John LaMattina on the new NIH drug discovery center

There's a post by ex-Pfizer research chief John LaMattina about the new NIH drug discovery center, and predictably he does not seem too happy about it. While the initial center was supposed to be all about translational research, the latest idea is to use the NIH's resources for "repurposing", or discovering new indications for old drugs.

LaMattina echoes some of the dissatisfaction that a few of us have earlier expressed about this idea. The main point here is that the NIH should not be in the business of discovering new drugs; it should be in the business of doing the basic biological research that may enable such potential discoveries. In fact one might argue that the biggest challenge facing drug discovery today is an incomplete understanding of the complexities of the biology underlying major diseases. Just think of the conflicting data and the complications that have emerged from attacking beta amyloid in Alzheimer's disease for instance. There's hardly any doubt that better treatments can only result from a proper evaluation of the basic biology of disease. And it's also clear that this understanding is not going to come from industry. Only the NIH and academic labs can accomplish this, and spending money on therapies when it could more fruitfully be spent on such fundamental studies seems to be folly. So ironically, funding drug discovery may hinder an understanding of the very foundations that may truly enable it.

Nor is what the NIH doing truly novel. As LaMattina points out, repurposing is an obvious route and an attractive one at that, since finding a novel indication for an old drug means that the drug has already run the gauntlet of FDA approval. So we can bet that industry would have worked on repurposing if they could possibly do it. Now granted, there's always going to be compounds that were dropped for financial or project-related reasons which may be potentially valuable agents for all kinds of conditions. And we can also assume that these numbers might have grown during the last few years when projects have been axed and personnel laid off in increasing numbers. But what are the chances that hidden among those dusty vials on the shelf is the next cure for pancreatic cancer? Of course one may never find out if one does not look, but the NIH's announcements make it sound like there's pure gold among those neglected compounds, waiting to be discovered. The fact is that examples of truly repurposed drugs are quite few; as LaMattina points out, even the two repurposed drugs cited by NIH director Francis Collins are drugs for which the "other" indications were rather obvious based on their mechanism of action. Repurposing by itself is not entirely misguided, but repurposing at the cost of basic biomedical research draws resources away from more worthy endeavors.

Thus, by and large LaMattina's arguments seem to be cogent. Unfortunately the indignation on the other side of the equation is not as justified as it sounds. LaMattina refers to a statement by legendary Merck ex-CEO Roy Vagelos along the lines that if there was real benefit to something that the NIH wants to do, pharma would already be doing it. Sadly this is increasingly not the case. In the last few years pharma has defined "benefit" based on whether something's going to affect the next quarter's profits. Working on Alzheimer's disease and other CNS disorders where the rewards are long-term but undoubtedly stellar is no longer considered a beneficial strategy. So we have a situation here where industry is rightly advising the NIH to work on basic research rather than drug development, but not committing itself to its part of the deal. As well-intended as it may be, the impact of your advice gets blunted a little if you stop looking in the mirror.