Acalabrutinib Achieved Breakthrough D... - CLL Support Assoc...

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Acalabrutinib Achieved Breakthrough Designation for CLL

This now fast-tracks Acalabrutinib (Calquance) for full FDA approval.

onclive.com/web-exclusives/...

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lily pad master. are you still taking the triple from dana farber?

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Indeed I am, yes. First official end-point for me is November. Just waiting for one pesky node to drop another 1 or 2 mm in size to be an "official" complete response, although I've been MRD negative for at least four months now. I remain on Acalabrutinib and Venetoclax. Obinituzumab was a time-limited addition.

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Lily pad master, may I ask how are you feeling on the Acalabrutinib Ven combo? What side effects if any from Acakabrutinib? I’ve heard weight gain, arthralgua and fatigue are common. I am seeing my specialist at UPENN tomorrow about treatment options. I am relapsed with high risk markers. I was on Ven for 14 months and was MRD negative for 6 months after stopping Ven. We are talking about btk inhibitors and I don’t want Ibrutinib.

Wishing you a long long durable remission.

Renee

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Hi Renee,

Same wishes for you! Feeling terrific, as I have since I began treatment. Low-grade thrombocytopenia. That’s it! Oh, Neuts went down for a little while. No biggie. Neulasta addressed it. U-Penn is terrific!

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Sooooo glad to hear you are doing great on Acalabrutinib! Do you see a specialist at UPenn? Mine gave me a bit if grief because I chose Acalabrutinib over ibrutinib, but, it’s my body and Acalabrutinib is supposed to be safer , less cardiac side effects. I will start in November. Any advice? Do you get fatigued? Have headaches when you started Acalabrutinib? I’ve read several posts by people taking Acalabrutinib and they all said headaches, nausea, and fatigue were their most common side effects in the first couple of weeks.

Renee

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Dang right it's your body! Good for you (even if you chose Ibrutinib instead). Information is power. My only advice it to prepare to start feeling better, fast! I noticed it within two days, and after four, my biggest neck node was visibly down by half. I was fatigued before treatment with Acalabrutinib, the opposite after my treatment started with about a month just on Acalabrutinib. I had some headaches, but those went away after a couple days and were manageable over a two week period. Drink lots of water and no Motrin!

I'm happy for you that you're about to start.

I'm seen at Dana-Farber. I just know that U-Penn is very good.

Glenn

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Glenn, thank you for sharing your journey with me! I feel very encouraged and less anxious about having to go back into treatment! I can’t wan’t for the feel better part and to stop living my life around the next blood test or pet scan. I am looking forward to having a future to plan for!

Smiling Now!

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This is big on a couple levels and raises a lot of questions. On the patient side of the equation, acalabrutinib should allow more people to benefit from btk inhibitors. As a front line therapy, ibrutinib works for just about everyone. The main problem with people getting off ibrutinib is intolerance to side effects, not that the drug stops working. Acalabrutinib is a more targeted btk inhibitor. In laymen's terms, that just means it has less side effects because it targets mostly just cll cells and doesn't target cells that cause us side effects as much. Acalabrutinib is a better btk mousetrap than ibrutinib, or it seems to be.

On the cll business side, this could be huge. Abbvie (J&J) makes ibrutinib. Its a block buster drug with sales approaching 7 billion, projected to be over 20 billion in years to come.

Aclabrutinib is made by UK pharma giant AstraZeneca (AZ). So what happens when acalabrutinib gets full FDA approval? Do doctors start people on it instead of ibrutinib? Will my doctor switch me to aclabrutinib from ibrutinib? Its going to be a marketing war between J&J and AZ. Unless they collude somehow, that's good for patients. Competition could drive the prices down. And it could make other pharma companies build an even better btk inhibitor.

Enter the Chinese. Yes, Cll does not discriminate, people of all races get it. Biogene is a Chinese based pharma company and it has its own btk inhibitor in clinical trials, zanubrutinib (just as most monoclonal antibody drugs end in mab, inhibitor drugs end in ib). Biogene claims Zanubrutinib to be more targeted than ibrutinib. Is it better than acalbrutinib too? Time will tell.

And then there is pharma politics. Will approvals be delayed or accelerated for reasons other than what drug works best? Who knows, we only know big pharma has a lot of money and its naive to think that lobbying money doesn't land in regulatory agencies like the FDA and the EMA (European Medicines Agency).

