Zanubrutnib

[Fwanni]

Has anyone experience of zanubrutnib? It appears to have virtually no hair loss, with positive results.

[lankisterguy Volunteer]

Hi Fwanni,

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I have been watching the Zanubrutinib / Brukinsa space for some time, and some of our experts are predicting an approval shortly for CLL in the USA.

The few CLL patients that are using it here are obtaining it via an "off label" prescription from USA CLL expert doctors.

It seems that the only approvals in the UK are in England & Wales for Waldenstroms, uk.finance.yahoo.com/news/n...?

There are a few other approvals: brukinsa.com/ but I don't see any for CLL yet, and none are mentioned for NICE in Ireland.

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I'm curious about your comment on hair loss.

I had brittle nails and a skin rash for 9 months on Ibrutinib in 2015,

and now in 2022 I see that my hair is much thinner on Acalabrutinib / Calquence.

Is that the side effect you are concerned about?

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Len

[scryer99 in reply to lankisterguy]

cllsociety.org had an article up saying it has in fact been approved [EDIT: not by FDA yet though — see AussieNeil’s response below] and is now replacing ibrutinib for standard first-line new treatments in the US NCCN recommendations. Similar efficacy, lower side effects.

cllsociety.org/2022/11/nccn...

[lankisterguy Volunteer in reply to scryer99]

Hi scryer99

Can you find it on CLLSociety.org and post a link?

I searched and cannot find any mention of approval for CLL

cllsociety.org/?s=Zanubrutinib

or the pharma website: brukinsa.com/hcp/

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Len

[scryer99 in reply to lankisterguy]

Added in the link - definitely zanutrinib / Brunkinsa. What I'm not clear on is how NCCN recommendations dovetail with FDA approval chains. I figured they were lined up but maybe not.

[AussieNeil Administrator in reply to scryer99]

NCCN have approved zanubrutinib for CLL off label, simply because it has been approved for other, closely related blood cancers. FDA approval for CLL is said to be imminent.

Neil

[DebKat999 in reply to AussieNeil]

I recall reading that the "target date" for FDA approval was supposed to be October of this year. I wonder how soon it will actually be approved for CLL in the U.S.

Debbie

[lankisterguy Volunteer in reply to scryer99]

Brukinsa FDA Approval History

drugs.com/history/brukinsa....

Last updated by Judith Stewart, BPharm on Sep 16, 2021.

FDA Approved: Yes (First approved November 14, 2019)

Brand name: Brukinsa

Generic name: zanubrutinib

Dosage form: Capsules

Company: BeiGene, Ltd.

Treatment for: Mantle Cell Lymphoma; Waldenström’s Macroglobulinemia; Marginal Zone Lymphoma

Brukinsa (zanubrutinib) is a Bruton’s tyrosine kinase (BTK) inhibitor used for the treatment of mantle cell lymphoma (MCL), Waldenström’s macroglobulinemia (WM), and marginal zone lymphoma (MZL).

Brukinsa is indicated for the treatment of adult patients with:

Mantle cell lymphoma* (MCL) who have received at least one prior therapy.

Waldenström’s macroglobulinemia (WM).

Marginal zone lymphoma* (MZL) (relapsed or refractory) who have received at least one anti-CD20-based regimen.

Brukinsa capsules are administered orally at a dosage of 160 mg twice daily, or 320 mg once daily.

Brukinsa can cause serious adverse reactions including hemorrhage, infections, cytopenias, second primary malignancies including skin cancers, cardiac arrhythmias, and embryo-fetal toxicity.

Common adverse reactions include neutrophil count decreased, upper respiratory tract infection, platelet count decreased, rash, hemorrhage, musculoskeletal pain, hemoglobin decreased, bruising, diarrhea, pneumonia, and cough.

