NICE has reversed its opinion on the use of Bristol-Myers Squibb’s Yervoy (ipilimumab) and Roche’s Zelboraf (vemurafenib) for the treatment of advanced malignant melanoma.

The new final draft guidance recommends the use of Yervoy in people who have received prior chemotherapy.

Zelboraf is also recommended for the treatment of unresectable locally advanced or metastatic BRAF V600 mutation-positive melanoma.

The U-turn came after both manufacturers agreed to supply the treatments at a discounted rate under the terms of separate patient access schemes with the Department of Health.

Professor Carole Longson, Health Technology Evaluation Centre Director at NICE, said the updated guidance was “really good news” for patients with skin cancer.

“Vemurafenib and ipilimumab are breakthrough treatments that can potentially significantly affect prognosis for these patients and we are very pleased that the manufacturers have worked with us so that we are now able to recommend both ipilimumab and vemurafenib,” said Professor Longson.

Since the publication of the first draft guidance, which NICE failed to recommend the use Yervoy due to its £80,000 price tag, BMS provided additional data and analysis surrounding the cost-effectiveness of the drug.

Roche also supplied additional analysis on the effectiveness of the drug in relation to its clinical and cost effectiveness.

NICE has again requested more information from Roche on its skin cancer drug Zelboraf (vemurafenib) after failing to recommend the treatment for a second time in draft guidance.

Its independent Appraisal Committee raised concerns over the evidence supplied from the BRIM3 study and questioned the drug’s long-term benefits.

Professor Carole Longson, Health Technology Evaluation Centre Director at NICE, said the Committee required “further clarification” in order to make a final recommendation to the NHS.

Further analysis was requested by NICE during an earlier draft guidance published in June 2012. Roche provided additional information on the cost effectiveness of the drug – as well as agreeing terms with the DH to supply Zelboraf as part of a patient access scheme.

However, NICE concluded that further data is still needed on the effectiveness of the drug in relation to its cost. It has now asked Roche to supply evidence on disease progression and additional scenario analysis when compared to existing treatments.

“We hope that Roche will be able to provide this additional information so that the Committee can consider it at its next meeting on the topic,” said Professor Longson.

NICE has failed to recommend Roche’s cancer drug Zelboraf (vemurafenib) for the treatment of unresectable locally advanced or metastatic BRAF V600 mutation-positive melanoma in draft guidance.

Its independent Appraisal Committee had uncertainties over the evidence supplied by NICE and deemed the treatment too expensive.

Sir Andrew Dillon, Chief Executive of NICE, said Zelboraf is an “expensive drug” and that its “long term benefits are difficult to quantify”.

Roche’s data came from the BRIM3 trial which compared Zelboraf with a current treatment, dacarbazine. Results showed how Zelboraf was effective for patients with skin cancer with the BRAF 600 mutation.

But its long-term effectiveness was “uncertain”, NICE said, due to patients receiving dacarbazine taking other treatments after their disease had progressed.

Roche had agreed a Patient Access Scheme for the use of Zelboraf on the NHS. However, the discount failed to convince NICE the treatment offers value for money.

It’s estimated that less than 1,000 people in England and Wales each year would be eligible for treatment with Zelboraf.

Bristol-Myers Squibb has expressed its disappointment after the Scottish Medicines Consortium (SMC) failed to recommend its skin cancer drug Yervoy (ipilimumab).

The SMC decided against approving the treatment for advanced (unresectable or metastatic) melanoma in adults who have received prior therapy after questioning its clinical benefits in relation to its cost.

Amadou Diarra, European Vice-President and General Manager, BMS UK and Ireland, said the company would continue to work with the SMC to “enable Scottish patients to access this potentially life-extending treatment.”

Around 1,200 people in Scotland are diagnosed with malignant melanoma each year. Its incidence is rising in the country at an epidemic rate.

Within the appraisal submitted by BMS, the SMC recognised how Yervoy is the first licensed medicine in the UK to demonstrate survival benefits in patients with skin cancer who have received prior treatment.

Data from a pivotal Phase III trial demonstrated how almost half (46%) of patients treated with Yervoy were still alive after 12 months of treatment compared to 25% taking the vaccine gp100.

The median overall survival was 10.1 months in those receiving Yervoy, compared with 6.4 months among those receiving gp100.

However, despite BMS also providing the treatment under the terms of a Patient Access Scheme to reduce the cost of Yervoy, the SMC did not believe it offered value for money to the NHS in Scotland.

