Acalabrutinib Trial for COVID-19: forbes.com... - CLL Support

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Acalabrutinib Trial for COVID-19

Mldeterm profile image

forbes.com/sites/nathanvard...

46 Replies

ibrutinib is also mentioned .

Mldeterm profile image
Mldeterm in reply to

So much good info in that article. Even just on flu resistance study. Thankful for these drs like Dr Byrd.

This is amazing! Now I kind of regret being off of ibrutinib - stopped just as this pandemic began... which ibrutinib could perhaps mitigate worst results of.

From the article: "The cytokine storm that occurs in the pneumonia of these patients is heavily mediated by Bruton’s kinase and, unlike approaches that are trying to deal with one cytokine at a time, I see this [acalabrutinib/ibrutinib] more as a truncal intervention, in which you are basically hitting the central key pathway that regulates many of these cytokines so the rationale is incredibly strong . . . it gives us the opportunity to address the whole problem.”

I’ve read it like 25x. So much good in this article. What amazing drugs. Even the part about influenza. And the part about Dr Byrd having his staff research this. So very cool.

Yes in many survivors they mention drugs to control the cytokine storm which is what the BTK inhibitors do and other drugs that control inflammation?

Very cool. Not protection or a cure from covid 19 but help for patients tying to weather cytokine storms as they fight the virus.

The Italy piece hints at a thought of possible resistance or lower reaction but no proof of course and not a substitute for quarantine. Hope though! :)

And I just saw this which is a bit of a concern since we can only get one month at a time:

In the meantime, he <Byrd> is exceptionally concerned about the limited supply of BTK inhibitors for chronic lymphocytic leukemia patients who need these drugs to survive.

Agree. I’m suspecting if there is profit involved they will find a way to mass produce quickly. Glad he is calling this out though. My husband is on a combo trial with I+O+V and stops in October so he gets it 3 months at a time but he’s nearly finished.

Of course, the potential downside for us CLLers is this:

"In the meantime, [Dr. Byrd] is exceptionally concerned about the limited supply of BTK inhibitors for chronic lymphocytic leukemia patients who need these drugs to survive."

Ibrutinib and Acalabrutinib supplies, which are limited, could in a pandemic be redeployed to those whose need is seen as more urgent.

Wow, that would be terrible for all of us taking them.

Cool info , thanks for sharing

Great for people on it but as far as it being given to the masses; no way. Too expensive.

Jeff

Mldeterm profile image
Mldeterm in reply to Justasheet1

Its expense lies in the length CLLers take it. I would not think that would be the case with using it for COVID recovery? Not cheap but not the same as taking it for years like we do.

Justasheet1 profile image
Justasheet1 in reply to Mldeterm

Agreed. I guess we’ll see.

swim_lifer profile image
swim_lifer in reply to Mldeterm

At a retail price of approximately $500 per day, these are expensive drugs even for short term .

bhayes84 profile image
bhayes84 in reply to Justasheet1

I don't think what the charge has any relationship to the actual cost of production. They would claim that most of the price goes to recouping the cost of development and drug trials.

If someone knows otherwise please correct me.

I have a complaint for Newdawn, Jackie, Neil and other administrators of this site. I tried to give thos post ten thumbs up and it only let me do one. Lol

It would be pretty awesome if ibrutinib and acalabrutinib also treat covid. And wonderfully ironic. I have been worried me taking ibrutinib makes me more vulnerable to covid. Now there is reason to believe it makes me less vulnerable? Lol. This is a trial I’ll be watching. Frick covid, sorry for my french. 😎

I just hope doctors don’t start prescribing it off label and create shortages.

It would be cool if generic was forced to come early...

Ten likes would be no likes. You must have tried 11.

Jm954 profile image
Jm954Administrator in reply to cajunjeff

I agree, it feels like a little strand of hope for those of us on these drugs already. It would be brilliant if everyone who needed it in ICU could have it too.

Jackie

Since it's hard to administer because the patients are on ventilators, maybe they should try rituximab, which is injected and also anti-inflammatory. Coincidentally, like hydroxychloroquine, also taken by lupus and rheumatoid arthritis sufferers.

Mldeterm profile image
Mldeterm in reply to randomacts

I told my husband to take his ibrutinib with a coke for good measure to emulate the study. Coke of all things?!

This is a very interesting and hopeful article thanks for sharing.

But I would say a couple of crucial points. Firstly someone already on ibrutinib or acalabrutinib should NOT assume this means that they can’t get COVID19 or even that this drug will definitely protect them if they do. For all of us with CLL it remains an important precaution to strictly self isolate and ensure we cannot catch this disease.

