Cancer is a highly emotional subject and one that creates fear among the general public, given the fact that it can be often be fatal, undetected and affect young and old alike.
The cure for this fear has become the cancer drug that, through exposure in the national media, has become a ‘miracle cure’ in the popular imagination, and is seen as the closest thing to an elixir in the modern world.
But in England, the question of access to these medicines has for more than 15 years been answered by NICE – a body that regularly denies new oncology products on the NHS given their high costs, and relative low efficacy.
In a bid to improve access a specialist, silo budget – the Cancer Drugs Fund (CDF) – was established. Since March 2011 the CDF has injected an extra £200m a year into the NHS and was initially meant to be a stop-gap before a new drug pricing scheme, known as value-based pricing (VBP), would overcome the market access problems that saw NICE reject so many of these drugs.
VBP died a long, slow death in 2013 however and was replaced with a similar system to that used for over 50 years in the UK, meaning no change to market access for cancer drugs would be forthcoming.
Realising defeat, the government announced in September last year that it would increase the annual fund by an extra £80m per year, bringing it to £280m.
But all was not what it seemed – the reason this was done was not because it wanted to fund more medicines, but because the CDF was expected to overspend its current budget by around £80m given that more patients wanted to use the Fund, and that the cost of oncology products had risen above inflation year-on-year.
Things seemed even bleaker when NHS England, which is responsible for CDF, then said it would have to increase this still further, to around £340m in the coming year, but also needs to re-assess dozens of these medicines, and remove those that were forcing the Fund to haemorrhage so much money.
After a three-month consultation, NHS England announced last month it had decided to cull 16 drugs that cover 25 indications in cancer, a process known as ‘de-listing’.
The vast majority of these medicines are for colorectal, breast and blood cancers (see table 1 for the full list), although both NICE and the CDF do recommend a number of alternative personalised medicines for all of these diseases, as well as chemotherapy agents.
On top of this however three treatments have been added to the list for later this year, namely: Amgen’s Vectibix (panitumumab) for bowel cancer and Janssen’s Imbruvica (ibrutinib) for Mantle cell lymphoma (a type of non-Hodgkin lymphoma) and chronic lymphocytic leukaemia.
‘Shocked, disappointed and appalled’
But the decision to ‘de-list’ has caused anger and outrage among the industry and cancer charities that have denounced the ‘arbitrary’ nature of these cuts, and called for a major reform into how these medicines are paid for in the NHS.
One of these has been Sanofi, whose prostate cancer drug Jevtana (cabazitaxel) and bowel cancer medicine Zaltrap (aflibercept) were deemed too expensive for both the specialist CDF and for NICE.
Both industry and the NHS bear some responsibility for this situation – Roche
Tarja Stenvall, general manager of Sanofi in the UK, tells PME: “We are hugely shocked and disappointed at this decision against Jevtana. We will do everything in our power to appeal this decision and are willing to hold open discussions to find a way forward so that patients still have access to this important medicine.”
This echoes much of the tone coming from pharma. Using very strong language for the normally conservative industry, Eisai said it was ‘appalled’ at the decision to cut its breast cancer drug Halaven (eribulin).
The biggest beneficiary of the CDF in financial terms has been Roche, given that it specialises in cancer drugs, but has had many rejected by NICE over the years.
The Swiss firm has, in relative terms at least, not come out too badly during the de-listing process as two of its newer cancer medicines, namely breast cancer treatments Perjeta (pertuzumab) and Kadcyla (trastuzumab/emtansine) – the latter the most expensive cancer treatment in England at £90,000 – being kept on the list.
But its flagship cancer drug Avastin (bevacizumab) – the biggest selling oncology treatment in the world with five main cancer licences in the EU – has seen three indications removed, although five still remain available for funding.
The Swiss firm’s UK subsidiary told PME that: “The CDF was only ever meant to be an interim solution. We are now seeing the first casualties of a failure to reform the wider system of access for established cancer medicines. Treatments such as Avastin, which is the standard of care for many cancers, are being taken away from some patients.”
