Great News on MSNBC : msn.com/en-my/health/other... - CLL Support
Great News on MSNBC
Here is the story without the adverts:
Joe was 'at death's door' - until pill beat his cancer in six months
Patients battling incurable leukaemia blood cancer have been thrown a lifeline – thanks to an experimental pill that's been described as 'like something out of a sci-fi movie'.
In an early trial of the drug – which is known as NX-5948, and is so new it doesn't have a name – a 59-year-old patient who had run out of treatment options and had only months to live, has seen his cancer all but disappear after he began taking the pills.
Joe Murphy, from Hulme, Greater Manchester, is only the second patient in the world to be offered the treatment at The Christie NHS Foundation Trust, and he says it brought him 'back from the brink'.
The former bar manager was diagnosed with an aggressive form of chronic lymphocytic leukaemia (CLL) in 2015, which had recently spread to his spinal fluid and brain.
The disease, which causes abnormal white blood cells to build up in the blood and bone marrow, can at first be controlled using tablets, which allow patients to live for nearly a decade more after diagnosis.
However, over time, the cancer cells become resistant to treatments. This means that, for patients diagnosed at a younger age, there is a desperate need for more medicines. CLL kills more than 1,000 people in the UK every year.
Last year, Joe stopped responding to the third drug he'd been on to control his cancer. He lost more than a quarter of his bodyweight and, as his immune system weakened, had been hospitalised with sepsis and meningitis.
But today, thanks to the fact he was offered the pioneering drug, tests show almost no evidence of disease. 'I wouldn't be here today if it weren't for the trial,' Joe said. 'After the third treatment failed, I was preparing to die. I was not in a good place.
'But this drug has kept me alive and well since June last year. It's incredible – like something out of a sci-fi movie.
'I'm putting weight back on, my blood count is fine, my lymph nodes have shrunk back to near normal, and it's worked successfully in getting rid of the cancer in my brain, which is such a relief.'
While doctors don't know how long it might keep the disease at bay, Joe says he is now 'hopeful' and can look forward to celebrating his 60th birthday in December.
CLL, which affects more than 4,500 Britons every year, is the most common adult blood cancer and makes up 38 per cent of all leukaemia cases.
Around 40 per cent are aged 75 and older. People with a family history of CLL are more likely to get the disease.
It is more common among men, for reasons that scientists still do not understand.
Standard treatment for CLL include inhibitors, which block signals that make cancer cells grow, immunotherapy, which works by binding to and killing cancerous cells, and chemotherapy.
Patients may also be offered combinations of these treatments, which studies show gives better results. NX-5948, developed by San Francisco-based drug firm Nurix Therapeutics, is in a new class of treatments for blood cancers known as degraders.
They work by taking advantage of the natural disposal system inside cells – in this case, targeting a specific protein that CLL cancers need to grow and 'tagging' it to be destroyed.
Dr Emma Searle, consultant haematologist at The Christie, who was principal investigator for the trial, said: 'This might be the breakthrough we've been looking for in the treatment of CLL.
'The drug targets a pathway that CLL cells are particularly dependent on and basically blows it up.
'As doctors, we're excited because we're seeing a response, even at a low dose, in patients who've exhausted all of the standard care options and are very difficult to treat.
'To already see some of our patients like Joe responding so well to the treatment, with minimal side-effects, is very promising.
'Only time will tell whether this makes it to market, but it's about as promising as an early-phase study gets.'
The U.S. regulator, the Food and Drug Administration (FDA), has already granted the treatment fast-track designation – which means patients may get access to it more quickly – because the early results are so promising.
Further phases of the trial are ongoing.
Wow, great news, thanks for sharing, nice to have good news on a Monday morning
Hi Mick,Pleased to tear your positive news, I also have been on same trial drug since early February at Oxford and so far all seems fine.I have completed 2 cycles and just started third. No side effects to date, good luck.
Hi Mick,Pleased to tear your positive news, I also have been on same trial drug since early February at Oxford and so far all seems fine.I have completed 2 cycles and just started third. No side effects to date, good luck.
and here is a link to a similar story from the BBC about this trial drug:
Seems to be a very promising drug. Thanks to all those amazing scientists and doctors who continue looking into new pathways to destroy the CLL cells.
Thanks to East Bay Dad and Mick for the ‘translation’. Seems very good news
I'm sure it sounds exciting. However, there's a long way to go before verifying whether this is an oasis or a mirage.
One would do well to monitor following progress through more scientific releases hopefully, and manage their expectations accordingly.
Media is great at getting a story out; it's their business. A phase one trial is more at the 'proof of concept' end of the spectrum than the 'dialing it in' outcome.
sciencedirect.com/science/a...
This article discusses the science They have been looking at degraders for 20 yrs now It does have a ways to go but it sounds very promising.
Whats more encouraging is that is big pharma companies are teaming up with smaller bio companies in a race to get these drugs to market.