“Ipilimumab is a prime example of an innovative medicine that has the potential to offer significantly improved outcomes,” said Amadou Diarra. “We are disappointed that the SMC has failed to recognise the value of Ipilimumab.”

Since it was licensed in Europe in July last year, eligible patients in England have been able to receive the treatment. During the same period, a number of patients have attempted to access Yervoy through an Individual Patient Treatment Request (IPTR). But, as far as BMS is aware, no IPTRs have been approved.

Leigh Smith, Chair of the Melanoma Action and Support Scotland, called the decision “incredibly disappointing” and said the decision by the SMC will drive patients south of the border.

“It leaves many Scottish patients suffering from this devastating disease with no option but to consider moving to England where funding for the treatment can potentially be accessed,” she said. “We hope that the SMC will consider all options available that might enable Scottish patients to benefit from this treatment.”

NICE has failed to recommend Bristol-Myers Squibb’s (BMS) Yervoy (ipilimumab) for advanced melanoma, deeming its £80,000 price tag too costly.

NICE’s Appraisal Committee based its decision on clinical data that suggested the drug could be very effective for a small percentage of patients with advanced skin cancer who have received prior chemotherapy – but it was unknown how long this effect would last.

Sir Andrew Dillon, Chief Executive of NICE said: “We need to be sure that new treatments provide sufficient benefits to patients to justify the significant cost the NHS is being asked to pay.”

Clinical specialists said that approximately 30% of people treated with the medicine would have improved survival, with 10% potentially experiencing long-term benefits.

Sir Andrew added: “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.”

The Committee also cited that Yervoy is associated with a number of adverse reactions including diarrhoea, rash, fatigue, nausea, vomiting, decreased appetite, and abdominal pain.

BMS expressed its disappointment at NICE’s rejection, and have stated it will submit further evidence “in the hope that NICE will reconsider this decision so that all patients with metastatic melanoma can access this potentially life‐extending treatment”.

“In a deadly disease with no standard of care, where inclusion in a clinical trial has been considered one of the few treatment options available to patients, Yervoy represents a significant innovation in treatment,” said Amadou Diarra, European Vice President and General Manager at BMS UK.

Dr Pippa Corrie, Consultant Medical Oncologist at Cambridge University Hospitals NHS Foundation Trust, commented: “Treatment for metastatic melanoma is a huge unmet need, with many patients facing a life expectancy of 6‐9 months. 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.”

Consultees are now able to comment on the preliminary recommendations which are available for public consultation. The manufacturer will be able to reduce the acquisition cost of £80,000 to the NHS for ipilimumab by proposing a Patient Access Scheme.

BMS gained approval to market Yervoy in the US in March 2011, with an approval from the European Commission in July. The drug was launched in the UK in August 2011, becoming the first licensed treatment for advanced skin cancer since the 1970s.

There are approximately 40,000 deaths worldwide from skin cancer, with the number of cases predicted to double from 138,000 a year to 227,000 by 2019.

Mela Sciences has received CE Mark approval for MelaFind, a handheld diagnostic imaging device for the early detection of skin cancer.

The company initially intends to market in Germany, which has the highest incidence of melanoma in Europe.

The new scope is designed to help dermatologists gain more accuracy in evaluating abnormal skin moles in order to identify melanoma.

The non-invasive MelaFind technology acquires and displays multi-spectral digital images of pigmented skin lesions and uses automatic image analysis to help spot lesions less than 2.2cm in diameter, which can then be considered for biopsy.

The approval is based on data gathered from a pivotal trial involving 1,383 US patients, demonstrating 98% accuracy.

There is currently no cure for advanced melanoma, but it is virtually 100% curable if detected early.

Melanoma rates in Germany have doubled over the last decade and the national mortality rate from the disease is the highest in Europe. More than 20,000 Germans are expected to be diagnosed with melanoma by 2016.

Dr Joseph Gulfo, President and CEO of Mela Sciences, said: “With more than 81 million people, Germany represents a significant opportunity for the company and an ideal market to launch MelaFind in the EU.”

Shares in the company rose by 70% following the European approval, which has led to hopes that the device will soon be approved in the US. Mela previously submitted a PMA application to the FDA for MelaFind in June 2009, but is still awaiting the Agency’s decision.

Based in New York, Mela Sciences specialises in dermatology and developing devices to aid in the early detection of melanoma.

Yervoy (ipilimumab, pictured) has become the first licensed treatment for advanced skin cancer launched in the UK since the 1970s.