The company’s spokesman said the fact that some effective medicines are being removed from the CDF “is a symptom of a wider problem – the failure to reform pricing and reimbursement systems”.
He went on: “It is deeply worrying that some established treatments that form the standard of care for cancer are being removed from the CDF without any alternative commissioning.
“Both industry and the NHS bear some responsibility for the situation and both have a part to play in addressing it. We stand ready to work with others so that patients are not disadvantaged.”
Two-tiered system
Eli Lilly said it disagrees completely that the “CDF Panel should introduce cost in their decision-making criteria”.
A spokesman for the company’s UK subsidiary told PME: “NICE already performs robust cost-effectiveness analysis and any replication of this will create a two-tiered system based on arbitrary thresholds that threaten to undermine the work of NICE.”
The firm also pointed out the inherent unfairness of a system that favours cancer over other disorders and diseases, saying: “The government must consider the need to improve access to medicines for the many other diseases that do not have a specific access scheme, such as dementia or multiple sclerosis.”
GlaxoSmithKline has been the hardest hit in terms of drugs, given that three of its treatments: breast cancer medicine Tyverb (lapatinib), leukaemia drug Arzerra (ofatumumab) and non-adipocytic soft tissue sarcoma treatment Votrient (pazopanib) have been cut.
Unlike most of the other companies affected, the London-based firm did not however seek to comment on the loss of its drugs from the Fund.
Meanwhile, shortly after the de-listing announcement, the Anglo-Swedish firm AstraZeneca said it would not even bother putting its newly approved ovarian cancer drug Lynparza (olaparib) up for funding via the CDF, citing “concerns by a number of limitations within the recent re-review process, which has been geared more towards the assessment of those medicines previously on the CDF list than newly-approved medicines like Lynparza”.
‘Bad news’ for patients
It should be noted that those drugs that have been cut can still be used by patients who have been prescribed them for as long as they need them, and the new rules do not come into place until 12 March of this year.
But charities have acted just as angrily as pharma, with those representing bowel cancer and breast cancer patients pouring particular scorn on both NHS England and the de-listing process.
Mark Flannagan, chief executive of the charity Beating Bowel Cancer, tells PME that this is all simply “bad news for bowel cancer patients”.
He estimates that as much as 65% of patients with advanced bowel cancer “face the probability of an earlier death by being refused innovative treatments that were available before [from the CDF]”.
He went on: “If the Cancer Drugs Fund was meant to be a sticking plaster, now it has been ripped off for advanced bowel cancer patients and what we have left is an open wound.
“This isn’t a done deal – we need a long term sustainable solution that benefits patients. NHS England and the drug companies need to get round the table and agree a solution. We haven’t given up on bowel cancer patients and nor should they.”
Chief executive of the Myeloma UK charity Eric Low OBE has long been a critic of the CDF. He said that of course he was disappointed that a myeloma licence from Takeda’s Velcade (bortezomib) had been de-listed, but added that there were larger problems at hand.
He explained: “Quick-fix measures such as the Cancer Drugs Fund are not effective long-term solutions to securing cancer patients access to medicines. Throwing money at fixing a complex issue does not solve the underlying reasons why these drugs are not available on the NHS in the first place.
“As a number of high profile cancer drugs have been identified for being ‘de-listed’, there has been public outcry in the press and media from a number of sources, including patient organisations and industry.
“We totally understand why stakeholders including charities and industry are upset by the removal of certain treatments from the list, but it should not have come as such a surprise.
“This situation has been inevitable since the establishment of the Fund, given the finite and fixed nature of the budget and the insistence of certain pharmaceutical companies to price their treatments at a level that does not represent an appropriate level of value to the NHS.”
In a statement to PME Mia Rosenblatt, head of policy and campaigns at Breast Cancer Campaign, said that it was disappointed that licences from three breast cancer drugs: Eisai’s Halaven (eribulin), GSK’s Tyverb (lapatinib) and Novartis’ Afinitor (everolimus)), were to be de-listed.
