Readers may recall a post here last year about an odd trial of an antisense drug for Crohn’s disease. Celgene had acquired the drug (mongersen, GED-301) from Nogra Pharma of Ireland back in 2014 as a late-stage candidate, and for a while, things looked good. In fact, going back and reading the stories, you’d think that everything was pretty much on track:
Celgene ($CELG) bet big on the little-known Irish biotech Nogra Pharma when it partnered on a mid-stage drug for Crohn’s disease. And today Celgene spelled out the reasons why it gambled $710 million upfront on a Phase II drug, highlighting data that support a clear case that the therapy can help spur clinical remission in a broad group of patients.
An oral antisense agent is a pretty bold move, but then again, a Crohn’s drug of that sort just needs to hit its target in the gut wall, not make it into circulation. And mongersen’s target is Smad7, a key player in the transcriptional signaling machinery for an important inflammation pathway (among other things). This is the sort of target that is very difficult indeed to go after with a small molecule, and that’s when you see the antibodies and oligonucleotide-based modes get tried.
Later results were not as encouraging, though. And the reason I called that trial uninterpretable almost exactly a year ago was that it had no control arm, making it very hard to tell the difference between mongersen’s effects and a placebo. On Friday, Celgene had an announcement on a full placebo-controlled Phase III trial, and guess what? It actually isn’t that different from a placebo. Fancy that. The announcement was that the trial was being discontinued due to futility; an interim analysis showed that nothing was happening.
Unfortunately, that candidate was actually a pretty important part of Celgene’s plans and revenue projections. When the company did their 2014 deal, it raised eyebrows because of the steep upfront price for a relatively unproven therapy from a relatively unknown (and very small) partner, but Celgene was (as they said at the time) into Planning Boldly For the Future, as well as Executing Transformative Deals on Late-Stage Clinical Assets and all that stuff. Unfortunately, the science crept up and sank its teeth into the ankle of this mighty deal, and one would assume that mongersen itself is no more. There’s a lot of finger-pointing about putting that much money into something so thin, but of course if the compound had worked, everyone would be taking visionary dealmaker victory laps. It’s evaluating that “if the compound works” part that is the tricky part, and a tiny company’s oral antisense agent for Crohn’s was always going to be a gamble. You just wonder if it had to be quite as expensive a gamble as it was.
And as always, whenever something like this happens, I will remind people that this is why you run big, well-controlled Phase III trials. Back in Phase II, mongersen looked as if it were going to work (as that quote above illustrates). It doesn’t seem to have any particularly bad safety issues, so under some regulatory proposals, that would have been the time to let suffering Crohn’s patients take it on a risk basis, speed up development, get the regulatory barriers out of the way, all that stuff. But that would have given everyone three years of useless placebo, at a no doubt stiff price. And since more drugs in clinical trials fail than work, I’m still baffled at how giving people a chance to pay for them at that point is supposed to improve health or save anyone money. It certainly wouldn’t have in this case. Celgene stuffed well over $700 million in real money into the shredder on this effort, and a million Crohn’s patients could have joined them.