First test case of NICE approach to Highly Specialised Technologies – Soliris® (eculizumab)

In the first test for the new Highly Specialised Technologies (HST) process for the UK’s medicines cost effectiveness watchdog NICE, Leela Barham analyses the situation with Alexion’s Solaris, for treating atypical haemolytic uraemic syndrome.

Continued from ‘Rare disease reimbursement needs a reasonable process, not a blunt rule’.

In England the National Institute for Health and Care Excellence (NICE) has a new responsibility to assess Highly Specialised Technologies (HSTs), which are basically drugs for really rare diseases. Its process has been set out in interim guidance, but hasn’t yet been tested. But the move to NICE has been controversial with concerns about the focus on the cost per Quality Adjusted Life Year (QALY) trumping solidarity. The first drug to go through will be a real test for NICE as it has had a controversial start; it was recommended by NICE’s predecessor in assessing ultra-orphans, the Advisory Group for National Specialised Services, but Ministers referred it on to NICE in what amounts to a lengthy and multiple assessment.

About Soliris

Soliris (eculizumab) is a treatment for atypical haemolytic uraemic syndrome (aHUS) developed and marketed by Alexion. aHUS is a very rare disease, with around 140 patients diagnosed in England. The consequences for patients range from premature death (25% die from the first attack despite the best treatment available before Soliris) and life long kidney dialysis. As NICE notes, “People with aHUS may experience a considerable impact on their daily living and quality of life and can experience significant kidney impairment, thrombosis, heart failure and brain injury“. Whilst Soliris can’t cure aHUS, it prevents progression of it.

“The first drug to go through will be a real test for NICE as it has had a controversial start”

The AGNSS assessment

AGNSS was a relatively short-lived agency; it existed from 2010 and was closed down as part of broader reforms to the National Health Service (NHS) in March of 2013. Its demise was a concern to both clinicians and to patient groups like the Niemann Pick disease group and Rare Disease UK. Part of the concern was the move to NICE would see too much emphasis placed on cost per Quality Adjusted Life Years (QALYs); these are quite simply often very high for orphan drugs. That’s a function of the basic economics: it costs a lot to develop and bring a drug to market and if there are few patients to sell it to, the unit cost will be high. But that could lead to NICE saying ‘no’ more often than it would say ‘yes’ to these types of drugs.

The AGNSS approach can be broadly characterised as Multi-Criteria Decision Analysis as it set out a decision-making framework with 4 main criteria (with sub-criteria within them):

1. Does it work?

2. Does it add value to society? Both in terms of stimulating research and innovation and meeting the needs of patients and society

3. Is it a reasonable cost to the public? This included overall cost impact and affordability including opportunity cost, and value for money compared to alternatives

4. Is it the best way to deliver the service?

But what it didn’t do, and I’ve yet to come across an agency that has in relation to medicines, is set out just how much weight rests on each criterion in order to generate an overall ‘score’ for a drug that will then translate to a recommendation to reimburse or not. And with only 2 recommendations actually put in the public domain (the other being for Tafamidis for the treatment of familial amyloid polyneuropathy (FAP)) it’s hard to glean how far affordability and cost effectiveness (which in the case of rare can be low in budget impact terms, yet high in cost per Quality Adjusted Life Year terms) trump the others even after the fact. Especially when AGNSS took out all but one of the cost per QALY estimates produced for Soliris, citing commercial sensitivity. (But they are available in an NHS England commissioning policy).

AGNSS took the view that Soliris should be commissioned back in June 2012, but also said that the “Department of Health and the NHS Commissioning Board [now known as NHS England] should take steps to negotiate the cost of Eculizumab“. That suggests that whilst the clinical evidence was considered compelling (Soliris was considered near the “top end of clinical effectiveness“) there was still a question about the price that the NHS should pay in the minds of the Advisory Group (with the cost being £164,430 for 6 months the cost is high). The Advisory Group even went as far as suggesting a cap be placed on the cost of treatment.

“The tricky issue about affordability is simply whether or not there are more patients that could be diagnosed”

The Minister’s decision

According to AGNSS, Ministers agreed that “there is evidence for the clinical effectiveness of Eculizumab for the treatment of atypical haemolytic uraemic syndrome“, but wanted “further advice on affordability“.

Hence the decision to put Soliris into the HST process at NICE. But part of the tricky issue about affordability is simply whether or not there are more patients that could be diagnosed – it’s so rare that many doctors may miss it when patients present with symptoms. With a further 140 patients potentially out there across England to treat the budget impact could increase. Not only that but also whether Soliris is prescribed before dialysis is required so avoiding the costs of dialysis and kidney transplants, both good for patients and good for the NHS by avoiding expensive hospitalisation.

The NHS England interim funding decision

Although not explicitly stated as so, there is a stop-gap approach when drugs aren’t yet fully assessed. In the case of Soliris, NHS England, as the agency now responsible for commissioning specialised services, said in September 2013 it would fund the drug. NHS England said it would fund the drug for those newly diagnosed and for those who are suitable for kidney transplant. Those who aren’t suitable for a kidney transplant will be subject to ‘commissioning with evaluation’. But NHS England won’t be paying “for patients currently diagnosed with aHUS who have not received approval for Eculizumab from an existing commissioning body“. So not everyone is getting it: media reports suggest around 20 a year are getting it.

The NHS England commissioning policy is however only to cover funding whilst the NICE guidance is being developed. Their decision will be reviewed when NICE guidance comes out.

The NICE assessment

NICE is currently looking at Soliris using the criteria set out in its interim guidance:

• Nature of the condition

• Impact of the new technology

• Cost to the NHS and personal social services

• Value for money

• Impact of the technology beyond direct health benefits

• Impact of the technology of the delivery of the service

But the NICE process does take a long time: a recommendation is expected in July 2014.

“There is no doubt that the final recommendation for Soliris will be closely looked at”

Multiple assessment and considerable delay

All together Soliris will have been considered by AGNSS, by NHS England and by NICE. It also means that the NHS will have been cogitating over Soliris for almost 7 years since it was authorised in June 2007 for the treatment of paroxysmal nocturnal haemoglobinuria and more latterly for the treatment of aHUS in 2011 (although the NICE process will be a very small part of that delay). And all of this takes time and money. And just how will it be justified if NICE take a different view to both AGNSS and NHS England? Especially since they’re all pretty much looking at the same evidence base.

Will concerns about NICE and HSTs be proved right or wrong?

There is no doubt that the final recommendation for Soliris will be closely looked at: not just by those directly affected (clinicians who want to prescribe, patients who want to benefit from the drug, and the manufacturer who wants to recoup their R&D and make a difference to lives) but also by a wider contingent. Over 10,000 signed an e-petition to approve funding without delay. Some have even argued that the step to basically delay a decision due to affordability concerns is a much more fundamental break from underlying NHS principles. So the Soliris recommendation due from NICE is definitely one to watch.


About the author:

Leela Barham is an independent health economist and policy expert who has worked with all stakeholders across the health care system both in the UK and internationally. Leela works on a variety of issues: from the health and wellbeing of NHS staff to pricing and reimbursement of medicines and policies such as the Cancer Drugs Fund and Patient Access Schemes. Find out more here and you can contact Leela on

Closing thought: What does Soliris teach pharma about Highly Specialised Technology appraisal?