I wanted to note something today that won’t make many headlines outside of biopharma, but it’s just the sort of story that I wish more people knew about. Let’s start with this: there’s a terrible disease called IPF, idiopathic pulmonary fibrosis. Anyone with any medical background knows to beware the word “idiopathic”, since it’s a shorthand for “we don’t understand much of anything about this”. You’ll also know to beware the word “fibrosis”, for that matter, because it generally means a buildup of scar tissue that no one can do very much about. IPF happens in older patients, more males than females, and its features are progressive scarring of the lung tissue, driven by some ultimate cause that we haven’t quite been able to work out. The decline in lung function is progressive and irreversible, and most people who get the diagnosis are dead within a few years – short of a lung transplant, there’s really little to be done about the underlying problem. Pirfenidone and nintedanib are approved compounds for the disease, but in most cases they just slow down the inevitable a bit.
Now, this is part of a broader field of fibrosis diseases, affecting all sorts of organs and tissues (heart, lung, liver, kidney, etc.) Some of these we understand better than others, and we understand enough to know (simultaneously) that classifying so many things under “fibrosis” is an overreach, because such tissue effects are a symptom of something deeper (that “something” can be pretty wide-ranging), but also that the cell biology of fibrosis itself is often similar enough to make one hope for a relatively broad-based treatment of such symptoms. Which would definitely be an improvement over what we have now.
Back in 2012, Biogen bought a small company called Stromedix (founded in 2007) that had a candidate aimed at IPF. There’s a biotech-biz inside baseball angle to the story, because the founder of Stromedix was a former head of Biogen’s R&D (and has gone on to other ventures since), Stromedix came out of one of the well-known VC organizations here, Biogen had actualy developed the program initially, outlicensed it to Stromedix, and eventually came back around again, and so on. As with any technology hub, everybody either knows everybody or knows someone who knows them, and a lot of interesting stories get generated. But I’m leaving the human-interest and business angles aside, and focusing on the science and medicine.
The main compound involved, STX-100, is an antibody targeting the alpha-v-beta-6 integrin receptor. That’s upstream of TGF-beta, which has been shown to be a key player in fibrosis in general. (There’s one of those hopes for a general treatment). The integrin activates TGF-beta, so the hope was that targeting it would slow down or even halt the fibrosis process. Targeting TGF-beta directly is very likely a bad idea (it has just too many important functions), so there have been all sorts of attempts to bounce-shot the target by finding other targets that regulate its activity. The antibody had already been in trials for kidney fibrosis, but had shown some tox problems which apparently made it a better candidate for lung fibrosis – they’d gone into kidney patients first because there were easier to identify and monitor. And that’s where Biogen came back into the picture, buying the whole company and pushing the trials forward, because they’d looked at pulmonary fibrosis with it earlier and seen encouraging results.
STX-100 (now BG00011) went back into the clinic, with a trial ending in early 2017. But there wasn’t much news about that, although a Phase IIB went ahead in IPF patients last year. And (you probably knew where this was going), word has just come out that the study has been terminated with only about a third of its patients enrolled. That does look like the end of the line for this antibody, and it’s not particularly encouraging news for targeting alpha-v-beta-6 either (although there’s a small-molecule antagonist of it from GSK that’s
in the clinic now (edit: now terminated as well). And there are, fortunately, many other mechanisms being investigated by many other people, with quite a few trials going. Fibrosis is a major unsolved problem, and the first people who make real progress against it will do very well, and help a lot of people who have, frankly, very little hope other than something new appearing from R&D.
And that’s what I wanted to highlight: here’s a big cause of human suffering that not many people are aware of outside the medical field. The first time most people become aware of fibrosis as a disease is after they or someone they know is diagnosed, and that isn’t good news at all. There are, though, a great many people in academia and industry who have been working on this from many different angles for a long time now, but if you’re not a biomedical researcher you will never have heard about any of that work at all. I would also add that a tremendous amount of time, effort, and money has gone into all this, by the time you add it all up, and so far (from a can-you-help-me-doctor perspective), there’s been little to show for it. We’ve gained a lot of knowledge and experience, and (as this latest news shows) closed off some ideas previously thought promising, but there is no fibrosis cure to announce. Yet.
You will not see any big headlines about the demise of STX-100, either. Drugs fail all the time, most of the time rather quietly, and all the work and money that went into them just sort of vanishes. But that work, and that time, and that money – all of them were very real. As were the hopes of the people working on the drugs, and the hopes of the patients taking them in the clinical trials. This is happening constantly in the background, all the time, and it’s one of the big reasons that I started this blog in the first place, because almost no one realizes it.