She said: “Halaven has to date received more applications for use than any other breast cancer drug on the list. Its removal could have a considerable impact on the lives of around 800 women who access the drug each year.
“With breast cancer drug after breast cancer drug rejected since the introduction of the Cancer Drugs Fund, the Fund has proved a lifeline for thousands of people with breast cancer.
“However, the announcement has put into sharp focus the need for a long term sustainable solution for access to cancer treatments. We do not want to see people locked out of treatment options that could significantly improve their quality and length of life.”
We will do everything in our power to appeal [the Jevtana] decision – Sanofi
Systemic issue
But is continuing the CDF the right way forward, or is it papering over the cracks inherent in both the market access process in England and the misalignment between pharma’s pricing and the efficacy of their medicines?
In terms of access, the Fund has been a great success. There have been around 55,000 cancer patients in England that have gained access to new oncology medicines as a result of the Fund who otherwise would not have been able to (or would have had to wait longer for the treatment).
But there is no central database to prove either way whether these patients have survived longer as a result of taking these medicines, or whether they were a cost-effective intervention. Given that many of these medicines were deemed too costly for the NHS by NICE, it is reasonable to expect it hasn’t been.
The Fund has been a political intervention, the personal policy of the British Conservative Prime Minister David Cameron, and aimed at nullifying negative NICE decisions and appeasing angry newspaper editorials about ‘nasty NICE’ rationing cancer care.
Curiously, the announcement of the CDF de-listing process was met with silence from the Prime Minister; it is uncertain how much he was briefed on the decision to cut the 16 drugs.
As has been seen, pharma is not a major fan of the Fund as a long-term solution because it simply does not address the problems of low access, which predominately come from NICE’s negative decisions.
The ABPI tells PME that it wants a root and branch political reform of NICE, and is disappointed that the recent internal review by NICE’s board into its practices has not yielded any real change in how it assesses medicines.
Its director of value and access, Paul Catchpole, told PME: “To ensure that all patients get access to the best new medicines we are calling for reform of NICE to enable it to look at new medicines more rapidly and with greater flexibility whilst also balancing the affordability issue. The long-term sustainable solution is of course to utilise the expertise of NICE alongside that of NHS England to address this challenge.”
NICE is now in fact undergoing a review by the new life sciences minister George Freeman (which is undertaken every three years), but he told PME in a recent interview that he was not looking to reform NICE, but rather have it work more closely with the UK drugs body the MHRA and pharma to use the government’s new early access to medicines scheme to help speed up approval times.
Drug pricing: the elephant in the room
NICE may not, however, be the primary problem. The elephant in the room for pharma is how it prices its medicines, and whether this process is fair in the current economic environment, and genuinely relates to the R&D costs inherent in making new medicines.
This has been inflamed recently with some eye-watering prices for new cancer drugs, with Roche’s Kadclya’s £90,000 price tag earning the ire of NICE and even several UK breast cancer charities as being too high for the NHS to afford (the drug however has not been de-listed from the CDF).
When asked by PME whether it could lower its prices, the Swiss firm said its prices matched the level of costs and risk the company undertook when it develops every new treatment: “Medicine is increasingly complex and new treatments are often used in small, highly targeted populations, and in combination with each other,” a spokesman for the firm said.
He added: “If we want to continue the rapid scientific progress of recent years in the most difficult-to-treat diseases, then we need to be prepared to fund this high risk model of drug discovery. We know from our own experience that for every clinical success story there are many examples of disappointment. For this model to be sustainable we need to ensure that high risks are rewarded appropriately.”
The ABPI’s Catchpole maintains that the onus is on NICE, not the industry. He said: “The threshold that NICE applies to approve medicines is out of date and out of step with what the general public perceive is appropriate to pay for life extending cancer medicines.
