Treatment-naive or relapsed CLL patients will soon have zanubrutinib/Brukinsa as a treatment option in the EU

[AussieNeil]

The EC approval is based on positive results from two Phase 3 clinical trials: SEQUOIA (NCT03336333), in patients with previously untreated CLL, and ALPINE (NCT03734016), in patients with R/R CLL. In these two trials, BRUKINSA demonstrated superior efficacy versus either bendamustine plus rituximab (B+R) or ibrutinib in first-line or R/R CLL, respectively. BRUKINSA is the only BTKi to achieve superiority versus ibrutinib in R/R CLL, as assessed by independent review committee, with an overall response rate (ORR) of 80.4% vs 72.9% (p=0.0264).i Additionally, more BRUKINSA patients than ibrutinib patients had a sustained response at 1 year with rates of 90% vs 78%.i The adverse events within the two trials were consistent with the overall safety profile of BRUKINSA. Subsequent to the regulatory submission, BeiGene announced topline results of the final PFS analysis of the head-to-head ALPINE trial, in which BRUKINSA demonstrated superior PFS compared with ibrutinib in patients with R/R CLL.

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businesswire.com/news/home/...

[CycleWonder]

How does Brukinsa compare with Pirtobrutinib? Is it also taken in pills or tablets? What about side effects?

Good to know there’s a new option for treatment.

[AussieNeil Partner Administrator in reply to CycleWonder]

Per drugs.com/brukinsa.html

Usual Adult Dose for Lymphoma: (for Brukinsa/pirtobrutinib)

160 mg orally 2 times a day until disease progression or unacceptable toxicity

OR

320 mg orally once a day until disease progression or unacceptable toxicity

Side effects are listed further down the drugs.com page for Brukinsa/zanubrutinib

What can you tell us about how you take pirtobrutinib in your post? Drugs.com doesn't yet have a page for pirtobrutinib but the pubchem site has an exhaustive amount of information, including what appears to be a comprehensive list of clinical trials: pubchem.ncbi.nlm.nih.gov/co...

The two drugs primarily aren't directly competitive, but complementary in my opinion, so we may never have a head to head comparison of Brukinsa/zanubrutinib and Pirtobrutinib unless one of the manufacturers sees a competitive advantage, as was seen with acalabrutinib and ibrutinib. That's because they bond differently to the BTK 481 cysteine residue, per The most common resistance mechanism in patients whose disease progresses on covalent BTK inhibitors (BTKi) is a mutation in the BTK 481 cysteine residue

sciencedirect.com/science/a...

The two BTK inhibitors zanubrutinib and pirtobrutinib bind covalently and non-covalently respectively. Per the above reference, when you develop resistance to a covalent bonding BTKi, you are likely to be able to continue on BTKi therapy by switching to a non-covalent BTKi drug. Presumably the reverse is true.

Neil

[CycleWonder in reply to AussieNeil]

I take two 100 mg tablets once a day (total one time dose of 200 mg). The pills are normal size - not huge and not small.

[AussieNeil Partner Administrator in reply to CycleWonder]

Nice! They should be fairly easy to take and more importantly, if anyone taking it has side effects, they have the easy option of halving their dose without reducing their coverage throughout the day. That option isn't currently possible with acalabrutinib, where you take one 100mg capsule (now tablet) twice a day, as there's no 50mg dose. It might also be a limitation of some of the other BTKi drugs in clinical trials for CLL.

[Catnap7]

Good to know Thanks!

[RobertCLL]

Would Brukinsa still not be recommended for those that have relapsed on Ibrutinib?

[AussieNeil Partner Administrator in reply to RobertCLL]

That's right. Both Brukinsa and Ibrutinib bond covalently, so resistance developing in either would be for both. You'd need to switch to one of the new, non-covalently bonding BTKi drugs, none of which have been FDA approved, though pirtobrutinib is close. Unfortunately this means a wait before a non-covalent bonding drug will be generally available, particularly in the UK . At least we are looking a median time of 5 years before resistance develops on the approved, covalent bonding BTKisl, with some ibrutinib trial participants entering their second decade of maintenance management now.

Neil

[RobertCLL]

Thank you. I have been on Ibruitnib for nearly 6 years. I believe Venetoclax would be my next treatment (dependent upon other drugs becoming available).

[spi3]

Thank you for sharing yet an other exciting treatment in the potential cure for CLL Warriors

[GRMat158]

Excellent news - I've been taking Zanubrutinib on the Alpine study for just over three years without any significant side effects.

[Heeler0507]

Thanks Neil. This is promising. I recently missed out on a Clinical Trial of Zanibrutinib/Venetoclax combination in Australia because I was diagnosed with Melanoma 3 weeks before starting the trial which was a real blow. I will be starting O&V treatment in January but hope that after this treatment and whatever remission I am able to achieve, Zanibrutinib may be available in Australia on the PBS by then.

[AussieNeil Partner Administrator in reply to Heeler0507]

I'm sure the competitive zanubrutinib pricing will be attractive, plus we Aussies would gain access to what looks to be a very good BTKi.

How disappointing for you to miss out on the Zanibrutinib/Venetoclax combination. Still O&V is a very good treatment. Just be aware that you won't be able to produce antibodies for at least a year after your last obinutuzumab infusion, from infections or vaccinations, though you should still have T cell responses. The immunophenotyping blood test will report whether you have any B cells.

Neil

[Heeler0507 in reply to AussieNeil]

Thanks Neil. I've had 5 Covid vaccines during W&W, due to have 2nd Evusheld this month and have had 2 Shingrix Vaccines and the Prevnar13 vaccination so I'm hoping those are all working, or at least doing something, in my body before treatment starts.

[CLLerinOz Administrator]

Late Breaking Abstract for ASH 2022: "As ALPINE is the first study to demonstrate PFS superiority in a head-to-head comparison of BTK inhibitors, zanubrutinib has now proven superiority to ibrutinib in both ORR and PFS in pts with R/R CLL/SLL."

healthunlocked.com/cllsuppo...

[nuji]

For those who don’t have insurance or for those who want to self-pay for Zanubrutinib treatment with instead of Ibrutinib or Acalabrutinib, what would be the annual cost of treatment with Zanubrutinib in UK or Europe?

[AussieNeil Partner Administrator in reply to nuji]

BeiGene are trying to carve out a market with cheaper prices, but they aren't exactly a bargain at US$13, 000 to 15,000 per month!

[nuji in reply to AussieNeil]

Ouch! 😞 This means for people without insurance and means and for those without a good NHS, people just have to wither away 😢

Wonder if Hippocratic Oath that doctors take was the root for the word hypocrite?? 😞

[AussieNeil Partner Administrator in reply to nuji]

To be fair, doctors don't usually develop and prescribe the drugs. We do thankfully have separation of treating specialist and treatment supplier, which is a much bigger issue with alternative treatments. CLL specialists in the last 4 years, have put a huge amount of research work into exploring various combination options to come up with a few fairly good fixed term therapies which may or may not include a BTKi drug, such as zanubrutinib. That wouldn't be happening if pharmaceutical companies had their way, as they'd definitely prefer a maintenance treatment for life!

It's disappointing that we haven't seen more competitive pricing for BTKi drugs, given we have about 15 in play, but keep in mind that B cell cancers are fairly rare, so there isn't much of a market. Vendors have understandably decided to differentiate their offerings on factors other than price.

Neil