These drugs treat more than just cll, and that's good for us too. We want to be a big market cancer, companies spend more money in research and development for bigger market cancers, sad reality that might be.

I think the bottom line, politics and money aside, is this is all good news for us. The more tools our cll doctors have in the box to fix us, the more options we have. Competition among big pharma companies is good for us as well, unless big pharma companies collude on price (they do now and then), prices should go down.

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Interesting. Thanks Jeff

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Excellent summary of these BTK inhibitor medications (I A and Z) and who makes them CajunJeff! It is so important we know who makes these drugs and where they are in the regulatory approval chain so we can keep the agencies and big pharmaceutical companies honest. We need to let our Congress in USA know that as patients we are watching so if there is any unnecessary delays or on the flip side , our safety isn’t protected, we are ready to pounce as a group.

Thanks for informing us. There needs to be a balance here. Competition is good! It’s good for the world.

We need a post to list the makers of all these CLL drugs so we can follow the money. It keeps everybody honest.

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Some great points. Would also point out that while marketing is a driving force, there's also treatment strategy to consider; doctors or patients may value tried and true conservative treatment plans over something novel with limited history. Not directed to anyone in particular, it's important for a patient to be their own advocate these preferences should be voiced. Thanks for your valuable post!

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Yes indeed!

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i must point out a few things. Calquence has every single side effect Imbruvica has. Go to both sites and easily look up. There is also no proven evidence that it really has fewer side effects. There has been anedoctal comments in some studies by doctors that it seems less-especially for AFIB. However being a retired usa pharmacist i have seen this game from many me too drug reps. if ONE person less on a study had afib then on the other drug-the blaring out is causes less. You never see pronouncements how much less.

I also guarantee that when some people start first with calquence and have issues then will switch to imbruvica and be fine. the drugs are what they say-the reactions to them has the human being as the variable.

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Does anyone have any references to trial data for acalabrutinb? Probably not as it is not yet approved.

There must be a reason that the FDA gave “breakthrough designation” to this drug. If there was little to no difference between Acalabrutinib and Ibrutinib, then why bother? Then again this is merely conjecture on my part.

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the why bother is precisely why there are so many 'me-to' drugs for most diseases. a share of a big pie is still a lot of money. I went and read the 'release letter'. Calquence does every thing Ibrutinib does. However it's never been tested againt ibrutinib in a study. Neither company would fund one and take a chance theirs came out second best. Better to try a 'whisper campaign' than take that chance.

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I agree that acalabrutinib and ibrutinib have some similar side effects, they are both btk inhibitors and that is expected. I am not aware of anyone claiming acalabrutinib has no side effects, just that it is more targeted than ibrutnib with less side effects.

I do not agree with your statement that the only evidence acalabrrutinib is more targeted is anecdotal:

"The data have been encouraging, in that response rates and progression-free survival (PFS) seem similar to ibrutinib (Imbruvica) but with a better toxicity profile, so lower rates of atrial fibrillation, lower rates of bleeding, and less common arthralgias,” said Brown, the director of Chronic Lymphocytic Leukemia at Dana-Farber Cancer Institute, and a professor of medicine at Harvard Medical School".

onclive.com/conference-cove...

I dont agree the drugs have not gone head to head in clinical trials:

clincancerres.aacrjournals....

I do expect that there will be a turf war over btk drugs among big pharma companies and that we need to be aware that pharma companies can exaggerate and even manipulate data to their ends.

But that deosnt mean that some second generation drugs will not be better than the originals. In many cases they are, we are seeing that with new and better monoclonal antibodies like gazyva.

The biggest risk with ibrutinib is afib, and I think there is more than anecdotal evidence that acalabrutinib carries less risk of that. if I were someone starting treatment today with a btk ibhibitor and had any risk factors at all for afib, I would most definitely have a conversation with my doctor about whether I should do aclabrutinib over ibrutinib.

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if you reread my post i said nothing about targeting-just about less side effects. I also read the statement from doctor brown. I am always suspicious of studies funded by one company or another when comparing a drug to another as versus a disease.

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Unfortunately there is "researcher-bias" also. I do not doubt their integrity, but if some company is giving you a large "hand-up" in your research, then it could influence you psychologically. Also - you never bite the hand that feeds you!