“This is one reason that the CDF was set up in the first place, by politicians. A sustainable solution must now be found which empowers NICE to approve more new cancer medicines using different criteria and different values that reflect in practice more closely those that are used by today’s NHS to make investment decisions.”
Pharma never reveals how it comes to a price for its medicine – and indeed no pharma company interviewed for this feature would explain how it came to that decision.
But there is an understanding among analysts that as patent protection falls on previous blockbusters – and nothing is in the pipeline to replace these revenues – pharma is intentionally pushing the price up for new oncology treatments to help shore up these losses, meaning it is not always related to its R&D and sales costs.
But are these drugs worth their high price? Many new cancer drugs fail to increase overall survival (OS) in clinical trials, with the vast majority only managing to extend progression-free survival (PFS), which is far less impressive in clinical terms than OS.
And those medicines that can increase OS typically can only do this for several months and require other drugs and chemotherapy regimens alongside it, and yet are priced at a premium for this relatively low efficacy.
The price in relation to a drug’s efficacy, and whether this is cost-effective, is a difficult decision to make, but that is what since 1999 NICE has been established to do, and is internationally respected as the best health technology assessor in the world.
The CDF undermines this process, but after four years NICE has in a way been proven correct – these medicines were not cost-effective as pharma has priced itself out of the Fund, and cuts had to be made.
In fact NHS England has effectively done the job of NICE with its de-listing, but simply taken much longer to do so, and duplicated many of its original decisions.
It’s something of an open secret that a number of pharma firms negotiated with NHS England to save their medicines – not unlike what happens between pharma and the Department of Health over a NICE Patient Access Scheme – although no company would tell PME whether it had secured such a deal.
A sustainable solution must now be found which empowers NICE – The ABPI
The reform challenge
The industry is a business and the CDF will have allowed access to more than £1bn over the six-year life-cycle of the Fund, a considerable funding stream that it would otherwise not have had access to.
But the question of pricing, driven not just by cancer drugs but also by hugely expensive (though impressively effective) hepatitis C treatment over the last year, has been assuming ever-greater importance for some time now and this trend is only set to continue.
The government has already tried to curb medicine prices through the latest five-year PPRS drug pricing deal, introduced at the start of 2014, which has UK pharma firms paying back any money over an agreed growth limit.
But the HSCIC, the NHS data monitoring service, last year published figures for April 2013 – April 2014 that showed the drugs bill had in fact increased from £13.3bn from the previous year to £14.4bn. In fact the cost of medicines rose by 7.6 per cent overall but by 15.1 per cent in hospitals since the year-before period, pushed by cancer medicines and therapies for auto-inflammatory disorders such as arthritis.
Given the size of the NHS funding gap – which healthcare think-tank the King’s Fund says will hit £30bn by 2020 – the push by pharma and patient groups for a sustainable solution to cancer drug access could soon face an even more significant challenge than de-listing.
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A full list of the 16 drugs and 25 licences to be de-listed from 12 March 2015: |
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Sanofi’s Zaltrap (aflibercept): |
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Sanofi’s Jevtana (cabazitaxel): |
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Napp’s Levact (bendamustine): |
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Roche’s Avastin (bevacizumab): |
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Takeda/Millennium’s Velcade (bortezomib): |
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Pfizer’s Bosulif (bosutinib): |
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Merck KGaA’s Erbitux (cetuximab): |
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Bristol-Myers Squibb’s Sprycel (dasatinib): |
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Eisai’s Halaven (eribulin): |
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Novartis’ Afinitor (everolimus): |
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GlaxoSmithKline’s Tyverb (lapatinib): |
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GlaxoSmithKline’s Arzerra (ofatumumab): |
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GlaxoSmithKline’s Votrient (pazopanib): |
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Janssen’s Caelyx (Pegylated Liposomal Doxorubicin (PLD)): |
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Lilly’s Alimta (pemetrexed): |
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Bayer’s Stivarga (regorafenib): |