Bristol-Myers Squibb has expressed its disappointment that the National Institute for Health and Care Excellence (NICE) has issued draft guidance which effectively denies access to Yervoy®q (ipilimumab) for NHS patients with previously-untreated advanced (unresectable or metastatic) melanoma, not involved in clinical trials. Ipilimumab is currently recommended by NICE for the treatment of adults with previously-treated advanced melanoma2 and, in November 2013, European regulators extended its licence to include use in previously-untreated patients, recognising both its potential to significantly increase overall survival and the unmet need in this patient population. Unless reversed, this decision will restrict access to all NHS patients that have not had prior therapy. Ipilimumab is a fully human monoclonal antibody that works by stimulating the patient's own immune system to fight the cancer4 and is one of the most significant treatment advances for this disease in many years.
The National Cancer Drug Fund (NCDF) panel has reviewed ipilimumab in previously-untreated patients and decided to refer it for baseline commissioning by NHS England. This is a six month process, during which time patients will not be able to access ipilimumab through the National Cancer Drugs Fund.
"Clinically, there is little difference between pre-treated and untreated advanced melanoma patients and ipilimumab is licensed to treat both types," said, Professor John Wagstaff, Consultant Oncologist at the South West Wales Cancer Institute & Swansea School of Medicine. "Today's decision will be disappointing news for many patients with advanced melanoma who have not received prior treatment, leaving them without immediate access to this innovative therapy. Ipilimumab has demonstrated its ability to increase overall survival in this cancer, in some cases having a long-term effect on the survival of previously-treated patients. Making it available as a first treatment option should therefore be seen as an important step in helping to maximise survival in this disease."
In previously-treated advanced melanoma, ipilimumab has been shown to provide durable long-term survival in some patients.1 Upon its approval in 2011, it became the first treatment to demonstrate an overall survival benefit in a Phase III clinical trial in this patient population. In the pivotal Phase III clinical trial assessing ipilimumab in previously-treated patients, published in the New England Journal of Medicine in 2010, 46% (63 people out of 137) of patients were still alive at one year in the ipilimumab arm and 25% (34 people out of 136) in the comparator, a vaccine called gp100. The median overall survival was 10.1 months among patients receiving ipilimumab alone, compared to 6.4 months among patients receiving gp100 alone.5 In 2013, Bristol-Myers Squibb announced results from a pooled analysis of survival data taken from previously-treated and previously-untreated patients who received ipilimumab at different doses and regimens, including combinations with other agents (n=1,861).1,6 When looking at survival over time, a plateau in the survival curve began at approximately three years, with a few patients followed for up to ten years. Approximately 22% of patients (95% CI: (20-24%) were alive at three years (number of patients available for analysis at this time point was 254).1,6 The analysis was retrospective and did not include a control arm.
Ipilimumab's use in previously-untreated patients with advanced melanoma is supported by data pooled from Phase II and III studies1, as well as from two retrospective observational studies in previously-untreated advanced melanoma patients who were treated with ipilimumab 3mg/kg monotherapy (studies CA184- 332 and CA184-338).7,8 Available data have demonstrated that, as monotherapy at this 3mg/kg dose, treatment with ipilimumab has the potential to improve the overall survival of patients, irrespective of whether they have received prior therapy or not for their metastatic melanoma.1,5,7,8 The safety profile of ipilimumab in previously-untreated patients is also comparable to that seen in those who have been previously-treated.5,7,8
Around 12,800 people in the UK were diagnosed with melanoma in 2010 year and, although the majority of skin cancers are treatable, in 2011 this disease killed around 2,200 people in the UK.3 Each day more than two young adults aged 15-34 in the UK are diagnosed with malignant melanoma.3 Over the last 30 years, the incidence of melanoma in the UK has more than quadrupled and has risen faster than any of the current top-10 cancers.3 While recent treatment advances are improving outcomes, historically advanced melanoma has been associated with a median survival of just 6-9 months.9
Gill Nuttall, Melanoma UK commented: "Advanced melanoma is a devastating diagnosis, yet treatment options remain severely limited for many patients facing this disease. Unless reversed, this decision by NICE will sadly continue this trend and will leave some patients without a medicine that could potentially help extend their lives."
Commenting on today's decision, Amadou Diarra, European Vice-President and General Manager, Bristol-Myers Squibb UK & Ireland, said "Bristol-Myers Squibb is disappointed in the draft recommendation that NICE has issued and we are committed to doing all we can to ensure that patients ultimately get access to this important treatment as early as possible. Ipilimumab is a pioneering immuno-oncology therapy that has been recognised by European regulators as an important option for advanced melanoma patients who have not received prior therapy. We therefore hope that the significant unmet need and clinical evidence backing this treatment will result in a review of this decision."