NICE Recommends Acalabrutinib for treating CLL for certain groups

[Jm954]

NICE has approved Acalabrutinib as monotherapy and is recommended as an option for untreated chronic lymphocytic leukaemia (CLL) in adults, BUT ONLY IF:

* there is a 17p deletion or TP53 mutation, or

* there is no 17p deletion or TP53 mutation, and fludarabine plus cyclophosphamide and rituximab (FCR), or bendamustine plus rituximab (BR) is unsuitable, and

* the company provides the drug according to the commercial arrangement.

Acalabrutinib as monotherapy is also recommended, within its marketing authorisation, as an option for previously treated CLL in adults.

NOTE: These recommendations are not intended to affect treatment with acalabrutinib that was started in the NHS before this guidance was published. People having treatment outside these recommendations may continue without change to the funding arrangements in place for them before this guidance was published, until they and their NHS clinician consider it appropriate to stop. This last note is for anyone who had Acalabrutinib as part of the access programme during the covid pandemic or as part of a clinical trial.

Why the committee made these recommendations

This appraisal looks at the use of acalabrutinib as monotherapy. NICE has not made recommendations on the use of acalabrutinib with obinutuzumab because the company did not submit any data for this combination.

People with untreated CLL that has a 17p deletion or TP53 mutation usually have ibrutinib. For this group, acalabrutinib has not been directly compared with ibrutinib in a clinical trial, and the results of an indirect comparison are uncertain. The company assumed that acalabrutinib is as effective as ibrutinib in a cost‑minimisation analysis. Despite the uncertainties, acalabrutinib is likely to be cost saving compared with ibrutinib. Therefore, acalabrutinib is recommended in this group.

People with untreated CLL without a 17p deletion or TP53 mutation usually have FCR or BR. If FCR or BR is unsuitable, chlorambucil plus obinutuzumab is offered instead. Clinical trial evidence in this group shows that CLL takes longer to progress when treated with acalabrutinib compared with chlorambucil plus obinutuzumab. However, the overall survival benefit is uncertain. The cost-effectiveness estimates are within what NICE normally considers an acceptable use of NHS resources, so acalabrutinib is recommended in this group.

People with previously treated CLL that has relapsed or does not respond to treatment, usually have ibrutinib or venetoclax plus rituximab. For this group, acalabrutinib has not been directly compared with ibrutinib or with venetoclax plus rituximab. The results of an indirect comparison with ibrutinib are uncertain. The company assumed that acalabrutinib was as effective as ibrutinib in the cost‑minimisation analyses. Despite the uncertainty, acalabrutinib is likely to be cost saving compared with ibrutinib. Therefore, acalabrutinib is recommended in this group.

As a charity CLL Support are disappointed that Acalabrutinib was not approved for all patients as a first treatment but the company did not request approval for all patients and no evidence was presented for consideration. We will continue to advocate for access to novel treatments for all patients for first treatment to prevent the health inequalities that are starting to develop between younger, fitter patients who have limited access to a novel therapy therapies and older, less fit patients who now have a range of choices.

Jackie

[annmcgowan]

Hi Jackie thank you for the update and all the work you do on our behalf.Take care

Ann

[Walkingtall62]

Thanks Jackie. One good thing to come out of Covid for me! I was put on Acalabrutinib !

[BluMts]

Thanks for this as I'd read in the press that Acalabrutinib had been approved by NICE for treatment of CLL patients in the UK. As there were no qualifications I thought any CLLer could get this treatment.

[mrsjsmith]

Thank you for all your hard work Jackie.

Regards

Colette x

[Peggy4]

Good news and thank you Jackie for your hard work.Peggy.

[Ernest2]

Thanks Jackie for all your hard work.

Best wishes,

Ernest

[Smith123456]

the company provides the drug according to the commercial arrangement. what does that mean?

[Jm954 Administrator in reply to Smith123456]

It means it is supplied at an enormous discount for the NHS and if it is not then the NHS won't use it.

[Smith123456 in reply to Jm954]

if the company did not request-maybe they want to limit the amount of cut rate drug they supply?

[Jm954 Administrator in reply to Smith123456]

The company requested the approval from NICE and also agreed the discounted price

[cajunjeff in reply to Smith123456]

I do not know but I would assume that Astra Zeneca is the "company" and the "commercial arrangement" is whatever deal they have struck with NHS or whoever is paying for the drug as to the cost of Calquence.

Moreso to that point, it appears Astra Zeneca is undercutting Ibrutinib on price, which might have helped them get the approval.

Many think acalabrutinib is a better drug than ibrutinib anyway due to less side effects. Maybe this will all help lower ibrutinib costs.

[Smith123456 in reply to cajunjeff]

Jeff-i was a retail pharmacist for a long time. In drugs when a brand name begins to lose market share-they raise the price of the drug. Drug pricing is considered inelastic. Since a patient cannot directly buy drugs-they need a doctor to write the prescription. the drug companys constantly lobby until their patent runs out. Then the jack up the price even more

[cajunjeff in reply to Smith123456]

I guess we have a different view of this, typically what happens when a patent runs out the generics move in and the price plummets. That has little to do with ibrutinib and acalabrutinib we were discussing though, they are competing drugs both still under patent and the article Jackie supplied suggests that the NICE approval of aclabrutinib is in part die to the fact that its cheaper than ibrutinib and that Astra Zeneca cut them a better deal.

One way pharma companies keep their prices high was they approach patent expiration is to pay the main generic manufacturers to delay the generic equivalent in a questionable practice known as "pay for delay". I know more about pay for delay than the average bear as I have been very involved in efforts to expose it as a scheme to keep drug prices high.

