You may be familiar with the bizarre story of TGN1412, an immunotherapy developed (briefly) by a small German company called TeGenero in 2006. This led to the infamous Phase I incident in England where a set of six volunteers were dosed at fifteen-minute intervals, but right after the last one got the injection, the first one collapsed. And then the second, and then the third. . .it was a long morning at the office, that’s for sure. Everyone involved ended up in intensive care for some time, and although none of the six died, it was clearly a very near thing.
This incident pretty much rang down the curtain on TeGenero and on TGN1412, as well it might. I remember thinking at the time that we’d never hear about it again, except as a vivid case of How Not to Do It. But an alert reader spotting this in the British Medical Journal, from back in April: TGN1412 is about to go back into humans as a potential arthritis therapy. I never would have believed it. Here’s a story from Reuters to the same effect.
The key seems to be better in vitro tests to predict such “cytokine storm” reactions. The compound is now being dosed at about 20x less than the TeGenero incident, and throttling back to about 5% seems to bring things back into a zone of safety, while still providing immune effects. (Keep in mind that even the original TeGenero dose was calculated to be far below a therapeutic one, based on what was known at the time – it’s a good thing that they didn’t try anything higher, or no one would have made it as far as the back of the ambulance). This time, Phase I trials appear to have been successful, and Phase II enrollment is going on for what’s now been renamed TAB08 (from TheraMab, the Russian/German firm that bought the rights from the bankrupt TeGenero).
If this works, it’s going to be an extraordinary story, and a real triumph of pharmacology (from what was a disaster of clinical research). An active compound – and boy, this one certainly is that – can, with enough work behind it, find a way.