Soliris, the world’s most expensive drug: will NICE judge it affordable?

NICE and Alexion not budging on Soliris price - patient groups speak out in advance of ruling - decision will set precedent for rare diseases.

NICE is on a collision course with a pharma company once again – this time over Soliris, the most expensive drug in the world.

Approved in 2011 as the first and only treatment for the very rare, life-threatening blood disorder atypical haemolytic uremic syndrome (aHUS), Soliris has transformed the lives of sufferers, turning it from a potential killer into a chronic but manageable condition.

However this transformational effect comes with a huge price tag - £340,200 per adult patient per year, according to NICE's estimates.

England's healthcare cost effectiveness watchdog agrees with pharma company Alexion that Soliris (ecluzimab) is very effective in treating patients with aHUS, which causes blood clots in small blood vessels in the body, leading to kidney failure and the need for dialysis or kidney transplants.

The disease affects just 200-or-so patients in England, and yet there are concerns about it consuming a disproportionately large part of the budget - NICE estimates it would cost the NHS about £58 million in the first year, rising to over £80 million in the fifth year.

NICE is concerned that Soliris, and a wave of new and very high-cost treatments for rare diseases will cause a crisis in the NHS budget in England, which is already in overspend. In March this year, NICE issued a preliminary appraisal that the drug was clinically effective, but refused to recommend its use on the NHS without Alexion first providing further justification of its high price.

Significantly, it also asked the budget holder, NHS England for clarification on how it decides funding for specialised treatments - underlining the fact that finding ways to pay for new, very high cost treatments for rare diseases is a conundrum for everybody involved.

"Patient group AHUSUK disputes NICE's estimate of £340,200 per patient per year – which would make the UK price higher than in the US"

After further discussions, NICE is at last expected to make its final ruling next month. A decision on Soliris has been pending on the drug for three years, characterised by repeated delays, disagreement and confusion about the process. But unlike other recent decisions – such as Roche's breast cancer treatment Kadcyla – outright rejection is not an option with Soliris. That's because it is a life-transforming and life-saving drug, and also because an 'interim' arrangement to make it available to all eligible patients has been in place since 2013.

That means putting pressure on Alexion to offer price cuts - or find other ways to trim costs - look like the only realistic options for NICE.

But just as Roche said NICE's rejection of Kadcyla showed the UK's health technology assessment (HTA) system was 'broken', healthcare payers are equally warning that so many new high cost treatments are simply not affordable.

Soliris has a US price of $536,629 (according to analysts EP Vantage) per patient per year, making it the most expensive prescription drug on the US market, well known as being the highest cost market in the world. However NICE is publicly quoting a cost of £340,200 ( more than $571,000) per adult patient per year – which (at current exchange rates) would make the UK price even higher than in the US.

However, neither the US or UK official 'list' prices are accurate reflections of the price actually paid by the health systems, as pharma provides heavy – but confidential - discounts in both countries.

Patient groups and Alexion also dispute NICE's calculation of the overall cost of the drug, and say it hasn't factored in enough of the savings the drug will produce, by reducing the serious complications which arise from long-term dialysis, for example. On the other hand, Alexion has insisted on confidentiality agreements to keep Soliris' price out of the public domain, and NICE has criticised Alexion for refusing to disclose the overall cost of its drug.

Setting a precedent for rare diseases

But whatever the actual price Alexion is proposing for use on the NHS, it is clear this extremely expensive but highly effective medicine will put huge pressure on NHS budgets. Not only that, Soliris is the first appraisal by NICE's Highly Specialised Technology (HST) Evaluation Committee, and will therefore set a precedent.

While NICE and Alexion are remaining tight-lipped, patient groups involved in the drawn-out appraisal are speaking up, and calling for an agreement to be finally thrashed out.

Len Woodward is a founding trustee of AHUSUK, a support group for patients with the disease and their families. He is an expert patient witness for the Soliris appraisal, and has been involved in the process from the outset.

He is sympathetic towards the committee charged with creating a fair appraisal process in this specialised area, saying:

"I have no doubt they are really trying to produce an ultra-orphan drug appraisal process," but adds that it is clear NICE has not yet settled on a clear methodology for assessing such drugs.

NICE is not using its well-established cost effectiveness methodology the QALY (Quality-adjusted life year, an approach which has its supporters and detractors). Instead, it is developing a specific methodology for ultra-orphan drugs which assesses their value compared to existing treatments, and also calculates what existing treatments elsewhere in the system might get squeezed out because of a finite budget – the so-called 'opportunity cost'.

Len Woodward says despite its good intentions, NICE has gone round in circles when considering the economic case for Soliris, and hasn't yet defined how 'cost effectiveness' might be different from other terms such as 'affordability' or 'value for money'.

The methods NICE settles on and the final outcome of the Soliris decision could have major implications; not just in the UK, but for health systems, the pharma industry and rare disease patients around the world, as NICE decisions are closely followed and emulated by other countries.

NICE and Alexion not backing down

The Soliris appraisal has largely been conducted via complex health economic arguments and counter arguments, but NICE's HST committee and representatives came face-to-face on 24 July in Manchester in a public meeting. Exchanges between Alexion and the committee – one side emphasising the drug's clinical value – the other its expense – became heated, and by all accounts neither showed a willingness to back down.

Alastair Kent is chair of the Rare Disease UK, one of the most influential organisations promoting the interest of patients with rare diseases.