The ibrutinib patent expires in 2026. From what I understand NHS is very cost conscious. The market for a front line btk in the UK would be enormous. Since ibrutinib and acalabrutinib are both effective, when and if they get broader approval for front line treatment, we could see the price go down as they lobby to be the NHS drug of choice.

[Smith123456 in reply to cajunjeff]

the price plummets for the GENERIC. The BRAND NAME manufacturer raises their price. there are some patients who want Brands. Sometimes the brand manufacturer will make deals with different health providers. Sometime the Brand name manufacturer sells their product to the generic manufacturers. Sometimes the Brand name manufacturer sells both. They sell the brand at a high price and sell the generic at cut rate prices. That is ALL legal by the way.

However-all the things i say-and you say-have involved lower cost drugs. the drugs we use are "orphan Drugs". special rules apply to them. given both by usa and socialised medicine countries.

[Jm954 Administrator in reply to Smith123456]

It's not true that they are necessarily orphan drugs as many of these drugs such as Ibrutinib, Acalabrutinib and Venetoclax are used in other diseases too. Using them in all B cell disorders and AML gives them a wide reach and more potential profit so they don't qualify for orphan drug status, at least not in the UK.Jackie

[cajunjeff in reply to Smith123456]

I do not disagree with some of this, but it has nothing to do with my original comments. The manufacturers of ibrutinib (janssen) and acalabrutinib (astra-zeneca) are fighting over a giant market for blood cancers. They want the broadest approvals they can get and approval by health care systems like medicare and NHS are critical to their market share.

The NHS has been slow to give ibrutinib approval for frontline cll cases but for 17p cases, which are not common at diagnosis. Jackie's post includes this language:

The company assumed that acalabrutinib is as effective as ibrutinib in a cost‑minimisation analysis. Despite the uncertainties, acalabrutinib is likely to be cost saving compared with ibrutinib. Therefore, acalabrutinib is recommended in this group.

All I wrote was that astra - zeneca was undercutting the cost of ibrutinib and that cost savings influence NICE.

Your reply seems to say that this will cause Janssen to raise prices and you seem to see this as an old drug (ibrutinib) vs a generic (acalabrutinib).

Acalabrutinib is not a generic of ibrutinib though, its a second generation btk inhibitor, a better mousetrap some would say.

So it makes zero sense that the strategy for Janssen (ibrutinib) in reaction to lower priced acalabrutinib (Astra Zeneca) would be for Janssen to raise prices as you say. Its not a situation where ibrutinib is losing market share to a generic.

[Smith123456 in reply to cajunjeff]

the brand name company raises prices to make up for loss of market share-simple as that. thats the awp-average wholesale price. You are talking apples and oranges. acalabrutinib is making deals. ibrutinib can make deals if they want. acalabrutinib's superiority with side effects makes it the preferred drug.

[cajunjeff in reply to Smith123456]

You have ignored what Jackie posted and I quoted in me trying to answer your question. The article says acalabrutinib is cost saving compared to ibrutinib and then concludes acalabrutinib is therefore recommended. It’s quite clear it’s not only the effectiveness of acalabrutinib that got it recommended but also that it is cost saving.

It seems you disagree with the author. I am just repeating what is written.

[Smith123456 in reply to cajunjeff]

if imbruvica brought their price down to the same as acalabrutinib which one would be chosen? the superior drug of course acalabrutinib. So imbruvica cannot win in price match.ing. It has to be LESS than acalabrutinib. So acalabrutinib just price matches ibrutinib. Ibrutinib cannot win. Thats why Brand Name manufacturers RAISE their price. they want to maximize the dollars the get for whatever prescriptions they get. they cannot win a price cutting war against a superior drug. in fact i can make the same issue with usa generic drugs wen patent expires. A brand manufacturer in the usa can never win in a pricing war with a generic. Thats why the brand name raises the price. It wants the most dollars from whatever prescriptions it can still get. Now do they do other tricky things-sure. But raising the brand price is the first step.

[AussieNeil Partner Administrator in reply to Smith123456]

Typically, the market for CLL drugs has been too small to see price competition, but there is intense competition in the BTKi drug field, aided by the wider application of this class of drug than just CLL. See: healthunlocked.com/cllsuppo...

Ibrutinib has the downside of a greater side effect profile than the newcomers, some of which will work when Ibrutinib resistance develops. Yet Ibrutinib has the advantage of far more patient data - both in length of time patients have been on the drug (approaching 10 years) and patient numbers.

Rituximab is an interesting comparison in this regard. It retains a strong market position despite competition from better later generation versions, such as Obinutuzumab and Ofatumumab.

What is most interesting in this regard is that BTKi suppliers are now in the position of negotiating deals for large new markets with country health organisations in the UK, Australia, Canada and elsewhere, something which pharmaceutical companies successfully lobbied to prevent in the USA. Interesting times, which should at last help many of us gain affordable access to far better drugs than are currently available to us!

Neil

[Jm954 Administrator in reply to Smith123456]

But we are not talking about generic drugs here. Janssen didn’t ask for first line approval from NICE and now they cannot afford to come into the first line market in U.K. because of the price difference with Acalabrutinib. They would also probably have to reduce their price for the RR and TP53/17p markets which they don’t want to do.

Jackie

[Smith123456 in reply to Jm954]

i added the generic drug stuff since i made the post. all at once

[Jm954 Administrator in reply to Smith123456]

Not sure what you’re saying here

[Jm954 Administrator in reply to cajunjeff]

Exactly Jeff

[Beattiem-UK]

Thank you for that Jackie.

[Beattiem-UK]

And thank you Jeff.

[Jacksc06]

Thank you for the update Jackie, Your hard work is much appreciated. Best wishes.

[AutumnJ]

That will be disappointing for some, including me!Thank you for your continued work and advocacy on our behalf 🙏🏼