*This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Development timeline for Brukinsa

Date Article

Sep 15, 2021 Approval U.S. FDA Grants Brukinsa (zanubrutinib) Accelerated Approval in Relapsed or Refractory Marginal Zone Lymphoma

Sep 1, 2021 Approval U.S. FDA Grants Brukinsa (zanubrutinib) Approval in Waldenström’s Macroglobulinemia

Nov 14, 2019 Approval FDA Approves Brukinsa (zanubrutinib) for the Treatment of Mantle Cell Lymphoma

Aug 21, 2019 BeiGene Announces U.S. FDA Acceptance and Grant of Priority Review for its New Drug Application of Zanubrutinib in Patients with Relapsed/Refractory Mantle Cell Lymphoma

Dec 1, 2018 BeiGene Announces Clinical Results of Zanubrutinib in Mantle Cell Lymphoma From Two Presentations at the 60th American Society of Hematology Annual Meeting

[Fwanni in reply to lankisterguy]

Yes. Much thicker hair while ON Ibrut! Odd! But intense bone - wrists right hand fingers, neck turning driving and heels, brutal. Off Ibrut now nearly 5 months, all except heels, pain resolved. But front patches of hair loss happening Now, noticed by my surgeon..I wonder was it 3 weekly infusion changeover to Privigen? On Flebbogamma 5 for 3 years I found it brilliant but it was withdrawn! My reluctance 'to starting Acalabru is it is constantly reported as causing 'bad headaches'. I had an accident years back, had brutal continuous headaches over 4+ years. I don't want to start acalub and have to stop. I work so it is a balance act, tolerability...Bloods excellent.

I read up on zanubrutnib , very encouraging. I have to start one or other in the next couple of weeks now.

Zanubrutnib might be well worth following especially with Dr Peter Hillmen, Leeds University, V little downside reported?

Best...

F

[theclarksark]

I've been on Brukinsa for 10 months. I'm only taking half dose because I was initially very tired on a full dose and half dose is working perfectly -- all labs became normal. I initially tried Acalabrutinib but the hair loss was extreme. The hair loss seems to have stopped but I wouldn't say my hair has returned to it's healthy state yet. Joint pain has been an issue but I've managed that with Golden Paste Turmeric (which I make myself) 3 times a day. Hope your results are great also.

[MrMidnight]

I had nearly five years on a Zanubrutinib trial in Auckland, New Zealand (from Feb 2016-November 2020). I had very debilitating fatigue during my first year (I could barely walk to the letterbox and had to use a wheelchair to get down long hospital corridors) which slowly improved over the next 18 months as my blood counts normalised.

But the docs told me it was vey unusual to have such bad fatigue (I was the dunce of the clinical trial in that regard!).

No other side effects (and I'm bald so I have no idea how it might affect hair loss). I'm also 17p deleted so was very grateful for being on the trial.

[lizfuccillo]

I have been on zanubrutnib since 10/2021. Before that, I was on Imbruvica but had to stop due to several serious adverse reactions. Since starting zanubrutnib, the only adverse reactions I have experienced are high blood pressure ( for which I have been prescribed medicine) and bruising. No hair loss!! Most of the time the black & blue marks appear on my limbs however every once in awhile I get some on my torso and face.

[StBon]

Have been on zanubrutnib for 14 months. Very pleased with labs which are close to 'normal' and have been for 4 months. Fatigue - yes, but I am also approaching 80 with 10+ years of CLL behind me and I do volunteer work 18 hours a week. Hair loss - again due to med or age? And not extreme loss but very thinning. Fairly serious bruising on limbs, mostly just unsightly. Doc and I recently agreed to reduce dose from 360 to 280 a day to see if the good labs hold and the side effects reduce. Overall, I am very pleased with results. Best to you on your CLL adventure!

[Eliotf]

I have been on Zanabrutinib for 6 months and no issues. I also take a probiotic every day. As for the thin hair and brittle nail issue I do not know as I have another auto immune disorder that affects those two things as well as lots of other body parts

[AussieNeil Administrator]

With respect to hair loss, my reply to an earlier question on hair loss on ibrutinib is relevant: Does ibrutinib cause hair loss?

Ibrutinib, a Bruton Tyrosine Kinase (BTK) inhibitor, binds to the cysteine residue at the active site of Bruton's tyrosine kinase (BTK) and can change the disulfide bonds between cysteine residues. Whether this cancer mechanism may lead to the observed hair changes is not known.

drugs.com/medical-answers/i...

Given later generation BTKi drugs are more selective, you'd think that hair loss would be less likely, unless it is just a reflection of the increased health challenge your body is under during treatment. That the newer BTKi drugs are more selective, is indicated by the observation that you don't see the commonly mentioned changes in hair noted* for ibrutinib by members on other BTKi drugs.

*Most taking ibrutinib and commenting on hair changes mention their straight hair becoming wavy (or sometimes the converse), thinning and sometimes even thickening!

Neil