A Conversation with Dr Tam about Zanubrutinib: A Novel BTK Inhibitor

[Jm954]

How does zanubrutinib differ from ibrutinib in pharmacokinetics and target occupancy?

Zanubrutinib has a more-specific target binding profile than ibrutinib. It binds to BTK at least as potently as ibrutinib. Zanubrutinib has fewer off-target effects on related enzymes, including the epidermal growth factor receptor (EGFR), interleukin 2–inducible T-cell kinase (ITK), Janus kinase 3 (JAK3), human epidermal growth factor receptor 2 (HER2), and tyrosine kinase expressed in hematopoietic carcinoma (TEC).

There is the potential that zanubrutinib can hit BTK with fewer off-target side effects. For example, it is thought that the rash and diarrhea sometimes seen with ibrutinib may be related to EGFR blockade. Ibrutinib may not combine well with monoclonal antibodies, such as rituximab (Rituxan, Genentech/Biogen), because of ITK effects on the immune effector cells. Zanubrutinib has the potential to target BTK with fewer off-target side effects, and it may combine better with monoclonal antibodies.

More here: hematologyandoncology.net/a...

Jackie

[BluMts]

Thanks Jackie. I've had and still get IB side effects. These other drugs are of interest. Do you have more info on Aclabrutinib? Though until these treatments are approved in the UK, it's pointless for us to get excited. I was told medically over a year ago that approval for Aclabrutinib was expected soon in UK.. FDA had already given their approval and I know there are trials in the US and France and I guess other countries. Are there any trials in UK and if not what's going on.. Do you know? I'm not enquiring about NHS funding which is a separate issue.

[Murzik in reply to BluMts]

Acalabrutinib is not approved by FDA for CLL yet, but got accelerated route for approval.

I am also very interested how better/ less side effects with at least the same efficacy/ Zanubrutinib will be compared to Acalabrutinib. Be well, G.

[Jm954 Administrator in reply to BluMts]

NICE are planning to look at Acalbrutininb, at the moment they are saying early next year. Fingers crossed as I am in the same situation as you - not enjoying the dreadful cramps that are not diminishing at all.

Jackie

[BluMts in reply to Jm954]

Thanks Jackie.

[Wroxham]

Thanks Jackie.

Sue

[WarriorPrincess4]

I've been on Zanubrutinib since November 2018 and have responded very well to it. I've had very little side affects. The only thing I notice is that I'm much more susceptible to colds and viruses. This is caused by my CLL and not the Zanubrutinib. This past summer I had Shingles which really scared me! I immediately thought of Lola and thought that my life too would end sooner than expected! Thank God this did not happen. I was given Valaciclovir and this helped. I now take it twice a day as prevention . A few weeks ago I developed something else which almost looks like Shingles but I am awaiting a referral to a dermatologist for a scraping to find out what it is exactly . In the mean time my Hematologist upped my Valaciclovir. The bumps started on my foot and developed into horrible looking blisters 😱 really ugly! My foot was bright red and looked as if it was scalded!

As these things often go I was on vacation when the blisters started expanding. Enfin I'm back home now and thanks to the extra Valaciclovir the wounds on my foot are healing and the new bumps developing on my leg seem to be calming down too.

CLL SUCKS!! Boohoo! Just when I thought I had everything under control and I almost forgot that I have this cancer I get reminded (on vacation) that I am not as 'healthy' as I feel or think. Then again, I'm always the optimist, things could be a lot worse! So I count my blessings and smile once again. My foot and leg and the blisters (probably due to a herpes virus) that even made it's way to my face (🙁) will heal! 😊

All in all I am fortunate to be on Zanubrutinib. 🐈🌷 Ellen

[Jm954 Administrator]

Ellen, you must be one of only a few people on Zanubrutinib, France is leading the way! I'm glad to hear that it's working so well for you with little side effects apart from the skin issues. Hopefully those will be sorted soon and you CAN forget about CLL and live your best life for a long time to come.

Jackie

[WarriorPrincess4 in reply to Jm954]

Thanks Jakie! I am certainly going to give it my very best shot! 😄 Life is beautiful even with CLL.

Ellen

[Yarwis]

I'm on a trial in the UK : Ibrutinib v Zanubrutinib. I got the Zanubrutinib arm. Started in July 2019. So far I've had a lot of spontaneous bruising but little else. My last ECG was abnormal but associated bloods were fine. Not sure what, if anything, is going on. Awaiting an ECHO for more clarity but I have no symptoms so am feeling positive.

[WarriorPrincess4 in reply to Yarwis]

Hi Yarwis! Pleased to meet an other fellow Zanubrtunib user! I had a bit of bruising too in the very beginning but that disappeared quickly once my body got used to Zanubrutinib. All the best to you.

Ellen

[Yarwis in reply to WarriorPrincess4]

Thanks Ellen, it's good for me to know of someone else on Zanubrutinib, too. Glad you are doing okay with it.

Shingles is a pretty horrid thing to get - I had it after my STC many years ago. Hope it's coming under control. I'm hoping it doesn't come back. I'm on a prophylactic dose of acyclovir just in case.

I've had CLL a long time (25+years) and I love life and the things it has taught me. This is another challenge to face but I love that treatments are improving all the time.

Keep smiling

Val xx

[otonal]

My neighbour is on a Zanubrutinib trial at UCLH Macmillan UK.

[Smakwater]

Zanubrutinib is looking good for the Waldentrom's, Follicular, MZL and even DLBCL group. Very encouraging.

JM