This is actually great news for us. For many of us with cll, if we become resistant to a btk inhibitor drug like ibrutinib and to a bcl-2 drug like venetoclax, our options are limited.
They have made progress with new btk inhibitor drugs that bind differently than the original btk drugs and overcome resistance. But so far it appears that the non covalent drugs might not buy us a lot of time.
What we need is a completely new class of drugs and thats what nx-5948 is. It can be confusing because nx-5948 targets btk, the same enzyme ibrutinib, acalabrutinib and pirtobrutinib do. But nx-5948 targets btk in an entirely different way than ibrutinib type drugs and can overcome resistance to them.
Ibrutinib, acalabrutinib, zanubrutinib and pirtobrutininb are all inhibitors. They inhibit btk, an enzyme that cll cells have too much of that makes the cll cells live too long. Many people who take btk inhibitors will eventually become resistant to them due to btk mutations.
Nx-5948 is a degrader drug that works differently than inhibitors and can overcome resistance. Nx-5948 degrades btk as opposed to inhibiting it. Its imperative we have not only new drugs, but different classes of drugs, as it appears to be the nature of cll to eventually work its way around whatever drugs we take for it.
Further good news is that small bio companies have been looking to hit it big with degrader drugs for all sorts of cancers and that some of the big pharma companies have taken notice and are investing in the research and partnering with the small start-up companies researching degraders. The first to market could make billions, so it’s an arms race of sorts among pharma companies, which is great for us.
I have no idea how far away we are from approval and if problems will arise, but it’s great news to see that there is increasing access to these drugs through clinical trials. People resistant to traditional btk and bcl-2 drugs need options to car T and stem cell transplants, and sooner than later.
Here are a few articles on the degrader technology for those interested. It’s a lot of science mumbo-jumbo, but I get the gist I think. Gardening Girl or Neil I am sure could explain this better.
biopharmadive.com/news/aste...
sciencedirect.com/science/a...
en.wikipedia.org/wiki/Prote...
Thank you Jeff. Without getting into the weeds on the biochemistry, you've given an easy-to-understand explanation. I really appreciate it.
The BTK degrader trial my specialist is doing, is from a different company. "Arms race" hahaha!
ashpublications.org/blood/a...
Yes, “arms race” might be a stretch of an analogy. :). But we use these drugs as weapons of sort to kill cancer cells. And the company that gets the best drugs to the market first, reaps the benefits.
The different company in the article you have linked to is Abbvie, and I think thats even more good news for us. Abbvie has partnered with other companies to bring ibrutinib and venetoclax to the market, so one might argue that Abbvie is the premier pharma company for developing drugs to treat cll.
The fact that a company like Abbvie is developing degrader drugs is good news not only because Abbvie must have faith that degrader drugs can get to market, but also because Abbvie has enormous resources to accelerate that process.
And the fact that the motivation to beat the other companies to market is probably more profit driven than saving lives like ours, bothers me none, whatever gets me access faster is great no matter the motive. It’s critical to almost all of us treating with novel agents for our cll that we have options after btk and bcl-2 inhibitors and before carT and transplants. Degrader drugs sound a real possibility. Bispecific drugs and vaccine therapies might help one day.
Better performing generation drugs from the same class are great, but usually resistance to one is resistance to all, but for maybe a non covalent btk inhibitor that’s kind of a different. I was excited to read about the encouraging early success with degrader drugs, because that’s a whole new class of drugs with a different mechanism of action. I am assuming (or hoping) that degrader drugs for cll wont be limited to btk targets. There could be a lot of other proteins to target, but that’s over my head. Hopefully Gardening Girl will weigh in on dergaders and what the real potential is for us with this new class of drugs.
All your points were great Jeff, always glad to have an extra hope, like I said, just managing expectations.
I think "arms race" is a great analogy and I'm especially happy about the "race" part. 😉
"Nx-5948 is a degrader drug that works differently than inhibitors and can overcome resistance".
I'm pretty sure I read that BTK degraders can even reset the gene, so that after successful treatment with a degrader the patient can be retreated with a BTKi. In theory. If I find the source I'll add a reply.
Thanks for your valuable comments on this thread.
This is GREAT news ,. We are so lucky to be living in a time od BIG advancements.
Specking for myself, I'm way passed the "old sell by date". So, something else new is MORE good news.
Just grateful for every day. And taking it a day at a time.
Good luck to ALL of us
Michael
Hope for the best , prepare for the worst and take whatever god sends
I have appointments at UCSF and NIH Natural History Study in next three weeks. I will ask them about status of degrader trials and report back. UCSF has several degrader trials at the moment.
As MickUK mentioned, the FDA fast-tracked NX-5948 in Jan 2024. Here's an article about it from OncLive. onclive.com/view/fda-grants...