It’s important to understand that the cytokine storm is only one way a disease like this can cause serious complications. And in these very small number of case studies in people with otherwise intact immune systems it does sound like maybe this may possibly be helping. But don’t forget these people have intact immune systems. For us who all have a sub optimal immune system this approach may or may not be helpful.

It is great that they are also doing an actual clinical trial complete with control group. Sounds like anyone already ventilated can have the drug in the trial and those at risk of ventilation will be randomised to get it or not. It sounds like if these drugs are indeed useful then they would likely only be useful in the stage when the immune system is over active.

It is interesting to also reflect that in the COVID case with CLL from China who got sick and recovered they actually started chlorambucil a form of chemo during that patients CLL disease. Perhaps that drug also helped to dampen down the immune response.

One observation that’s been noted with patients with COVID19 is actually lymphopenia which on its own would make you wonder whether an anti CLL drug would work.

To conclude from what I’m reading it seems that there are sometimes two phases of this illness. In the first phase you want the immune system if anything to be stimulated. You want it to fight off the disease. This is a phase when we might well be at a disadvantage.

The second stage is when a sub group of patients find their immune system actually goes into over drive and a citokine storm arrises and in effect the body and particularly the lungs effectively experience co lateral damage. This is the phase where you’d perhaps want to try and “damp down” the response. At this stage we don’t really know if patients with CLL are more or less likely to suffer from the citokine storm. Certainly some people with CLL do get this in response to other infections.

So in short this is very fascinating data but preliminary. And due to our other defects in our immune system I don’t think it means we should relax our hibernation rules just yet even if we are already taking ibrutinib or acalabrutinib.

I hope everyone is managing to cope with cabin fever. And hopefully most of us are less worried about catching COVID19 since so many of us have now been separated from humans who could give us the disease for more than 21 days now.

We are all in this together.

BluMts profile image
BluMts in reply to AdrianUK

Adrian, don't think any of us who've read the reports\news have thought being on IB or Calquence would protect us from getting this virus or any virus.

😆

AdrianUK profile image
AdrianUK in reply to BluMts

I was just checking. There is a theory floating around even being mentioned by some specialists that having CLL might not be as risky as we currently think it is with COVID19. I’m afraid I’m a big believer in stating the obvious with not just those who write on here in mind but the many who simply read and might find certain posts or comments confusing.

BluMts profile image
BluMts in reply to AdrianUK

Fair enough Adrian. Understood.

Jm954 profile image
Jm954Administrator

Thanks for this, which is important information.

More information from the site copied to here (partially redacted):

.

British drug giant AstraZeneca is rushing forward a big clinical trial for its blood cancer drug Calquence because it has shown early promising results in later-stage COVID-19 patients—those in intensive care units and on ventilators. Calquence and top-selling leukemia drug Imbruvica are the latest hopes in getting coronavirus patients off ventilators, where there is a 50% mortality rate.

Some of the severely ill COVID-19 patients who received Calquence, which is also known by its generic name acalabrutinib, were materially helped by the drug, people familiar with the matter say.

One of the most serious medical issues of the current pandemic is how the immune system of people infected with SARS-CoV-2 fights off the virus. Some COVID-19 patients have become critically ill or died after cytokine molecules in their bodies sparked an out-of-control immune response (or cytokine storm) that damaged the lungs or caused acute respiratory distress syndrome (ARDS), which floods the lungs with fluid.

Calquence and Imbruvica are known as Bruton’s tyrosine kinase (BTK) inhibitors because they block the BTK protein that is key to the signaling of white blood B cells of the human immune system into action. These drugs have proven to be especially effective in patients with chronic lymphocytic leukemia, but they also have an anti-inflammatory benefit like arthritis drugs.

“The science of acalabrutinib and, I think more than that, of Bruton’s tyrosine kinase situation, is pretty strong. The mechanism is very clear,” said José Baselga, the head of oncology research and development at AstraZeneca.

“The cytokine storm that occurs in the pneumonia of these patients is heavily mediated by Bruton’s kinase and, unlike approaches that are trying to deal with one cytokine at a time, I see this more as a truncal intervention, in which you are basically hitting the central key pathway that regulates many of these cytokines so the rationale is incredibly strong . . . it gives us the opportunity to address the whole problem.”

Early last week, AstraZeneca formed a COVID-19 task force after receiving early data regarding patients given Calquence by the NCI. Baselga said that within 72 hours the company had completed drafting a COVID-19 clinical trial and submitted it to the FDA, the fastest study he has ever seen put together in his 30-year career. Such an effort would normally take more than three months.

