Roche to lower its price.
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