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It’s as if people think a PI is the *only* person who sees, works with, or draws conclusions from data. Do people have any idea of how many team members participate in this, and just how dependent researchers are on internal and external processes to validate their findings? For every “cold fusion” TV broadcast there are literally tens of thousands of researchers at any moment who’s “psychology” is tempered by process. We pay cynical attention to that which stands out against the background noise of integrity instead of paying attention to the integrity.

I’m thinking that if you don’t trust your doc, gotta find a new one.

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No one doing research is perfect. There is always a bit of a bias - if only a flea on their shoulder - but a bias. Sorry, we're not robots who can be perfectly unbiased.

If someone or some company helps make your career, you don't trash them any more than you would trash your aunt Edna who sent you through college.

I highly doubt anyone skews trial data, but you will always have a soft spot for companies who helped make your career, even if you are now working on something that will help the competition.

Does that matter - no. Is there a conspiracy - no. If I needed treatment ASAP - I would run for Acalabrutinib. I'm sure the FDA was shown some very promising data - data that we have not yet seen. That's good enough right now.

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I read what you wrote. You wrote that there is only anecdotal evidence acalabrutinib has less side effects than ibrutinib. That’s not a correct statement as per the study quoted by Dr Brown. The study does show acalabrutinib has less serious side effects than ibrutinib. That’s not anecdotal evidence.

So now you write the study is unreliable and likely funded by a competitor. It might be, easy enough to check. But that’s different than what you first wrote.

You also wrote that there are no studies comparing the two drugs. That’s not correct.

I am certainly no expert and don’t know if acalabrutinib is superior to ibrutinib or not. I am suspicious of pharma companies too and agree they can manipulate data to their interests.

I am no expert for sure. I just respectfully disagree with what you wrote. There is more than anecdotal evidence acalabrutinib causes less serious side effects than ibrutinib. I think Dr Brown is better situated than you or I to judge if that data is manipulated. There are studies comparing the two drugs. Just saying.

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i would be interested in the study that compares acalabrutinib to ibrutinib head to head. could you provide a link. Thanks.

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Triple arm study withdrawn. One study, active in 2015, has still not recruited. Maybe it never will! You certainly could be right about the companies not wanting to go head-to-head. Also, in the article cited by CajunJeff, Dr. Brown never gave “her opinion” in an unqualified manner. She cited molecular and cell-line research that left her “expecting that...” or saying “I imagine that.” In no instance did the make an unverified claim.

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Jeff -this was not a clinical trial. do you know of an actual one

clincancerres.aacrjournals....

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Read your original post. You stated, as if it was a fact, and I quote, “it’s never been tested against ibrutinib in a study”.

I linked you to a study comparing the two.

I think it’s turned into a circular discussion at this point. The only reason I responded to your reply is we have people on here who could be considering acalabrutinib as a treatment choice.

I don’t think it’s correct to say there is only anecdotal evidence acalabrutinib has less serious side effects. I don’t think it’s correct to say the drugs were never compared in a study. I have nothing further of any help to the discussion. I could be wrong, it won’t be the first time today. But I did link to authority.

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you are correct. I should have asked if you knew of a 'clinical trial' that compared them head to head. I apologize for my imprecise wording.

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Anecdotal is good enough at this point. When the whole trial is revealed to the public, we can get into discussions like this. Right now, Acalabrutinib seems promising and that is a wonderful thing!

P.S. - the study you liked us to - I believe - is an in vitro study with cultured CLL cells.

That said, the data is still very positive for acalabrutinib. That's all that really matters. Hopefully there will be more good things to come.

When I was diagnosed 15 months ago, the only FDA approved drug (for first line treatment) was Ibrutinib. Now - just 15 months later - there are two more with promising possible drug combinations. The big picture is looking better and better.

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my point was how can you tell from cultured cells if someone or i should say how many would get afib .

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I don’t know the answer to that, and according to her article, neither does Dr. Brown. But, these are docs who ha e run Ibrutinib trials and are now running Acalabrutinib trials. The can see the difference in tolerance, but they can’t release more info until their data have matured.