The Bristol-Myers Squibb drug has been shown to almost double life expectancy after a year in Phase III trials and works by stimulating the body’s own immune system to fight cancer.

Dr Paul Lorigan, Senior Lecturer in Medical Oncology, the Christie NHS Foundation Trust, says the license ‘represents a real advance’ in treating skin cancer.

NICE is still conducting its appraisal of Yervoy for use on the NHS, although patients can apply to the Government’s Cancer Drugs Fund to receive the injection.

In the pivotal Phase III clinical trial, almost half (46%) of patients were still alive after a year when receiving Yervoy, compared to a quarter who were treated with a vaccine called gp1003.

Patients are injected four times with Yervoy at a cost of around £75,000. Despite the high cost of the treatment, Dr Lorigan insists the authorisation by the EMA is a “stride forward” for patients.

“The authorisation of ipilimumab represents a real advance in the treatment of patients with advanced melanoma because it is the first treatment to be licensed in the UK for 30 years that may extend patients’ life expectancy,” said Dr Lorigan.

The current standard of treatment, dacarbazine, has been used in the UK for the last three decades.

Yervoy has also been approved by the FDA in the US.

Final NICE guidance on the Ambulight photodynamic therapy (PDT) device to treat non-melanoma skin cancer says there is not enough evidence to support its routine use in the NHS.

However, the device from Scottish company Ambicare Health remains one of the potential options while the evidence base is developed further.

Ambulight PDT consists of a battery-powered, disposable light-emitting device that is stuck to the skin with a disposable sticking plaster. It delivers an ambulatory therapy that can be used in the home or the community, whereas conventional PDT requires a hospital appointment.

In addition, Ambicare claims that the device’s lower irradiance makes it less painful for the patient than PDT sources.

The Medical Technologies Advisory Committee decided there was some evidence for the effectiveness of Ambulight PDT, but said the evidence on its use was too limited to support a recommendation for its routine adoption.

In particular, the cost data were too varied: the cost difference between Ambulight PDT and conventional PDT ranged from a saving per patient of £195 to an increase of £536, making firm conclusions difficult.

Professor Carole Longson, Director of the NICE Centre for Health Technology Evaluation, commented: “The management of non-melanoma skin cancers imposes a significant workload on both primary and secondary care services, and therefore a device that offers PDT therapy in a community setting has the potential to have a positive impact on service provision.

However, she said, it was “uncertain” to what extent the relevant “changes in service provision” would result in benefits, as the evidence for the device’s efficacy was “of limited quantity”. NICE recommended that the device remain a treatment option in order to generate further evidence.

 
Ambulight PDT

Bristol-Myers Squibb’s skin cancer drug Yervoy (ipilimumab) is expected to reach blockbuster status after gaining US approval.

The FDA gave the thumbs up to the skin cancer treatment as a first and second line option for advanced, inoperable or metastatic melanoma following impressive Phrase III results.

Richard Pazdur, Director, Office of Oncology Drug Products, FDA, says Yervoy will help patients “live longer” and analysts have now predicted billion dollar sales.

At a cost of $120,000 for a full course of treatment, Yervoy will become one of the most expensive treatments on the US market with sales forecasts ranging from $820 million to $1.7 billion by 2015.

Yervoy is currently under review by the EMA after BMS’ submission in July 2010. But it has been given the green light for use in America after Phase III data showed median survival rates increased by 10 months.

BMS says the drug works by allowing the body’s immune system to recognise, target, and attack cells in melanoma tumours.

“The FDA approval of Yervoy is the culmination of more than 14 years of research and development by our dedicated development teams and clinical trial investigators,” said Elliott Sigal, Executive Vice President, Chief Scientific Officer, and President, Research & Development, Bristol-Myers Squibb.

“Yervoy is the first FDA-approved compound from our robust immuno-oncology pipeline, which comprises a variety of other compounds with the potential to harness the patient’s immune system to fight cancer.”

The FDA fast-tracked the drug last year but delayed its decision after it requested further information on the drug’s safety profile. The Agency has issued a ‘black box’ warning after severe to fatal autoimmune reactions were seen in 13% of patients treated with Yervoy.

Side-effects include enterocolitis, hepatitis, dermatitis, neuropathy and endocrinopathy, and the FDA has included a Risk Evaluation and Mitigation Strategy to inform healthcare professionals and a medication guide to inform patients about potential risks.

There are an estimated 40,000 deaths worldwide from melanoma, with the number of cases predicted to double from 138,000 a year to 227,000 by 2019.