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Health economic assessment of ultra-orphan medicine Soliris finally published

August 14, 2015

Earlier this year, the National Institute for Health and Care Excellence (NICE) published its recommendation on Soliris¹ (eculizumab, from Alexion), an ultra-orphan drug, that is the first medicine to be assessed under their new Highly Specialised Technologies (HST) program. The focus was on Soliris’ treatment for aHUS, a very rare, life-threatening condition. And the recommendation was a culmination of 7.5 years and complicated history.


Atypical haemolytic uremic syndrome (aHUS) causes blood clots to form in small blood vessels throughout the body. This can damage vital organs, such as the kidneys, brain and heart. Without Soliris, patients typically have plasma therapy and/or dialysis and/or kidney or kidney/liver transplants. Prognosis is poor. Most patients are identified during childhood, and many do not live to adulthood. Currently, there are an estimated 140 to 200 aHUS patients in the UK.

Soliris typically costs around £340,000 for the first year of treatment of aHUS and £327,000 per year thereafter. According to the Summary of Product Characteristics, treatment is for life. Evidence to date suggests that with Soliris patients may live a near-normal lifespan.

Soliris for aHUS treatment

Historically, NICE did not assess ultra-orphan diseases, which were commissioned centrally by the NHS. In the mid-2000s the Advisory Group on National Specialised Services (AGNSS) was established to assess and make recommendations on these drugs. AGNSS used different assessment criteria, and placed much less weight on cost per quality-adjusted life year (QALY) than NICE. After some delay Soliris was referred to AGNSS for assessment. In 2012 AGNSS recommended that Soliris be funded by the NHS in England, but ministers were worried about the budgetary impact. Rather than accept the recommendation, they referred Soliris to NICE for further assessment. At the same time, AGNSS was folded into NICE to become the HST program.

In the meantime, in 2013 NHS England established an interim specialized commissioning program for Soliris for some patients. This was in response to pressure (not least from the House of Commons) that patients were dying for lack of access to treatment. It is believed that about 70 patients are currently being treated.

The Soliris guidance is the first to emerge from their HST program – a mere seven and a half years after it was first licensed. Such is the power of bureaucratic delay!

Committee’s key points of guidance

Eculizumab, within its marketing authorization, is recommended for funding for aHUS only if all the following arrangements are in place:

  • coordination of eculizumab use through an expert centre
  • monitoring systems to record the number of people with a diagnosis of aHUS, and the number who have eculizumab, and the dose and duration of treatment
  • a national protocol for starting and stopping eculizumab for clinical reasons
  • a research program with robust methods to evaluate when stopping treatment or dose adjustment might occur.

This is not as onerous as it might sound, since all the elements except the research program are already in place. NHS England was actively involved in the process and has said that “it is able to meet all the conditions for reimbursement except for the research program, which will require longer to establish.”

The Assessment Committee accepted that “eculizumab represents a step change in the treatment of patients with aHUS and could be considered a significant innovation for a disease with a high unmet clinical need.” They took this view despite the “limitations in the evidence base, particularly because of the lack of randomized trial evidence.” Evidence came from Phase 2 trials – the largest including 41 patients, and in total 100 patients – and a retrospective observational study of 30 patients.

What clearly swayed their decision was the evidence from clinical experts and patients and their representatives, who were strongly in favor and stressed the lack of alternative therapies – hence the “step-change” conclusion. The contribution of a well-organized patient interest group and strong clinical support is clear.

While the company and the Evidence Review Group both calculated cost-effectiveness, this information has not been published, since the company deems it to be confidential. Substantial QALY gains are recognized, but there are no cost-per-QALY figures, and any figures would clearly be beyond anything NICE would normally accept.

Budget impact clearly was a key factor in the decision

While estimates varied, the expectation was that the cost to the NHS in England would be in the range of £68m (patient organization’s estimate) to £82m (Evidence Review Group’s estimate) in year five. The company also produced a (presumably lower) estimate but would not allow its publication. To put this into context, NHS England spent £156m on high-cost drugs under the specialized commissioning program in 2013/4, and highlighted that a potential 50% increase in this figure could only mean withdrawing funds elsewhere, in the context of flat-funding plans for the NHS overall. Finding ways to minimize budget impact is clearly behind the recommendations on starting and stopping rules and research on the potential to adjust (i.e. reduce) doses.

Assessing the cost

It is clear that the committee reached this recommendation despite its exasperation with Alexion. Comments appear throughout the document about information redacted as commercially confidential. Though Alexion clearly challenged the committee’s decision to assess affordability, the committee robustly defends its position.

Wales and Scotland are not included in the HST recommendation which apply to England only

It should be noted that this recommendation applies only to England. Alexion declined to submit to both the Scottish Medicines Consortium and the All-Wales Medicines Strategy Group, and in both territories Soliris is “not recommended”. According to the patient group, two patients in Scotland are being treated under Individual Patient Treatment Requests, but this is a bureaucratic and uncertain procedure.

For further information or advice, please contact Tim Fitzgerald or Jim Furniss.



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