Duchenne muscular dystrophy (DMD) has always been considered a hard disease to come up with a treatment for. And how we have plenty of evidence to back up that belief: it’s catastrophically hard. Over the last few years, we’ve seen rival therapies go through all kinds of wrenching twists and turns. Prosensa was developing drisapersen, for example, and having a hard time of it, until they were bought by Biomarin for $680 million dollars. That investment seemed rather hopeful (I thought the drug was done for), but as pointed out here, it now looks to be completely wiped out. Biomarin tried to do what Prosensa couldn’t (convince regulatory authorities that the drug actually worked), but this effort has failed, and more than once. Drisapersen missed its primary endpoint in its big clinical trial, and Biomarin’s reanalysis of the data, about which they thought enough of to spend over half a billion dollars, convinced neither the FDA nor the European regulatory authorities. There’s nowhere left to go.
PTC Therapeutics was also working in Duchenne, but they didn’t even get their candidate (ataluren) thorough the front door for that indication. Update – it is approved in Europe, but not in the US, or at least not yet. (It’s under development now for cystic fibrosis). That leaves Sarepta and eteplirsen, which has recently been the subject of all kinds of widely covered FDA attention. The agency has delayed its decision, not that I blame them. This is one of those situations where a parade of parents and their critically ill children ask how you could possibly turn down the only drug that could help them – but at the same time, the evidence that the drug actually helps them is so thin as to be unusable.
In that last link, I presented four ways that the agency’s decision could be interpreted, and personally, I fall into the “should be turned down for lack of efficacy” camp. As it stands, we approve drugs in the US after showing safety and efficacy, and we balance those two in making a decision. If we decide to move to a system where we consider safety only, and approve things that have little to no evidence for any actual purpose, then we should be up front about that and change the mandate of the FDA to reflect that shift. Saying that “Oh, we’ll just let this one through” is the worst of both worlds. There are people who are willing to agree with this point but who also feel that eleplirsen has demonstrated enough efficacy to be approved, but I just don’t see how that argument holds up.
What would be so bad about moving to an “efficacy not required” regulatory regime? I think that it’s a flight from scientific evidence, which is the only thing we’ve got. Otherwise, everything starts to look like the “dietary supplement” industry, and what a mess that is. Here, you drop the efficacy requirement and I’ll develop grape juice for Dread Disease X. Not just plain grape juice – grape juice concentrate capsules. Mechanism? It’s the bioflavanoids. Probably. I think that they’re antioxidants, among other things. Lots of things. I can show safety in the clinic, too, so you have to approve my grape juice gel caps: I have a mechanism by which they might work (you can’t prove I’m wrong, can you?), I can show they’re safe, and you’ve eliminated the requirement that I prove that they actually do anything useful. Off to market! The patients who unfortunately suffer from Dread Disease X will, I’m sure, pay a lot for something that might help them. Don’t they have a right to try my antioxidants? There’s nothing else like them on the market, you know.
That’s the world that I worry about living in. And while it may be a reducio ad absurdum, I don’t think we need to reduce things very far to get to the absurdity. Unfortunately.