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Abiraterone’s approval is great news for men with prostate cancer – but why did it take so long?


Professor Paul Workman comments on the recent decision by NICE to approve abiraterone for men with advanced prostate cancer and offers thoughts on the drug approval process.

Posted on 29 March, 2016 by Professor Paul Workman

Abiraterone, trade name 'Zytiga', was discovered and developed at the ICR 

I am extremely pleased that after a highly convoluted process and several knock-backs, the pioneering cancer drug abiraterone has finally been recommended by NICE for men with advanced prostate cancer – earlier in the course of their treatment than was previously the case.

Abiraterone (now also known by its trade name of Zytiga) was discovered here at The Institute of Cancer Research, London, and its journey from our labs to patients is a great success story for British science.

ICR researchers were heavily involved in that path to innovation from start to finish, all the way from proposing novel inhibitors of androgen production as a treatment for prostate cancer, to designing and creating the drug molecule itself, through to recognising its potential in late-stage castration resistant prostate cancer and finally leading – in partnership with The Royal Marsden – the clinical trials showing how effective abiraterone is clinically.

This was difficult, painstaking and at times inspired research involving team science of the highest order.

The path to approval

We were of course delighted when abiraterone was first approved by NICE in 2012 for use on the NHS in men with advanced prostate cancer after cytotoxic chemotherapy – following its earlier regulatory approval by the US Food and Drug Administration (FDA), Health Canada and the European Medicines Agency (EMA) in 2011.

But already by then evidence was beginning to build that abiraterone could also be effective when given before rather than after chemotherapy. Getting access to abiraterone earlier in this way means that men are able to delay having to receive chemotherapy and avoid enduring its attendant side-effects for as long as possible – which has great benefits for their quality of life.

So the final approval decision from NICE is a good one, but the fact that it took so long for that decision to be reached is a matter that continues to cause concern.

This must surely have been one of the longest appraisals NICE has conducted. NICE began assessing abiraterone’s use before chemotherapy back in 2012, so it has taken more than three years to finally say yes. This delay has meant that men in England have lagged behind their counterparts in the US, Europe and, indeed, Scotland in being able to routinely access the drug pre-chemotherapy.

Why did it take so long?

Over the course of the NICE appraisal there was a huge amount of discussion about whether the use of abiraterone before chemotherapy was cost-effective.

When abiraterone was initially approved by NICE to be used after chemotherapy, the hurdle it had to jump to prove its cost-effectiveness – though by no means easy – was not so high. Because the patient population concerned had already exhausted most treatment options, including chemo, NICE was able to apply its less stringent end-of-life criteria, which made it easier for the drug to be approved.

But later on when considering the use of abiraterone pre-chemotherapy, NICE could not apply its end-of-life criteria – since this group of men can today expect to live for more than two years, thanks to innovative new drugs like abiraterone that are now available. As I’ve said before, it is surely illogical and perverse that abiraterone has found it so hard to be approved earlier in treatment – at least in considerable part because of our great success at keeping patients alive and well.

A tortuous path

So for abiraterone, the path to approval pre-chemotherapy has been a tortured one. NICE first announced its decision not to recommend abiraterone before chemo back in 2014, which it then reiterated in its final guidance. Later that same year, however, NICE paused its rejection decision and allowed the manufacturer Janssen to submit an amended Patient Access Scheme, which would bring the cost of the drug down as well as offering to reimburse the NHS for any costs after the first 10 months of treatment.  

Nevertheless, there was still a lot of uncertainty from the NICE appraisal committee about whether the drug was cost-effective, with the concerns seeming to hinge on the curves used in the economic modelling. The models predicted that some patients would remain on abiraterone for a very lengthy period – as long as eight years – and NICE was nervous that there was not at that time enough data on UK patients to support this extrapolation.

I would not by any means claim to be an expert in economic modelling and so I won’t go into the appropriateness of the extrapolation methods used by the company. However, clinicians at the ICR and The Royal Marsden do have great experience of treating patients with abiraterone and we know that some men do respond especially well. We call these patients ‘super responders’ and we do indeed know of one such patient who has been on abiraterone for more than eight years.

All this uncertainty led to yet another NICE decision to turn abiraterone down, followed by a further round of consultation, which we responded to – and now finally, at long last, a positive decision.

In its press release about the approval, NICE said: “When requested, Janssen submitted new evidence focusing on a large group of patients treated with abiraterone in the USA. The data showed that 14% of the patients were still taking abiraterone after 4.4 years. The appraisal committee expressed some concerns about whether these results could be generalised to the UK, but they recognised that the new data supported the case for some patients taking abiraterone for long periods of time.”

Overhauling the drug appraisal process

Of course at the ICR we are really delighted that abiraterone is now routinely available for men with prostate cancer in England – before chemo as well as after. It’s really fantastic news.

But at the same time it is very frustrating that it has taken such a long time. 

NICE does of course have a responsibility to achieve cost-effectiveness for the NHS, and it must take into account both the clinical benefit and health economics of a drug when conducting its appraisals.

But as I have blogged in the past it’s very clear that we urgently need to change our drug assessment system to ensure that it properly prioritises exciting, innovative and effective new medicines. Patients need to get the earliest possible access to such treatments. Abiraterone is one of these – the first in its class – and the delays to its approval very much demonstrate my point.

So I again urge NICE to implement the planned overhaul of its drug appraisal processes as soon as possible to avoid repeated delays in getting the best and most innovative treatments to patients on the NHS.

The best innovation comes from research leading to drugs that act on new, previously undrugged molecular targets – or from other novel approaches that tackle precedented targets in new ways. It is much riskier and more expensive to discover and develop drugs that have novel mechanisms of action than it is to produce modestly improved versions of what has already come before. If NICE does not give innovation the appropriate due recognition, then there will be no incentive for companies and academic institutions to create the genuinely novel treatments that can bring major step changes in cancer outcomes and survival. And in the long term, patients will lose out.

Let abiraterone be a lesson on why the system urgently needs to change.


abiraterone prostate cancer
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