NICE recommendation set to leave patients with newly diagnosed advanced melanoma without access to Yervoy® (ipilimumab)

NICE recommendation set to leave patients with newly  diagnosed advanced melanoma without access to Yervoy® (ipilimumab)

- Draft guidance effectively denies access to ipilimumab for NHS patients with previously‐
untreated advanced melanoma who are not in a clinical trial. This decision could leave them
without the option to be treated with this innovative immuno‐oncology therapy which has
the potential to offer long‐term survival in some patients
- Ipilimumab is currently recommended by NICE for the treatment of adults with previously‐
treated advanced melanoma
- Each day, more than two young adults aged 15‐34 in the UK are diagnosed with malignant
melanoma

UXBRIDGE, UK, 25 FEBRUARY, 2014 – Bristol Myers Squibb today expressed its disappointment that the National Institute for Health and Care Excellence (NICE) has issued draftguidance which effectively denies access to Yervoy® (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 cancer 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. Thisis 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 WagstaffConsultant 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. 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. 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).
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.

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."  

4
NOTES TO EDITORS 

About Yervoy®
 (ipilimumab)
Ipilimumab is a fully human monoclonal antibody that works by stimulating the body's own
immune system to fight cancer. Its mechanism of action in patients with melanoma is indirect,
possibly through T‐cell mediated anti‐tumour immune responses.
In July 2011, ipilimumab received a European licence for the treatment of advanced (unresectable
or metastatic) melanoma in adults who have received prior therapy. Ipilimumab is now licensed in
more than 40 countries in this setting. In November 2013, ipilimumab was granted an extension to
its licence to include its use as a treatment for advanced (unresectable or metastatic) melanoma in
adults who have not yet received prior therapy. 

Ipilimumab data in melanoma
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).

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.

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 comparable to that seen in those who have been
previously‐treated.

Ipilimumab has the potential to contribute to durable, long‐term survival in some patients. In 2013 Bristol‐Myers Squibb announced results from a pooled analysis of survival data for 12 studies
(n=1,861) in patients with metastatic or locally advanced or unresectable melanoma who were
treated with ipilimumab at different doses and regimens (including combinations with other
agents).1,6 When looking at survival over time, a plateau in the survival curve was seen at
approximately three years, with follow‐up of up to ten years in a few patients. 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  This pooled analysis was conducted to provide a more precise
estimate of the long‐term survival effect of ipilimumab in patients with metastatic melanoma. It is
comprised of patient‐level data from 12 prospective and retrospective studies, including two
Phase III trials (n=790), eight Phase II trials (n=821), and two retrospective, observational studies
(n=250), which have been or will be reported on as individual studies.1,6 Three studies included OS
follow‐up in some patients for up to ten years. The analysis included both previously‐treated
(n=1,257) and previously untreated patients (n=604) who received ipilimumab at different doses
and regimens.1,6 Some patients were also treated in combination with other agents e.g. DTIC. The
majority of patients received the licensed dose of ipilimumab at 3 mg/kg (n=965) or the unlicensed
dose at 10 mg/kg (n=706).  Ipilimumab was given every 3 weeks for 4 doses, and most studies
included the option to receive either ipilimumab retreatment or ipilimumab maintenance therapy
for eligible patients. Median OS for the entire population was 11.4 months (95% CI: 10.7–12.1).1,6
The analysis was retrospective and did not include a control arm. 

Safety information on ipilimumab4

The safety profile of ipilimumab is considered to be related to its mechanism of action as an
immunotherapy. In a pivotal Phase III clinical trial, drug‐related adverse events related to the study
drug were mostly immune‐related adverse events (irAEs). Immune‐related adverse events
described to date have included gastrointestinal, skin, liver, endocrine or nervous systems. The
most frequently reported adverse events (≥ 10% of patients) included diarrhoea, rash, pruritus,
fatigue, nausea, vomiting, decreased appetite, and abdominal pain. The majority were mild to
moderate.  The safety profile of ipilimumab in previously‐untreated patients is comparable to that
seen in those who have been previously‐treated. Early diagnosis and appropriate management of
adverse events using established product‐specific guidelines are essential to minimise
complications.

Ipilimumab and the National Cancer Drugs Fund 
In a recent review, the National Cancer Drugs Fund (NCDF) Panel noted that Bristol‐Myers Squibb
should seek baseline commissioning for first‐line (previously‐untreated) ipilimumab in advanced
melanoma, rather than ipilimumab being funded through the NCDF. This was due to the fact that
funding is currently in place for second‐line (previously‐treated) treatment and the NCDF panel
considers the impact to be cost neutral. While this presents the possibility for patients to access
ipilimumab through NHS England's baseline commissioning system, as this process takes 6 months,
untreated patients will have no access to ipilimumab in the interim period. 


About Bristol‐Myers Squibb 
Bristol‐Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop
and deliver innovative medicines that help patients prevail over serious diseases.


For more information, please contact: 
Emma Wright
External Communications Manager
Bristol‐Myers Squibb UK
T: +44 (0)1895 523 619
M: +44 7581 474113
E: [email protected]

Tim Cockroft
RM Eclipse
T: +44 (0)207 861 2805
M: +44 (0)7957 325 583
E: [email protected] 
###
 

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