Next Game Changer??

[EastBayDad]

There are a lot of very knowledgable people on this site who follow trials closely. Will the next CLL drug that will be a “game changer” be a BTK inhibitor that lasts longer, a more powerful version of Venetoclax that provides longer and deeper remissions, a combination of an existing drug and a new version of Venetoclax, or an entirely new class of CLL drug such as a degrader?

[flipperj]

I don't see any of the newer recycled versions of BTK and BCL2 inhibitors as becoming game changers in CLL. I would welcome another small molecule drug if it had a different target and efficacy in line with the BCL2 inhibitors, which are fantastic drugs IMO. This may be unlikely though as the industry is rapidly moving away from discovery of small molecule targeted drugs and into immune therapies. We are currently in somewhat of a transition period but I suspect in another 10 - 15 yrs the treatment landscape will be quite different and even these targeted therapies will have become a thing of the past.

[Skyshark]

Although still targeting the BTK path there are BTK degraders in development. Rather than binding to the BTK receptor to block the signal path these remove it.

cllsociety.org/2024/04/phas...

cllsociety.org/?s=BTK+Degrader

[thompsonellen2]

Having made it just two years on a combo BTKi and having just "failed" out of the BTK degrader in one week, I don't know that these new BTKi meds will be a game changer, at least for high risk people like me. I think the next big hope is epcoritimab which is a bi-specific T cell engager. Brian Kaufman blogs about it here cllsociety.org/treatment-an....

[dumbsaintmind]

I’ve been following data from the Zanubrutinib + Sonrotoclax trial which I believe is now in phase III.

Sonrotoclax is the next generation BCL2 drug that is reportedly 10x more powerful and selective. I imagine it will be used alongside obinatuzumab or some BTKi.

It will be nice to have another BCL2 in addition to Venetoclax. I imagine it could lead to deeper remissions.

[Smakwater]

EastBayDad,

What do you mean by game changer, cure?, less toxicity?, more affordable?

In my view they are all game changers in that everyone responds differently and every new addition is a step closer to the last best option. Whereas some are resistant to one drug, another has a complete and durable response that has an outcome for quality of life being nearly equal to a cure. Many who have cll are living beyond the average life span and with better quality of life than some without the disease. Every time that there is a new offering even it is a single offer, it is exponential in that it can be considered for combination use in double, triple, quadruple, even multi such as RCHOP.

When I began my cll journey, FCR was the only approved drug available and offered a poor prognosis. At the time that I was diagnosed, a friend of mine relapsed, developed Richter's, and passed four months later. I cannot help but think that he may have been able to avoid Richter's and still be enjoying life if he had any option of the drugs that came available only one year later. That was nine years ago and although there is yet no cure and there are still side affects, The contrast from that day to now is immeasurable from my perspective.

As far as efficacy, durability, toxicity... , the game is changing so fast as we speak that the research cannot keep up. If you mean cure when you say game changer, then what will happen is that the C in CLL will mean Curable rather than Chronic(Curable Lymphocytic Leukemia). I do like the sound of that!

If we take a close look that what is on the horizon, the next step might be viewed as a sprintathon. Research is having difficulty deciding which direction to go because there has been so much new data available. Even so that there is a trial participant shortfall inhibiting the advancement of discovery. If it were not for the reduction in the research dynamic caused by covid, we may have found the optimum drug by now.

For me, the greatest game changer at this time would be to minimize the financial toxicity and the side affects of anxiety and despair caused by not being able to pay for the novel drugs we have now.

You raise a good question. Lets all push until the C is redefined.

Be Well EastBayDad.

JM

[EastBayDad]

Reading For Blood and Money showed me that the combination of finance and science will never lead to cheaper drugs. Newest T-Cell therapy is $1.2 million. 😢

My doctor in Bay Area is involved in two degrader studies. I am heading to NIH in DC in three weeks for testing. I will ask them the same question I asked you and report back.

[AussieNeil Administrator in reply to EastBayDad]

The profitability of ibrutinib and the wider promise of BTKi therapy, led to a total of sixteen BTKi drugs either approved for CLL or in clinical trials for CLL. healthunlocked.com/cllsuppo... approved BTKi drugs following ibrutinib have lower side effect and adverse event profiles, such that people on these newer BTKi drugs are significantly less likely to quit due to intolerable side effects, which means longer progression free survival.

We also have several BCL-2 drugs in clinical trials for CLL. BeiGene, the manufacturer of zanubrutinib and sonrotoclax (a BCL-2 inhibitor), pitched the market price of zanubrutinib lower than that of ibrutinib to increase their market share.

Neil