He says the Manchester meeting was a 'robust discussion': "It was a fascinating example of both sides 'playing chicken,' NICE and Alexion both hoping the other would concede ground.

"Everybody agrees it is a game changing therapy – all the conversation was about the price" - Alastair Kent

The 'interim' arrangements to fund treatment for all eligible patients makes it almost inconceivable that NICE would reject Soliris after all this time, and put aHUS patients' lives at risk. This also puts NICE and NHS England – which pays for the drug in England - in a weak position when applying pressure on Alexion to cut its prices.

Alastair Kent acknowledges that the NHS is facing a huge cost if it approves the drug, but says NICE and NHS England have little room for manoeuvre.

"If you are over a barrel, the thing to do is to stop struggling," he says.

He says the NHS and the UK government missed its chance to discuss the cost and justification for price several years ago, when AGNSS - the predecessor to NICE's HST committee – was reviewing Soliris. When AGNSS recommended Soliris but raised concerns about its price, the government simply scrapped the committee, and asked NICE's HST committee to start again from scratch. Then in March this year, the NICE committee ruled that Soliris was very clinically effective, but made the (virtually unprecedented) demand for detailed information about the R&D and manufacturing costs of the drug so it could understand why the drug carried such a high price.

While Alexion's response to this request has not been made public, it is highly unlikely this will yield any useful new information for NICE, and it is not even clear how such information could be considered within NICE's remit.

"The moment we start saying this is jolly expensive, we lose our independence"

Asked why patient groups such as his shouldn't get involved in direct discussions about price – including pressuring pharma companies to lower their prices - Alastair Kent said Rare Diseases UK needed to stay out of these talks.

"We don't get involved in discussing the price because the price is a commercial decision negotiated with the government; we get involved in the clinical value of the medicine."

He added: "The moment we start saying this is jolly expensive, we lose our independence."

Nevertheless, he does believe that significant cost savings could be made through a number of novel approaches.

Real World Data a possible solution?

One of the most promising new avenues is the use of Real World Data (RWD) – the collection of clinical outcomes data from patients taking the drug in the 'real world' as opposed to data amassed in the more artificial and time-limited scope of clinical trials.

Kent says there is lots of scope for gathering more health economic data on the drug at the same time as allowing access to it. In particular, he believes that fine-tuning the dose – so that patients receive enough to gain the maximum benefit, and no more – will help rein in costs.

"I would say there is scope for incorporating RWD into very expensive rare drug therapies. The drug was approved on far from complete data – there is scope for modifying the treatment regime in the light of experience."

Both Len Woodward and Alastair Kent say that criteria for stopping treatment with Soliris could also be agreed – either in cases where there is evidence that the drug is no longer working, or in some cases where patients could safety come off the drug with no ill-effect; but they say more research is needed into these and other aspects of treating the disease not currently well understood.

Confusion over funding and price negotiations

The row over Soliris is just part of a patchwork of policies on access to medicines in the UK, which has grown increasingly confusing in recent years.

Repeated rejections by NICE of expensive cancer drugs led to a dedicated £200 million annual Cancer Drugs Fund (CDF) in England in 2011, which effectively allows drugs to bypass NICE's cost-effectiveness test. Campaigners in other disease areas, including rare diseases, have complained at the unfairness of cancer drugs gaining a 'free pass' in this way.

In Scotland, the situation is reversed, there being no Cancer Drugs Fund, but one instead for rare diseases. Scotland's 21 million fund was set up in 2013 after cystic fibrosis drug Kalydeco (ivacaftor) was rejected by Scotland's NICE equivalent the SMC.

Neither of these funds addresses the long-term funding problem for high cost drugs, but both are also now going into overspend.

A brand new version of the PPRS, the UK's pricing system for medicines, was introduced in January this year and seemed to offer a great deal for the NHS and the taxpayer: the pharma industry has agreed to guarantee low growth in the total medicines budget, and any health service spending above this level will be paid back by pharma. This means, in principle, that the UK pharma industry is underwriting the NHS drugs bill – and yet no part of the NHS seems to be taking this agreement seriously and, if anything, has become more focused on controlling costs.

Finally, for NICE and Alexion, the appraisal process is clumsy and puts lots of obstacles in the way of direct negotiation on price and access, which would have to be conducted between the company and the Department of Health.

Alastair Kent says his organisation has asked for extensive changes to how NICE operates in the long term, but wants to see a decision finally made on Soliris.

"It would be ridiculous if it drags on any longer. There is nothing more than can be said [between Alexion and NICE] in a formal context.

"I think if it goes on any longer, the aHUS patients will have grounds for calling it maladministration. If they can't get this one right, it doesn't bode well for coping with the challenge of more rare disease treatments – there are lots more in the pipeline."

NICE is unlikely to find a last-minute perfect solution to its dilemma within the next few weeks: how to give access to a very effective new drug and yet control costs at the same time, and is likely to give a 'yes' to Soliris, albeit with conditions. Yet the new generation of high cost, targeted drugs will keep coming, meaning that a reckoning on budgets and affordability can only be delayed, not put off inevitably.

Link

NICE's Highly Specialised Technologies Guidance – interim methods and process

About the author:

Andrew McConaghie is pharmaphorum's Managing Editor, Feature Media. He has been writing about the pharmaceutical industry and NHS since 1999 and provides regular exclusive news and insights from the sector for pharmaphorum.

Andrew can be contacted via: andrew@pharmaphorum.com

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