I wrote a couple of months ago about the disappointing results that AbbVie had obtained with their cancer stem cell therapy “Rova-T” (rovalpituzumab tesirine) in small-cell lung cancer. This was the antibody-drug conjugate that they’d purchased from Stemcentryx – OK, let’s clarify that, they bought Stemcentryx out completely for nearly six billion dollars, largely to get their hands on this great new drug. As that March post says, though, the clinical results were deeply unimpressive. AbbVie stock took quite a hit on the news, even though there were already grounds for suspicion about just how the trial (TRINITY) would come out.
Now the company has done a more thorough presentation of the data at the American Society for Clinical Oncology (ASCO) meeting, and if anything, it’s even worse than it appeared in March. @zbiotech on Twitter is quoting a Leerink analysis (by Geoffrey Porges, I assume, who has been following this drug’s progress closely), and it’s not the tiniest bit encouraging. “The results shown in the presentation were even worse than we had feared. . .we can’t help but regard the ongoing trials as largely fruitless exercises“. That sort of thing.
Another problem for AbbVie is that it’s the adverse events that are sinking Rova-T, and those may be built into the other programs that they bought from Stemcentryx, since these apparently use the same cytotoxic payload. At the very least, it casts a real shadow over things. Going back and reading that last link, the 2016 press release announcing the deal, is a grim experience. It’s all about how this is a multibillion dollar opportunity, expected commercialization in 2018, compelling data in the earlier trials, etc.
But let’s go back to that Leerink analysis: “The TRINITY study provided yet another lesson in the perils of relying on single arm early trials without doing a randomized trial. . .” It certainly does that. Not everyone would have reached into their pocket for $5.8 billion on seeing the earlier Stemcentryx data (that figure on AbbVie), but you could have gotten a lot of people to agree that it looked promising. But “promising” or even “compelling” clinical data are only as solid as the clinical trials that generate them, and single-arm trials are just not solid enough to put that kind of money down on them with any real confidence. Sure, you’re going to win sometimes – but don’t pretend that you’re not gambling. And don’t get the idea that I’m speaking out against taking those kinds of risks in this business (sometimes you have to), but it would help to be a bit more honest about them.
It’s also worth thinking about this situation in light of that <sarcasm> amazing, life-saving Right to Try bill </sarcasm> that was just signed. This is exactly the sort of drug that comes under its purview. Early, early stage results, promising for a deadly disease. Give it to the poor desperate patients! But that’s no kindness: Rova-T turns out to be worse than the standard of care. You are not only not helping lung cancer patients with it, you are objectively doing them harm.
And this is what happens with the involvement of a huge, perfectly competent drug company that is willing to spend billions of dollars up front. What happens with smaller, shakier even-less-statistically powered approaches to deadly disease? Well, what do you think? And that doesn’t even take us to the bigger fear I have about the whole approach, that even worse outfits will configure themselves just to make money off the desperately ill, in completely legal fashion, without even bothering themselves about whether the
marks customers patients have any chance of being helped or not. We’re not there yet, but we’ve opened the door to it. Haven’t we, Senator Johnson? There’s a man who apparently has no opinion whatsoever about the ability of the President to pardon himself – Hands in the air! Huge shrug! Who knows! – but he is confident that the FDA needs to get out of the way so that people can take drugs like Rova-T. Here we are.