Positive high-level results from the ELEVATE-RR Phase III trial showed AstraZeneca’s Calquence (acalabrutinib) met the primary endpoint demonstrating non-inferior progression-free survival (PFS) for adults with previously treated, high-risk chronic lymphocytic leukaemia (CLL) compared to ibrutinib.
The trial also met a key secondary endpoint for safety, showing patients treated with Calquence had statistically significantly lower incidence of atrial fibrillation compared to patients treated with ibrutinib. Atrial fibrillation is an irregular heart rate that can increase the risk of stroke, heart failure and other heart-related complications.1 Further hierarchical testing revealed no difference for Grade 3 or higher infections or Richter’s transformation. There was a descriptive trend for numerically favourable overall survival. Overall, the safety and tolerability of Calquence were consistent with the profile seen in the broader Calquence clinical development programme.
Let me preface this by saying I think there is mounting evidence acalabrutinib works as well as ibrutinib and has less side effects. If I were starting a btk inhibitor today, I would pick acalabrutinib.
Okay, that said, this is pharma wars on a huge level. Ibrutinib (made by Abbvie) is a 6 billion dollar blockbuster drug with sales projected to 30 billion in 2030.
Acalabrutinib (made be Acerta who was acquired by Astra-Zeneca) is the new kid on the block who wants to displace ibrutinib and grab some of those billions. Its like Pepsi taking on Coca-cola.
So the first thing I looked for, knowing the probable answer, was who sponsored the Elevate study showing acalabrutinib is superior? It was Acerta.
A few years ago there was a study showing ibrutinib did a better job of restoring our immune systems than acalabrutinib. That was an Abbvie study.
This is not to say Acerta/Astra-Zeneca designed their study in a way that favored acalabrutinib. there sure is a lot of money at stake and pharma companies have been known to do worse.
I tend to think it is a legit study, hopefully we will have more studies in the future with independent sponsors. I will not be shocked to see Abbvie fire back with a study showing ibrutinib is better.
It's a testament to the excellence of ibrutinib that this head-to-head trial took so long to produce results. Here's Dr. Byrd discussing (and successfully predicting results of) this trial at ASH 2015 with Dr. Koffman.
I think this is exactly what we expected and it's welcome that these results have been published BUT, and for me this is a HUGE BUT - this trial only recruited 17p and 11q del patients and the primary end point was simply progression-free survival in Arm A compared to Arm B at 36 months. There were secondary outcomes which also showed non inferiority at this same point thank goodness.
I would have liked to have seen all patients with all genetic types recruited to this study. I realise this would make it bigger and take longer but patients are disadvantaged by studies that only recruit a narrow cohort of patients. The reason for this is that it is then often only those same narrow groups that the treatment is approved for.
We can reasonably deduce that if this treatment is non inferior with the 17p and 11q del patients then it will be the same for other subtypes of CLL but there is now no evidence
Having said that these head to head studies are notoriously difficult to get off the ground, even when sponsored by the pharmaceutical companies. There is much more data to be mined from this study and I hope we get that nuanced information from the Pharma company to understand the differences between these two drugs as the follow up continues.
I suspect with billions at stake, Acerta designed this study in a way as best they could to make sure acalabrutinib looked good compared to ibrutinib.
If your competitor does a study finding their their drug is better than yours, you can always claim bias in the design of the study. If its your study of your drug vs a competitor drug, you are screwed if the other drug wins. This would have been devastating news to acerta/Astra Zeneca had ibrutinib outperformed acalabrutinib.
I have always been suspicious of the Abbvie study that found ibrutinib restores our immune systems better than acalabrutinib. It might be a valid study, I don't know. Its just that the competition between these companies for control of the btk multi billion dollar market is so hot, I take information coming out of either camp with a grain of salt.
The evidence does appear to be mounting, though, that acalabrutinib is the better mousetrap of the two insofar as drug toxicity is concerned.
Of course Jeff, they go for the easy pickings and follow the money doing the very patients that they are meant to bring benefit to, a huge disservice. 😞
Given Acalabrutinib's chief development medical scientist was behind the earlier development of Ibrutinib, I would be very surprised if Acalabrutinib didn't prove better overall. Sorry, I can't find the reference to the woman involved, but another member has mentioned this interesting fact a few times.
I suspect the research showing that Ibrutinib does better at restoring our immune system - specifically our T cell functionality, is correct. It's due to off target effects from what I've read.
That is good news but I'm sceptical regarding the drug pricing. They will fight for a piece of the cake but none will undermine the current price too much, as they want to pocket it not reduce it. Generics will be the only solution to the price extreme once the patent expires. As to 2030 sales projections, they may prove inaccurate now. Esp. if AZ or BeiGene takes market share from ABBV.
This is US specific I guess. Wow, from 26400 a year to 100K+ a year? Something is wrong with the system. Unless this drug is extremely difficult to manufacture drug makers will do it gladly for much less in other countries and supply the world for a reasonable cost. I at least hope so.
I used two different Ibrutinib generics in my country and i don´t see a big difference in price ( at least retail ) one is a Israeli genereci pharmaceutical the other a small local one... I don´t know if they charge less to the insurance, that i will be hard to get information .
I think that is great news. During trials on ibrutinib chances of a-fib or bleeding were about 12-14 %. As more and more people were prescribed ibrutinib that figure rose to 24 % who had a-fib or bleeding. I suspect this is due to not having people in trials who had medical preconditions. In this case I also suspect that the noted reduced incidence of a-fib between the two trials is very real. Thanks for info.
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