Rare diseases must be priority in NICE review of methodologies, say senior industry figures

LONDON, 28 Feb (APM) - Updating the assessment process for rare diseases treatments must be a priority for England's health technology assessment (HTA) body NICE as part of a review of its methodologies, according to senior industry figures.
Several senior players in UK pharma told APM in a series of recent interviews that gaining National Health Service (NHS) reimbursement for orphan drugs remains a major challenge in England and NICE's review offers a chance to address these issues.
Proposed changes resulting from the review will be announced this summer, followed by a six-week consultation period. Final changes will be announced at the end of the year and will be implemented in 2021 by NICE, which provides healthcare guidance for the NHS in England.

Managing uncertainty

Jonathan Randell, senior director, value and access, Biogen, UK and Ireland, said in an email interview one of the main challenges of the current NICE process is "the lack of recognition that medicines for rarer conditions are likely to be priced at a higher level than medicines for much more common conditions where the volume of usage is likely to be higher".
There is also the issue that medicines for rarer diseases are likely to have smaller patient populations in clinical trials, meaning there is more uncertainty in the longer-term clinical benefit, he said.
Ben Osborn, managing director of Pfizer's UK business agreed, saying in an email interview that NICE needs to consider is the potential absence of large-scale clinical trial data for drugs in less common conditions due to the lack of patients and severity of the conditions.
"We recognise that this can lead to uncertainties regarding the cost-effectiveness of a new medicine, but there is a real need and great opportunity to consider how the new NICE methods can allow for a more pragmatic approach, particularly as treatments become more and more targeted for smaller subtypes of disease."
He said NICE should work with other partners, such as NHS England, to utilise different types of non-traditional data generated from outside of a clinical trial setting in order to support these types of product.
The issue is a pressing one for Pfizer as it is investing in several rare diseases areas, including a potential gene therapy for haemophilia A.
Biogen's Randell discussed what improvements he would like to see: "In order to increase access for patients it is important that medicines for rare diseases are given more flexibility when evaluating their cost-effectiveness, at present they are expected to achieve the same level of cost effectiveness as medicines for much more common conditions."
He suggested this could be achieved by the use of a "multiplication multiplier" that would adjust the approval threshold dependent on the size of the patient population to be treated i.e. the smaller the patient population, the higher the cost-effective threshold

Highly specialised technologies

NICE does have a specific process for some drugs for very rare diseases, known as highly specialised technology (HST) appraisal process which launched in 2013 and was updated in 2017 (APMHE 52246).
Drugs reviewed as part of the HST programme are assessed against a maximum threshold of £100,000 to £300,000 per quality-adjusted life year (QALY) rather than the standard £30,000 to cater for the high prices of orphan products.
However, the HST process has restrictive equalisation criteria that means it only applies to a small number of orphan products for very rare diseases.
This was part of the problem for Biogen's drug for spinal muscular atrophy (SMA), Spinraza, according to the company. The drug was not deemed eligible for the HST process so was reviewed under the STA framework and was rejected. Biogen and NHS England eventually agreed an access deal but it meant patients went without access for months (APMHE 62984).
Randell told APM the number of medicines appraised by the HST process since its launch has remained broadly similar at about three per year despite the increase in the number of medicines being developed for rare diseases.
"If the NICE capacity to conduct HST was increased, then more medicines could be reviewed by this process," he said.
Dr Paul Catchpole, director of value and access policy at trade body the Association of the British Pharmaceutical Industry (ABPI), also commented on the HST programme, telling APM its current criteria are "ambiguous and restrictive"
"There is a significant 'gap' between the STA and HST programmes, in terms of the thresholds used to consider medicines to be cost-effective, the decision-making parameters and types of evidence considered," said Catchpole.
"This gap creates a significant challenge especially for rare disease medicines - most of which are routed to STA making it difficult to achieve positive recommendations for all eligible patients in line with the licence. The review must find a way to address this gap."
He added that NICE could go even further and the HST evaluation programme criteria can be expanded and flexibilities can be applied in STA methods.


Both Randell and Osborn also discussed the prospect of NICE creating 'modifiers' for rare diseases.
These are factors, such as whether a drug is for end-of-life treatment, that are used to help decide whether to recommend a technology with an incremental cost effectiveness ratio above £20,000 per QALY.
Speaking at a conference earlier this year, Helen Knight, programme director for technology appraisal and highly specialised technologies (HSTs) at NICE, said is considering whether to create other modifiers, such as the rarity of a condition or whether it is for use in children (APMHE 65785).
Osborn said such a modifier could enable patients with rare diseases to be able to access medicines more quickly.
Randell also called for modifiers for rarity and disease severity, but also suggested there are other things that could be adjusted in the NICE process that would help increase access to innovative medicines.
These include amending the rate at the benefit of a medicine is discounted to take into account that many medicines produce benefits over the long term.

Conditional approvals

Randell also said Biogen believed greater use of conditional approvals or managed access agreements "would be useful" to improve access for orphan drugs, as has been seen in Scotland, which has specific manged access fund for orphan drugs (APMHE 58226).
"Under this approach, for a designated time period, patients would be given access to the medicine and real-world clinical outcome data is collected which is then used in the assessment of the medicine at the end of the agreement period," said Randell.
"This would help address the additional uncertainty that is often seen in clinical trials with medicines for rare diseases arising from the fact that the patient numbers in the rare disease trials are often smaller."
There is already a similar programme in place in England for cancer drugs known as the Cancer Drugs Fund. This is set to be expanded to other therapy areas under plans announced by the Conservative government (APMHE 65770).



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