.

stay safe, stay home

Jackie

who is just going out into the garden :)

WOW! Thank you for sharing. Makes me longing for starting Acalabrutinib or Ibrutinib as soon as possible, to take control of my CLL/ITP!

All these fabulous doctors thinking and striving! They are fantastic.

Hello Mideterm

The patent for Imbruvica expires in 2026. Hopefully it will get cheaper with wider use as well.

in reply to Big_Dee

the 2026 patent is USA. most countries have their own patent rules.

Big_Dee profile image
Big_Dee in reply to

Hello Ivotedfornixon

Yes, that is one of the reasons US companies sell their drugs at cheaper prices outside of US, because it reduces incentive to copy drugs to work around patents.

So much irony . Great news that this may help against Covid, bad news that we may have to fight for the medication that has been keeping us alive!

Virginia

That would be very scary if we were unable to secure the medicine we need that helps so

many people with CLL lead a relatively normal life.

"Byrd also heard an anecdotal report from a doctor in northern Italy, where the healthcare system was overwhelmed by COVID-19 patients, that most of his elderly chronic lymphocytic leukemia patients who were taking Imbruvica as part of their normal course of treatment were not showing symptoms of COVID-19. Being immunocompromised, those patients were under strict orders to self-isolate, but there was a chance that there was something else going on related to the medications they were taking. "

I'd like to see everyone on ibrutinib or acalabrutinib tested for COVID-19 (infection or antibodies) to see if there is any truth to this anecdotal report from Italy.

WOW! I wonder what that means for the people like my husband who are already on Calquence and doing well?

Mldeterm profile image
Mldeterm in reply to skunkbay53

My husband is on ibrutinib (first generation of Calquence) and my takeaway is just that these are incredible drugs and we're so lucky to have drs like Dr Byrd. No plans to lessen our approach to quarantine but great hope that these drugs are helping one's immune system whether that translates to COVID protection/result, Flu, Pneumonia or otherwise.

-Mindy

think about the amazing symmetry of someone seriously ill with COVID-19, a disease first diagnosed in Wuhan, China, saved by ibrutinib, a drug made in Wuhan, China.

MSKCC also has a trial of BTKi for COVID-19 so I assume there are, fortunately, multiple cancer centers involved in the research. Incidentally, Zanubrutinib is also on the list.

Amazing . I wonder about the dosage they will be given. Hopefully if given Ibrutinib they won't experience the beginning side effects. They are so sick to begin with, however like us it will save their life.

avzuclav profile image
avzuclav in reply to country76

Good question on dosage. It's not listed on the trial web page. clinicaltrials.gov/ct2/show...

Justasheet1 profile image
Justasheet1 in reply to avzuclav

Avz,

It mentions singularly,

“Drug: Acalabrutinib

Acalabrutinib- administered orally or receive delivery of emptied capsule via a nasogastric (NG) or an enteral feeding tube“.

You could possibly infer only one capsule?

Jeff

avzuclav profile image
avzuclav in reply to Justasheet1

I think you are stretching to make that inference! Then again I'm on one capsule... twice per day.

By the way maybe this is what happens when they rush trials - forget minor details such as dosing, etc.

This is a good read of a Doctor who survived covid-19 after a life threatening

Case

latimes.com/world-nation/st...

Good article, so I went looking for a venetoclax (BCL-2 inhibitor) related article about reducing airway inflammation for lungs, found one related to athsma...

sciencedirect.com/science/a...

This is interesting news, especially as in the past few days I'd been reading up on ARDS, triggered by viral infections: the processes, cells, molecules involved.

Why the interest? Of the 20 percent of Covid 19 cases who develop severe symptoms, Acute Respiratory Distress Syndrome affects 30-45 percent of them, and once you have ARDS your statistical chance of survival is no better than 50/50.

It cost me an hour or two's sleep trying to reconcile my recent reading with Astrazeneca's BTK rationale for Alcalabrutinib, as a treatment for severe Covid. I couldn't, because the evidence implicates NEUTROPHILS as the main culprit in the potentially lethal lung damage caused by ARDS. Platelets and monocytes also have a role. That being so, any drug that reduces neutrophils etc far enough, fast enough would do the trick. So not just CLL patients on Ibrutinib or Alcalabrutinib, but all of us with low blood values, could share an advantage in severe Covid.

However...

Please please please, shield shield shield!

No news on the CALAVI study (acalabrutinib for COVID), but the huge WHO Solidarity trial is soon adding acalabrutinib and is accruing 2000 patients/month. Maybe we'll hear more soon.

"As early as next week, Solidarity participants could start receiving acalabrutinib, a cancer drug that inhibits an enzyme that plays an important role in the human immune system."

sciencemag.org/news/2020/10...

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