Parents of young boys with Duchene muscular dystrophy must be pretty resilient. But the fact that the two different medicines assessment bodies for Scotland and England gave two different verdicts about the same drug in the same week will have tried the patience of even the toughest of them.

On Monday 11 April, the Scottish Medicines Consortium (SMC) announced that it was not recommending a medicine called Translarna for use in NHSScotland to treat boys who are aged five years and over, who are still able to walk and whose Duchenne is caused by a nonsense gene mutation.

Four days later, on Friday 15 April, The National Institute for Health and Care Excellence (NICE) recommended Translarna should be funded for use in England.

The NICE decision is based on a Managed Access Agreement under the organisation’s Highly Specialised Technologies Programme, which the charity Muscular Dystrophy UK said, in a statement, now needs to be implemented by NHS England.

“We’re pleased that the Managed Access Agreement – which we called for last year and have worked to help develop – has led to the approval of the drug.

“A Managed Access Agreement is when a drug is made available for a limited period of time (in this case for 5 years) often at a discounted price, to allow further evidence to be gathered on its use whilst also ensuring that patients receive access to the drug.”

But for those affected in Scotland, the SMC decision closes the door on Translarna being routinely available and, as yet, no alternative door has been opened.

The Scottish NHS does not have an equivalent of the Highly Specialised Technologies Programme or Managed Access Agreements, instead relying on companies to offer a discount that may or may not be accepted.

Robert Meadowcroft, Chief Executive of Muscular Dystrophy UK, said he was bitterly disappointed by SMC’s decision to refuse a medicine that he says could transform the lives of those affected:

“Translarna could give eligible boys precious time to be able to walk for longer, helping to delay the progression of the condition. For a young person with a shorter life-expectancy, facing the acute psychological, physical and practical challenges of a progressive condition, this is of immeasurable value. It is now left to parents, in a postcode lottery, to approach their regional NHS board, in the hope funding for this drug can be agreed for their child. We will continue to fight with the families.

“We are now calling on Translarna’s producers to negotiate a sustainable price and to work with the SMC towards a solution, to ensure Scottish families don’t miss out on a drug that could transform lives. No one should ever underestimate that Duchenne muscular dystrophy is a devastating condition, and we should take every opportunity to slow or halt the condition while we search for a cure.”[i]

Since 2012, the SNP Scottish Government and the Scottish Parliament’s Health and Sport Committee have sought to improve access for patients to medicines for people with end of life and very rare conditions. An additional Patient and Clinical Engagement (PACE) meeting and report stage has been added to the consideration of such medicines by SMC, while NHS Boards were also told to accept more Individual Patient Treatment Requests.

Translarna was considered under the PACE process but the answer was still no. SMC’s verdict was that Translarna was too expensive:

“The submitting company’s justification of the treatment’s cost in relation to its health benefits was not sufficient and in addition the company did not present a sufficiently robust economic analysis to gain acceptance by SMC.” [ii]

Translarna is one of three medicines that SMC has now turned down for Scotland that have, soon thereafter, been given the green light for patients in England by NICE.

Vimizim, for the rare inherited disease Morquio A syndrome, affecting nine people in Scotland, was turned down in September 2015 by SMC and then accepted by NICE in December.

Soliris, for atypical haemolytic uraemic syndrome – a very rare life-threatening condition that affects less than 2 people per million – was not recommended by SMC in January of this year and accepted eight days later by NICE. Both medicines had been considered by SMC under the PACE system.

Without discount, Vimizim is said to cost £395,000 per patient per year[iii] while Soliris is reported to cost £340,000 per patient per year[iv]. 

Giving evidence last month to the Health and Sport Committee[v] SMC’s chairman Professor Jonathan Fox said:

“Access to new medicines cannot come at any price. That has been stated many times, even by patient groups. We have, very deliberately, increased flexibility following the committee’s advice and the cabinet secretary’s instruction a few years ago, and there is no question but that that has increased access to these medicines. In addition, we have downgraded the importance of the cost-effectiveness information for ultra-orphan medicines. However, overall cost effectiveness—value for money—must still play some part in drug decision making.”

The question that now arises is whether SMC can continue with one approach to these high cost, small population medicines that leads to their being refused while NICE is now employing a different approach that reaches a different conclusion? If NICE has adopted a new system for these medicines, can SMC justify sticking with an approach which, at its core, remains unchanged from the day it began?

In its excellent Patient Charter, Patient perspectives and priorities on access to medicines for rare conditions in Scotland (published this week[vi]) Genetic Alliance UK comments on the Quality Adjusted Life Year (QALY) effectiveness measure currently used by SMC:

“While QALYs can provide a useful indicator of an individual’s anticipated health gain following a medical intervention, they do not fully capture the benefit a treatment can offer to patients and families, particularly if they are affected by a rare condition. This remains the case even with the use of modifiers.

“Therefore, it is clear that the health economist’s tool box needs updating so that funding bodies can make decisions that enable patients with rare conditions to access new treatments, in line with public and government opinion and the equity standards required of NHS Scotland under anti-discrimination legislation.”

This is no doubt something that Dr Brian Montgomery, who is reviewing the workings of SMC for the Scottish Government, will address.

Ultimately, perhaps, this about whether government – or society – is willing to pay for the sorts of medicines that were only imagined when SMC began its work in 2002.

In the meantime, what comfort can be offered to the parents of boys with Duchenne muscular dystrophy?

The pharmaceutical industry journal Pharma Times says that Translarna costs £222,000 per patient per year before any discount[vii]. It is predicted that five patients in Scotland would be appropriate for Translarna immediately, rising to six in year five. At full price – the actual discounted cost to the NHS would be less – this equates to £1.11 million in year one.

There are some parallels with the medicine Kalydeco for the treatment of cystic fibrosis. Despite two submissions to SMC, Kalydeco is not recommended for use in NHSScotland “because the balance of costs and benefits meant that it was not considered value for money”[viii]. Kalydeco was accepted for use by England’s four NHS Specialised Commissioning Groups in 2012.

Young cystic fibrosis patients in Scotland with the G551D mutation are, however, receiving Kalydeco following a Group Patient Treatment Request, funded by the Scottish New Medicines Fund [see my commentary on the fund[ix]].

There is at least £90 million pounds in the New Medicines Fund this financial year.

Given the precedent set by Kalydeco, it is reasonable to expect clinicians to submit a Group Patient Treatment Request asking that Translarna be funded for the half dozen boys appropriate for it. In which case we would have another instance where SMC has said no to a medicine and every suitable patient will still get it.

Coincidentally, Kalydeco was discussed again at the last SMC meeting. It had been submitted for consideration for the treatment of cystic fibrosis caused by a much broader range of gene mutations than just G551D. The decision is due to be published on the first Monday after the Scottish election.

[i] Muscular Dystrophy UK News Release: http://bit.ly/23x0Jsn

[ii] SMC Advice: http://bit.ly/1rBkj9w  

[iii] Pharma Times http://bit.ly/1SRHmbP

[iv] Pharma Times Report http://bit.ly/1YV3MXZ

[v] Health and Sport Committee Official Report 1 March: http://bit.ly/244Zi8i

[vi] Genetic Alliance UK: http://bit.ly/1SukcGo

[vii] Pharma Times online http://bit.ly/1Tfu2s3

[viii] SMC Briefing Note: http://bit.ly/1qWDnOy

[ix] Ettrickburn commentary 14 April http://www.ettrickburn.com/default.asp?page=commentary&article=1