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This is a head to head clinical trial pitting ibrutinib against aclabrutinib. It is sponsored by Acerta, who is partnered with Astra Zeneca on acalabrutinib.

clinicaltrials.gov/ct2/show...

Your assertion that neither company would risk funding such a trial appears to be incorrect. Will acalabrutinib have the same efficacy as ibrutinib with less side effects? We will know soon enough.

Its fair to assume Acerta/Astra Zeneca think so.

Hopefully the second and third generation btk inhibitors get better and better. That's good for you and me (and the rest of us on here). As Dr Koffman so often states in his signature line, we are all in this together.

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Hi Jeff. I saw this study and found it interesting that it's been open since 2015 but still hasn't recruited. Leaves me wondering about the kinds of challenges they're experiencing with it.

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am i misreading requirements does it say you MUST have 17p deletion or 11q and thats it?

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did you read what you have to have and what it's group requirements are. I think their trying to stack the deck-and they are running the study themselves

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I think just admitting you made a mistake in writing that neither manufacturer would sponsor a clinical trial comparing the two drugs would have been a better response than making an unsupported claim the trial is fixed. Clearly a manufacturer of acalabrutinib is sponsoring a large study comparing acalabrutinib with ibrutinb contradicting what you wrote. What am I missing?

I don’t understand how the trial requirements stack the deck. It’s a very large trial with over 500 high risk patients involved with both arms getting different drugs, one ibrutinib and one acalabrutinib. How do you conclude from that it’s a stacked deck? They are taking a big risk the ibrutinib arm does better. I think a reasonable expectation for Acerta would be that both drugs work equally well in controlling Cll, but the the acalabrutinib arm has less serious side effects.

In any event I am out of this debate. Facts don’t seem to matter.

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this looks to me like a 'small print' study. Ibrutinib came before acalabrutinib by x number of years. I suspect=but i can't prove that most bad side effects from ibrutinib came from 17p or 11q. A study limited to 17p and 11q would probably yield a study with favorable to acalabrutinib and still be perfectly honest. The large print would say one thing and the asterisk would say limited to 17p 11q. also this study is spread out worldwide. it may be 530 people spread out all over the globe. Since the makers of acalabrutinib are the central point for the info- i suspect if this study does not go there way it will not be published. This is a typical drug company ploy. You see asterisk stuff for all sorts of advertised drugs.

and to add one more thing what i meant in my initial post but was not clear on was a 'joint study' run by BOTH manufacturers. My apologies again for not being more precise

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I don't recall any of the early studies I read about Ibrutinib mentioning AEs (adverse effects) being more pronounced for those with more complex CLL. What would be the mechanism by which a kinase inhibitor, binding in a pocket of a protein, would have greater AEs for people with specific genetic markers in CLL cells but not in the non-CLL cells in which the Aesthetician's occur? What I do recall is that both Ibrutinib and Acalabrutinib show greater *relative* benefits for people with complex CLL in comparison to people with non-complex CLL, for whom FCR is still held to be a very viable treatment option.

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What is the issue here? If you’re on Ibrutinib and doing fine, awesome. If you’re on Acalabrutinib and doing fine, awesome. This is neither a football match nor “Nixon versus McGovern.” It’s a story about the federal government’s willingness to fast track a promising drug. Man. People complained when the FDA went too slow!

Dr. Jennifer Brown of the Dana-Farber Cancer Institute is going to bias her “opinion” (her science) because she’s funded by one company over the other? Wow.

Not to make this about me, because I’m not a medical scientist. But, I’ve been to seminars (and even a dissertation defense) at Dana-Farber/Harvard where a variety of people have explained the merits and pharmacology of this next-generation BTK inhibitor. Are you suggesting that these disparate researchers at a place that lives or dies by its reputation and integrity are all “shading the data?” These top scientists and translational medicine researchers have no need to “shop” their opinions to the highest bidders. And, yes, I’m aware that Dr. José Baselga failed to disclose all of his financial interactions. I’m also aware that out of the top ten NIH CCCs, CEOs, only two disclosed all of their financial relationships with Pharma. Both were women and one of those was Dr. Laurie Glimcher, CEO of Dana-Farber.

Skepticism is important, but even the educated take up conspiracy theories.

And, yes, I’m biased. Not specifically towards a drug. Just the people. I’d drop Acalabrutinib in a heartbeat if the data, so far, didn’t tell a compelling story.

