A recent article in Science illustrates a number of points about drug development and scale-up. It's about artemisinin, the antimalarial. Peter Seeberger, a German professor of chemistry (Max Planck-Potsdam), has worked out what looks like a good set of conditions for a key synthetic step (dihydroartemisinic acid to artemisinin), and would like to see these used on large scale to bring the cost of the drug down.
That sounds like a reasonably simple story, but it isn't. Here are a few of the complications:
But Seeberger's method has yet to prove its mettle. It needs to be scaled up, and he can't say how much prices would come down if it worked. Using it in a large facility would require a massive investment, and so far, nobody has stepped up to the plate. What's more, pharma giant Sanofi will open a brand-new facility later this year to make artemisinin therapies based on Amyris's technology: yeast cells that produce a precursor of the drug. Although Seeberger says his discovery would complement that process, Sanofi says it's too late now to adopt it.
The usual route has been to extract arteminisin from its source, Artemisia annua. That's been quite a boom-and-bust cycle over the years, and the price has never really been steady (or particularly low, either). Amyris worked for some years to engineer yeast to produce artemisinic acid, which can then be extracted and converted into the final drug, and this is what's now being scaled up with Sanofi-Aventis.
That process also uses a photochemical oxidation, but in batch mode. I'm a big fan of flow chemistry, and I've done some flow photochemistry myself, and I can agree that when it's optimized, it can be a great improvement over such batch conditions. Seeberger's method looks promising, but Sanofi isn't ready to retool to use it when they have their current conditions worked out. Things seem to be at an impass:
But what will happen with Seeberger's discovery is still unclear. Sanofi's plant is about to open, and the company isn't going to bet on an entirely new technique that has yet to prove that it can be scaled up. In an e-mail to Science, the company calls Seeberger's solution “a clever approach,” but says that “so far the competitivity of this technique has not been demonstrated.”
The ideal solution would be if other companies adopt the combination of Amyris's yeast cells and Seeberger's method, [Michigan supply-chain expert] Yadav says; “then, the price for the drugs could go down significantly.” But a spokesperson for OneWorld Health, the nonprofit pharmaceutical company that has backed Sanofi's project, says there are no plans to make the yeast cells available to any other party.
Seeberger himself is trying to make something happen:
On 19 April, Seeberger invited interested parties to a meeting in Berlin to explore the options. They included representatives of Artemisia growers and extractors, pharmaceutical companies GlaxoSmithKline and Boehringer Ingelheim, as well as the Clinton Foundation, UNITAID, and the German Agency for International Cooperation. (The Bill and Melinda Gates Foundation canceled at the last minute.) None of the funders wanted to discuss the meeting with Science. Seeberger says he was asked many critical questions—“But then the next day, my phone did not stop ringing.” He is now in discussions with several interested parties, he says.
As I say, I like his chemistry. But I can sympathize with the Sanofi people as well. Retooling a working production route is not something you undertake lightly, and the Seeberger chemistry will doubtless need some engineering along the way to reach its potential. The best solution seems to me to be basically what's happening: Sanofi cranks out the drug using its current process, which should help a great deal with the supply in the short term. Meanwhile, Seeberger tries to get his process ready for the big time, with the help of an industrial partner. I wish him luck, and I hope things don't stall out along the way. More on all this as it develops over the next few months.