The decision by the UK's cost watchdog to reject Bristol-Myers Squibb's new melanoma drug Yervoy has been greeted with dismay by the company and patient groups.

In a provisional draft guidance published this morning, the National Institute for Health and Clinical Excellence has decided against recommending payment by the National Health Service for Yervoy (ipilimumab) for advanced malignant melanoma in people who have received prior chemotherapy. NICE acknowledges that the drug met the criteria for being a life-extending, end-of-life treatment but considers that "the magnitude of additional weight that would need to be assigned to the original quality-adjusted life year (QALY) benefits for people with advanced melanoma would be too great for ipilimumab to be considered a cost-effective use of NHS resources".

Yervoy costs £80,000 per patient

NICE said that ipilimumab costs an average of around £20,000 per dose (each patient receives four), adding that "the most plausible ICER (the cost per year of improved health) would fall between £54,000 to £70,000 per QALY gained".However, "because of the lack of data available on the long-term benefits of treatment, further analyses are unlikely to confirm the true ICER estimate, which could be significantly higher".

Sir Andrew Dillon, NICE's chief executive, noted that the data submitted by B-MS came from a trial that did not compare ipilimumab with the drugs currently used to treat people with advanced melanoma, ie carboplatin-based chemotherapy or dacarbazine. While the results did show the drug could potentially be very effective "for a small percentage of patients…the follow-up from the trial was too short to determine how long this effect would last", he added.

Sir Andrew noted that clinical specialists also told NICE's independent appraisal committee that only 30% of people treated with ipilimumab would have improved survival, with only 10% potentially experiencing long-term benefits. “Unfortunately, no patient characteristics or biomarkers have yet been identified to help identify this small group of people most likely to gain long-term benefit from receiving ipilimumab", he added, going on to state that Yervoy is also associated "with a number of adverse reactions including diarrhoea, rash, fatigue, nausea, vomiting, decreased appetite and abdominal pain which can significantly affect a patient’s quality of life".

The NICE boss concluded by saying while consultees comment on the  recommendations, "the manufacturer can also consider whether it wishes to reduce the acquisition cost to the NHS of the drug by proposing a patient access scheme. Ipilimumab currently costs around £80,000 per patient whether the treatment is effective for them or not".

NICE methods fail to capture value of Yervoy

Unsurprisingly, B-MS said it is "extremely disappointed". Amadou Diarra, head of the firm's UK operations, said "we do not believe that the current cost/QALY method used by NICE has fully captured the value of Yervoy", adding that the firm believes the drug represents real value for money to the NHS". He went on to say B-MS will be submitting further evidence "in the hope that NICE will reconsider this decision".

Pippa Corrie, a consultant oncologist at Cambridge University Hospitals NHS Foundation Trust, was also non-plussed. Noting that treatment for metastatic melanoma "is a huge unmet need, with many patients facing a life expectancy of six-nine months, she said Yervoy "is the first treatment to demonstrate an overall survival benefit in this dreadful condition in a Phase III clinical trial, and it therefore represents a major breakthrough".

Dr Corrie says that "whilst the NICE decision is predictable, it is disappointing. It is essential that we all work to avoid any negative impact on facilitating patient access to this drug.  Our patients have waited too long already".

Patients 'shattered' by decision

Patient support group Factor 50 and UK skin cancer charity issued a joint statement saying that standard treatments that have been available since the 1970s "are ineffective and to deny this drug to patients, many of whom are young and with very young families, has undoubtedly handed them down a death sentence". The groups added that patients waiting for the NICE decision "were all hoping and praying that it would be favourable.   Understandably, they are completely shattered, but have vowed, in the time they have left, to try and counter the decision".

Yervoy has made a stunning start in the USA and contributed an impressive $95 million to B-MS sales in the second-quarter, just a few weeks after launch. The drug received European approval in July 2011 and a B-MS spokeswoman told PharmaTimes World News it has been commercialised in Germany, Austria and Sweden, while a number of other countries are still in reimbursement negotiations.

Analysts are not surprised by the decision and Gustav Ando, director of healthcare at IHS Global Insight, said his firm "had long questioned whether a drug with such a high initial price point could feasibly reach the cost-effectiveness threshold which guides NICE’s decision".