An interesting question will be about whether people who don’t tolerate Acalabrutinib can subsequently respond to Ibrutinib.

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I have nothing against dr Brown. I was just wondering about what she based her conjecture on.

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Thanks re the reality testing.

Here's my summary from a post last May:

-ibrutinib stands out for atrial fib, blood disorder, mouth sores, acute interstitial nephritis;

-acalabrutinib stands out for gastrointestinal problems, bleeding/ easy bruising, fever;

-venetoclax stands out for rash/ skin prob, nausea, tumor lysis synd, fatigue/ dizziness.

I still consider it my goal to stay away from this stuff as long as possible.

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My view of the world is to ask, "Which one of these most likely would get in the way of my going to work or to a family birthday party?"

Each person is different -- as we keep saying -- but I do remember that I had NO side-effects on 8 infusions over 23 days of relatively inexpensive rituximab.

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what are your factors? I am p17 deleted and p53 mutated. they say chemo won't work on me.

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Have you been presented with options?

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13q mutated. When I was diagnosed in 2003, no one seemed to know what all that meant, but now, apparently, it is considered to be a good prognosis item. Rituximab in 2015 was a breeze for me, so I hope to have continued good luck.

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Dear Ivotedfornixon, I voted for him too! But I got over it :) Not bad to voice healthy skepticism on here. I just do not want to wake up to antagonism. When I woke up this am to read my cll posts, I wasn't sure where on the spectrum you were. For the anecdotal record: I went with acalabutinib, avoiding ibrutinib altogether. I based my decision on months of reading, some of which were research analyses, and some were physician reports of long term effects of ibrutinib on their patients. I wish I had a link for you of one particular doctor report that scared the heck out of me - it was a CLL Society link which I can't find. Before I made my decision, I avoided reading the patient reports because I felt that they would lean heavily on problems.

I do confess I liked Dr John Byrd's boiled down analysis most of all: “No drug is without adverse events. With ibrutinib, which is also a great drug, we tend to see more diarrhea, bruising, ecchymosis, and atrial fibrillation. With this drug, all of those adverse events were less. The side effects that stand out with acalabrutinib that are probably different from the other B-cell receptor inhibitors are some headaches, but they generally resolve; they’re not dose-limiting,” Byrd said in an interview with OncLive. As an acala user, I can report headaches. I control them 90% of the time with acetaminophin with caffeine. I've only been on it for 2 months, so I am no expert user. Time will tell. Hopefully, I'll have a lot of time to tell.

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Hi Fulart,

I had the headaches, too, for the first two weeks. I've probably had three or four over the ensuing 10 months. Each was eradicated by a couple glasses of water. Some neutropenia, but not certain that's from the Acalabrutinib. That, too, seems to be abating. I had been neutropenic, which my doc thinks was from the Obinutuzumab.

Best,

Glenn

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If my Imbruvica stops working i plan on asking for calquence(acalabrutinib) before i try something else. I have no doubts calquence(acalabrutinib) works as well as ibrutinib even if slightly different. I also have no doubts that some people will start on calquence-have issues-and try imbruvica and have it work for them. My point was NOT that Imbruvica was better than calquence. However in my experience in pharmacy over the years-just a slight edge in a side effect-even if just one percent-gets blown out of proportion. the variable is the patient usually-not the me to drug.

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Always love your very detailed and well-researched answers, Jeff! Keep going, we are learning a lot from you! ;)

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so what is the sticker price ?

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I shudder to think. Getting mine through a trial. Hopefully, when FDA approval comes and cascades around the world, costs will be manageable.

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going to be more then IBRUTINIB @ 12,000.00 a month, more then VENETOCLAX @15,000.00 a month

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$13,958 USD per Caremark/CVS per month.

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Yikes!

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caremark/cvs literally processes hundreds of plans which one

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I think we're talking list price here.

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Yes, list price.

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Hello Lily_Pad_Master

I think that is great news, means one more arrow in our quiver. Good to hear you are doing well.

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Thanks, Big_Dee! I’ll take as many arrows as I can get!

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I think that every possible point has been made in this thread. Fulart made a good point about not wanting to wake up to antagonizim here. The good news is that different drugs work well for different people and that we have more and more choices coming our way to chose from. Moving forward.......

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