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IDO Inhibitors Hit A Wall

Apr. 09, 2018 1:46 PM ETIBB, INCY, MRK, BMY2 Comments
Derek Lowe profile picture
Derek Lowe

Friday brought some very unwelcome news in oncology. I've written about IDO inhibitors before, partly in the context of an odd situation between Incyte (INCY) and Flexus, and partly in response to a recent failed trial of a compound from NewLink. That last one shook people up a bit, but (as I mentioned in the post) there was still hope for combination of the Incyte drug with Merck's (MRK) Keytruda (pembrolizumab). The idea is that IDO inhibition would increase T-cell activity and add to Keytruda's effects.

Unfortunately, that is not the case. The companies have announced that the Phase III trial of this combination in melanoma has utterly missed its endpoints, and that appears to be a massive setback for the whole idea. Add that to the earlier difficulties with other IDO compounds, and the picture is Not Good. Bristol-Myers Squibb (BMY) has a big trial going with their own Opdivo (nivolumab) and their own IDO1 inhibitor (BMS-986205) in melanoma, and this bodes very ill for those results indeed. It has to be noted that they've announced what appear to be positive results for that combination in other trials, but hey: Merck and Incyte had what appeared to be decent-looking results early on, too. The feeling when this trial was announced was that since the company was not waiting for the Merck readout that they must have been pretty confident. But that could also reflect the company's feeling - not unjustified at all - that they're locked in a brutal struggle with Merck in this area and had no time to sit around.

This is not only bad news for melanoma patients, for Merck, and (especially) for Incyte. And it's not only potentially bad news for BMS. It's potentially bad news for everyone who thought that their understanding of these pathways was good enough to predict

This article was written by

Derek Lowe profile picture
Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek, email him directly: derekb.lowe@gmail.com (mailto:derekb.lowe@gmail.com)

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