ASH 2025 | Bexobrutideg in CLL and approaching the sequencing of BTK degraders and inhibitors

Thanks for the question about the degraders. And the first thing to comment is the new names. We figured it out that it will be best to call it after the compound, which in this case was Bexo. Then the second part of the name is bruti and relates to the enzyme which is degraded and -deg is of a clear distinction from inhibitors. So bexobrutideg, it’s one of the degraders we have a very good practice with. It occurred to be effective and relatively well tolerated in a patient failing previous BTK inhibitors, including non-covalent BTK inhibitors. The study is in a variety of indications. But, so it happens nowadays, it reminds me, the BRUIN study with pirtobrutinib, which we in Europe called an American phase one/two study on steroids. We included over 800 people there with expansion groups. But bexobrutideg is something which we cross our fingers and we look very much forward. 

At the end of the day, I think that the idea of constantly blocking BTK pathways by first and second and third generation inhibitor is a rotten idea because sooner or later we will develop the resistance what should be done we should possibly block the pathway once maximum twice so it’s very likely that we will use our favorite BTK inhibitor followed by BTK degrader. Now what’s the favorite inhibitor will depend from the person you ask. With ibrutinib losing the patent rights, it’s fairly likely that its price will go down. So I wouldn’t call ibrutinib the dead drug. Now some of us will go for the second generation inhibitors which are selective and relatively non-toxic. My favorite is pirtobrutinib, but as I said, answers to these questions will vary depending on who you ask.

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