The FDA has granted fast track designation to the novel BTK degrader NX-5948 for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two lines of therapy, including a BTK inhibitor and a BCL2 inhibitor.
The investigational, orally administered, small molecule degrader was designed to bind to BTK and the cereblon E3 ligase complex. This results in the degradation of both wild-type and mutated forms of BTK.
Nurix has previously reported that NX-5948 is highly potent against a range of tumor cell lines with BTK inhibitor–resistance, which is an important consideration for heavily pretreated patients with CLL/SLL.
Additionally, NX-5948 demonstrated clinically meaningful on-target effects and tolerability in patients with relapsed/refractory B-cell malignancies in the dose-escalation portion of the phase 1 NX-5948-301 trial (NCT05131022). Preliminary data from this trial were reported during the 2023 ASH Annual Meeting and Exposition.
At the October 17, 2023, data cutoff, 6 patients in the CLL population (n = 7) who received doses of NX-5948 ranging from 50 mg to 200 mg experienced clinical benefit, 3 of whom achieved ongoing partial responses (PR).1,2 Moreover, 3 patients achieved stable disease, with treatment ongoing in 2 patients. Notably, all patients exhibited evidence of lymph node reduction.
NX-5948 was well tolerated across all dose levels. No dose-limiting toxicities, treatment-related serious adverse effects, or treatment-emergent adverse effects (TEAEs) that resulted in drug discontinuation were observed. There was no incidence of atrial fibrillation or hypertension.
“Fast Track designation for NX-5948 is an important recognition of the unmet patient need in CLL, particularly in the growing number of patients whose cancer has progressed following BTK and BCL2 inhibitor therapy,” Arthur T. Sands, MD, PhD, president and chief executive officer of Nurix, stated in a news release. “This designation follows encouraging safety and efficacy data from our ongoing phase 1 clinical trial, demonstrating early promise of clinical benefit with potential for durable outcomes.”
The first-in-human, dose-escalation and cohort-expansion NX-5948-301 trial is currently investigating the agent’s safety and clinical activity in adult patients with the following relapsed/refractory B-cell malignancies: CLL, SLL, Waldenström macroglobulinemia, mantle cell lymphoma, marginal zone lymphoma, follicular lymphoma, diffuse large B-cell lymphoma, and primary central nervous system lymphoma.
Patients aged 18 years and older with histologically confirmed, measurable or evaluable B-cell malignancies were included in the study. Other key inclusion criteria were an ECOG performance score of 0 or 1, and exposure to 2 or more prior lines of therapy.
The study employed a parallel 3+3 dose-escalation design. Notably, the phase 1b portion will include up to four expansion cohorts. Approximately 110 patients (30 in phase 1a and 80 in phase 1b) may be enrolled on the trial to receive oral NX-5948 once daily in 28-day cycles until disease progression or unacceptable toxicity.
The study’s primary end points in the dose-escalation phase were the incidence of dose-limiting toxicities and TEAEs, as well as establishing either the recommended phase 1b dose and/or the maximum tolerated dose. Primary end points in the phase 1b portion were safety and anti-tumor activity.
The study is actively enrolling patients across all indications in the United States, the United Kingdom, and the Netherlands. Additional data with the agent at higher dose levels and longer treatment duration are expected to be reported in 2024.1 The study has an estimated completion date of January 2027.
“The receipt of fast track designation is especially timely given our plans to accelerate enrollment in the phase 1 trial of NX-5948 with the goal of enabling a pivotal study for NX-5948 as rapidly as possible,” Sands concluded in the news release.
I had to look it up and used:
clinicaltrials.gov/search?t...
To get to research locations and criteria for USA
I'm super happy we have other option and glad they are looking to fast track it. Unfortunately it didn't work for me, but I am 17p and had been previously treated in two trials. This is the trial that I was in for 1 week and then ended up relapsing hard over. But glad to see it's working so well for others.
So sorry to hear it didn't work for you!
I really thought it was going to work, but my LDH went from 300 to 1000 and I lost 8 lbs between weekly check ins and that was that. But I'm good for now on V+P.
You are in my prayers that a new option may present itself. It sounds like you've been through a great deal already. I hope you can draw confidence, love, and support from this community. Never give up. Everyone's CLL is different, so I think , based on your unique features, it's gonna take different options to cure it. We have researchers fighting, on our side, from all different angles. Cancer will be eradicated one fine day. Heartfelt hugs & prayers to help you stay positive.
So sorry it didn't work for you and sharing your experience in light of this article is a valuable dose of reality for those weighing the merits. Thank you.
Don't get me wrong - I'm all for the clinical trials and I don't regret participating even in hindsight. But it's a reminder that not everything works for everyone.
Hello EastBayDad
This confirms what I have been reading for some time. It is good news for me as I have very aggressive CLL but currently in remission after V&O treatment. I do however have more breathing and fatigue issues than ever. Maybe very timely for me.
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