I wrote a few months ago about the Drugs for Neglected Diseases Initiative (DNDI) and how some people have pointed to its low costs as a new model for drug discovery. I wasn’t convinced. Now there’s a long article at Nature News (update: link fixed) about the DNDI and how its low costs could be a new model for drug discovery. I’m not convinced.
As pointed out in that previous post, the initiative, for the most part, is repurposing drugs that were discovered and at least partially developed by someone else, using someone else’s time, money, expertise and infrastructure. That makes perfect sense – they’re trying, after all, to get to a human therapeutic in the shortest amount of time and without spending huge amounts of money. But it doesn’t mean that everyone else can do it that way. The article itself says that the DNDI claims that these in-kind contributions account for only 10 to 20% of its expenses, but I find that hard to work out, and would like to see the numbers to verify that figure. It’s not easy, for example, to account for the savings of (in the case of fexnidazole) knowing to look at nitroimidazoles because plenty of people have already looked at them as similar drugs, or to assign a dollar value to “having a big set of proprietary antiinfective screening compounds made available to us when we didn’t have any”.
That’s not a made-up example. My post last December went into the history of most of the compounds that this current article talks about, but there’s another one to mention: SCYX-7158 for sleeping sickness. Here’s a recent article on the project, which looks to be going well so far. But where did this one come from? Well, that four-letter code, which the Nature article doesn’t explain, refers to an actual small drug company called Scynexis. Here’s an article from a year earlier on the screening efforts that led to the discovery of the lead molecule, and you’ll notice that the authors are both academic researchers as well as people from Scynexis (a contract research company in North Carolina) and from another company, Anacor (in Palo Alto). It was, in fact, a screening library from Anacor of proprietary boron-containing compounds that led to the hit, and the compound is also known as AN5568.
How did Anacor come to have a big set of such compounds? Why, they raised money from investors to synthesize, purify, curate and screen them, because they were going to make money by selling the resulting drugs to patients. They in fact signed a deal with GSK (for money) for one of their compounds as an antibiotic candidate, which after several years ran into some problems in the clinic, as new compounds often do. Anacor, though, had several other compounds in its development pipeline, and was, in fact, acquired by Pfizer in June – for money, needless to say, $5.2 billion dollars of the stuff. Scynexis, for its part, is able to do what it does because they charge their own clients money for their services, although their work for the DNDI seems to have been largely or entirely pro bono.
I keep emphasizing all that money stuff because of comments like these from Bernard Pécoul of DNDI:
“I hope we provide lessons that can be used by others,” says Pécoul. But companies won’t simply adopt the DNDi’s methods, because they do not generate profit. The investors who keep firms alive are concerned with the bottom line. Pécoul says that a transformation would require government involvement and a reorganization of the development process. It would need a system to prioritize what treatments are needed and which companies and organizations could collaborate; and it would require forethought about how the final products would reach those in need. It means shifting away from profit-based incentives to things such as prizes and government funding. Today’s profit-driven approach is not only expensive, Pécoul says, it fails huge swathes of the population.
Ah, “a system”, one that would “require forethought”. There we go. Wiser heads than ours will work that sort of thing out, no doubt at some sort of central planning bureau, where far-seeing administrators will pick the “companies” – quaint term – that will be assigned to work on the projects. All will be well – or all would be well, if those pesky investors, concerned with the bottom line, would just get out of the way.What I think that Pécoul is missing is that the DNDI’s methods exist because of those investors. These methods presuppose that other people have already put their money into things that the DNDI can use. Every single drug that the initiative is developing – and they’re all worthwhile – piggybacks on other people’s quest for profit. I hate to be so crass about it, but there’s no way around that fact. Other people bought the concrete and rebar, other people were paid to pour the stuff into forms and lay the flooring, use of the resulting stairs was donated to the DNDI, and its director claims to have found a cheaper way to get to the second floor. And he’s up there wagging his finger at those of us who are still hauling around the construction equipment.
Now, market failures exist, and tropical diseases are definitely one of them. I think that the DNDI is a worthwhile thing and that they’re doing good in the world. I would donate some of my own efforts to their work if the opportunity arose. But that donation would be made because I could afford it, just as the donations from the rest of the drug industry are being made because we can afford to do so, which is because we make money and have used this money to discover an awful lot about human drug research. I very much hope that the DNDI gets its compounds to those who need them – but to pretend that they’re showing us the way beyond the grubby profit motive is just mistaken.