NICE backs full NHS funding for Alexion's Soliris
UK health watchdog NICE has given its blessing to NHS funding for Alexion's Soliris, a treatment for an ultra-rare genetic disorder, which is said to be the most expensive drug in the world. The decision marks the first time that it has evaluated a rare disease ultra-orphan drug.
More than three years since Soliris (eculizumab) was approved to treat atypical haemolytic uraemic syndrome (aHUS), NICE has concluded that its £327,000-a-year price tag is justified by its clear clinical benefits for the 200-or-so patients with the disease in the UK.
The final draft guidance - published this week - looks likely to secure life-long access to Soliris, which is the first and only approved treatment for aHUS, although NICE stressed it has not yet delivered final guidance to the NHS and said "these decisions may change after consultation".
Final guidance on the use of eculizumab to treat aHUS is expected in January 2015, it said, and in the meantime interim funding for treatment with the drug will continue.
"We're very pleased to have the recommendation for funding on the NHS," Jon Beauchamp, aHUS business unit leader at Alexion, told pharmaphorum. "NICE has recognised the clinical value of Soliris throughout the process," he added.
aHUS is caused by chronic, uncontrolled activation of complement, a part of the body's natural immune system, which leads to the formation of blood clots in small blood vessels throughout the body. In turn, these clots can lead to stroke, heart attack, kidney failure and death. Within just one year of diagnosis, more than half of all aHUS patients will die, require kidney dialysis or suffer permanent renal damage.
"Eculizumab offers people with aHUS the possibility of avoiding end-stage renal failure, dialysis and kidney transplantation, as well as other organ damage," said NICE Chief Executive Sir Andrew Dillon.
Given Soliris' eye-watering price, the green light for funding comes with four conditions, largely unchanged from those laid out when the draft NICE recommendation was first published in September.
Use of the drug should be coordinated through an expert centre, and monitoring systems should be put in place to record the number of people with a diagnosis of aHUS as well as those who receive eculizumab, along with the dose and duration of treatment.
Alexion is funding a global aHUS registry to monitor patients who receive eculizumab, as well as those not on treatment, and physicians from the national coordinating centre have access to that data, said Beauchamp.
Withdrawing therapy
The monitoring requirement also ties in with NICE's third requirement, which is to establish a 'protocol' for starting and stopping Soliris therapy in a bid to make sure the drug is used only as much as needed.
Given that the approved label for the drug specifies lifelong therapy, this was the source of considerable contention when the draft appraisal was first published. Alexion argues that complications, including graft failure needing haemodialysis, renal insufficiency, end-stage renal failure and respiratory distress needing intubation, have all been reported after stopping the drug.
"We believe that any clinical decision to stop would be one that the treatment clinician should make in consultation with the patient, rather than being mandated through a protocol," said Beauchamp, who noted that the licence indicates withdrawal could take place because of an adverse reaction, for example, or the development of neutralising antibodies in the patient that would limit its effectiveness, although this has not been encountered to date.
"NICE says clearly in the FED [final evaluation determination] that the intention is to try to lower the budget - we would contend that there is clinical data showing that if you stop treatment, patients may be put at risk."
Dillon said that, given the high cost of the drug, the Highly Specialised Technology (HST) committee "felt that the budget impact of eculizumab would be lower if the potential for dose adjustment and stopping treatment was explored."
During the consultation process, scenarios which might allow withdrawal of therapy were discussed, including, for example, in a dialysed patient who remains on dialysis after several months of eculizumab treatment, said Beauchamp.
"We would argue that this is a systemic disease and, while you do get remarkable improvement in kidney function in some patients, this will not happen in cases where the kidney is severely damaged.
"I don't think there are obvious categories that can be put in a protocol for stopping therapy - this needs to be considered on a case-by-case basis."
The final requirement is for a research programme - that would be carried out by NHS organisations - to evaluate when stopping treatment or dose adjustment might occur. Alexion will not be directly involved in that research but would make its registry data - from around 600 aHUS patients - available for the project.
"NICE has estimated a first-year budget impact of a little under £58 million, rising to £82 million after five years, although Alexion maintains this is an over-estimate"
NICE has estimated a first-year budget impact of a little under £58 million, rising to £82 million after five years, although Alexion maintains this is an over-estimate because it assumes all patients would be treated on day one and would all be adults; it claims around 40 per cent are children receiving a lower, cheaper dose.
First test of HST process
The verdict on Soliris also completes the first assessment by NICE under its new HST appraisal process, which recognises that the agency's standard approach to determining the cost-effectiveness of drugs cannot realistically be applied to "highly specialised technologies which may benefit people with very rare diseases at a high price".
Rather than relying on NICE's standard QALY (quality-adjusted life year) measure, the HST takes into account the low number of patients involved and a silo budgeting approach.
On balance, Beauchamp believes the HST procedure worked fairly well for eculizumab and it is "positive" that a mechanism exists with different criteria to assess treatments for rare diseases.
"It evolved as we were going through it, and now there is more certainty about the process," he said. Alexion was asked to justify the price of its drug earlier this year and - aside from believing that was outside NICE's remit - the company would have liked more clarity on the information it was expected to produce at the outset as this would have helped speed up the review process.
"We are pleased that through all the iterations and considerations - in what is a very thorough process - NICE has concluded it is an appropriate use of NHS resources."
Alexion is in the throes of sending another product for an ultra-rare disease - asfotase alfa for the genetic disorder hypophosphatasia (HPP) - through the HST process, but at the moment it is unclear whether this will follow the same path as for eculizumab, such as including a request for R&D cost information to justify price.
"I don't know what the next process will look like, but the outline is there and we believe it should go smoothly, with the information to be requested absolutely clear at the outset," said Beauchamp.
Interim funding for eculizumab was originally backed by the Advisory Group for National Specialised Services (AGNSS), which was dissolved last year and its responsibilities transferred to NICE.
The money for the drug comes out of NHS England's specialist commissioning budget, although this is being placed under increasing pressure by the cost of providing medicines under the Cancer Drugs Fund and - with the NHS already grappling with a significant overspend - there are real concerns about how future rare disease therapies will be funded, both during and after the reimbursement review process.
NICE acknowledges that in a statement, saying that "NHS England and [Alexion] should consider what opportunities might exist to reduce the cost of eculizumab," without providing any further detail.
Beauchamp said that, despite fears that expensive, orphan treatment will bankrupt healthcare systems, "there is quite good evidence to suggest this will not happen and costs will plateau".
"I don't think treatments for ultra-rare diseases are going to suddenly snowball and overwhelm the NHS," he added.
"When we look at the UK, there is really no better mechanism for existing products that the Pharmaceutical Price Regulation Scheme (PPRS) as this gives the government "certainty that the approximately £8 billion spent on that band of branded medicines will increase very little over the next five years."
The PPRS "guarantees that any new patient with aHUS that starts treatment this year or next will be at net zero cost to the NHS, with only a small allowable growth in the following three years".
The latest verdict on eculizumab was also welcomed by aHUSUK, a support group for patients with the disease and their families.
"Of course we are delighted for every sufferer of aHUS and their families," said aHUSUK chairperson Emma Woodward.
"But we also recognise something very important has just occurred - this is the first time NICE has evaluated a rare disease ultra-orphan drug."
"We are impressed with the committee's approach and believe that NICE has demonstrated a vision, willingness and capability to devise a process for evaluation of other such complex technologies to address the needs of those who seek equity of access to treatments of their severe rare diseases," she added.
About the author:
pharmaphorum's staff reporter has many years of experience writing on pharma and health topics.
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