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The new final draft guidance recommends the use of Yervoy in people who have received prior chemotherapy.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Since the publication of the first draft guidance, which NICE failed to recommend the use Yervoy due to its £80,000 price tag, BMS provided additional data and analysis surrounding the cost-effectiveness of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from Roche on its skin cancer drug Zelboraf (vemurafenib) after failing to recommend the treatment for a second time in draft guidance.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Further analysis was requested by NICE during an earlier draft guidance published in June 2012.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.

Roche’s Zelboraf (vemurafenib) can extend the lives of patients with advanced melanoma by more than a year, data from a phase III trial has shown.

Patients given Zelboraf showed a median overall survival of 13.2 months, compared to 9.6 months with chemotherapy.

An abstract of the trial report stated that the increased survival meant a 38% reduction in the risk of death from melanoma.

A previous controlled trial, which formed the basis for the drug’s FDA approval in 2011, was halted early so that patients in the chemotherapy arm could be given Zelboraf for their clinical benefit.

Zelboraf has been hailed as a leading example of ‘personalised’ medicine as it targets the BRAF gene mutation, carried by about half of all melanoma patients.

Jennifer Low, Group Medical Director in Product Development for Genentech, Roche’s US subsidiary, commented: “The life expectancy for these patients isn’t very long, so they have an opportunity to have therapy that on average improves survival by a really significant amount.”

Roche is also testing Zelboraf as a treatment for other types of cancer, alone or in combination with other drugs.

Roche has launched its skin cancer drug Zelboraf (vemurafenib) in the UK for adults with unresectable or metastatic melanoma who test positive for the BRAF V600 genetic mutation.

The treatment was licensed by the European Commission last month for use as a single-agent therapy after it demonstrated in clinical trials that patients lived an average of 13.2 months longer than with standard chemotherapy.

Professor Alan Ashworth, CEO, Institute of Cancer Research, said it was pleasing that patients would be able to benefit from the personalised medicine.

Alongside Zelboraf, Roche has also launched a companion biomarker test to identify patients who could benefit from the advanced melanoma treatment.

In clinical trials conducted in the UK, patients with BRAF-mutant advanced cancers were shown to be almost nine times more likely to respond to Zelboraf than to standard chemotherapy.

The FDA approved the use of the cancer drug for a similar indication in August 2011. NICE is currently appraising the treatment with guidance expected to be issued in October.

Analysts have already predicted that annual sales of the drug may reach up to $1.5bn.

Roche’s Zelboraf (vemurafenib) has been approved by the European Commission as a monotherapy for the treatment of adults with BRAF V600 mutation positive unresectable or metastatic melanoma.

The skin cancer treatment is the first and only personalised medicine that allows patients with BRAF V600 mutation-positive metastatic melanoma to live significantly longer.

Hal Barron, Chief Medical Officer and Head, Global Product Development, said the approval is “important news” as Zelboraf “significantly improves patient survival”.

Zelboraf is designed to target and inhibit mutated forms of BRAF found in approximately half of all cases of skin cancer.

In pivotal clinical trials, it demonstrated patient survival in previously untreated and treated those with advanced melanoma who tested positive for BRAF V600 mutations in Roche’s cobas 4800 BRAF V600 Mutation Test.

Data from the Phase III BRIM3 trial showed that the risk of death fell by 63% in people receiving Zelboraf compared to those receiving standard first-line treatment.

Post-hoc analysis of BRIM3 data with a follow-up compared to previous analyses also showed Zelboraf significantly improved survival by a median overall survival (OS) of 13.2 months compared to 9.6 months for chemotherapy.

Last year, the medication became the first and only personalised medicine approved by the FDA for the same indication. It has also recently been approved for use in Switzerland, Brazil, Israel, Canada and New Zealand.

The European Medicines Agency (EMA) has recommended the marketing authorisation of Roche’s drug Zelboraf (vemurafenib) as a treatment for metastatic or inoperable melanoma with BRAF V600 mutations.

The drug, a protein-kinase inhibitor, improves survival times in patients with advanced skin cancer by about three months relative to the standard existing treatment.

Zelboraf is a personalised medicine linked to Roche’s cobas BRAF Mutation Test, which selects patients for treatment with a number of specific anti-melanoma drugs.

The EMA’s Committee for Medicinal Products for Human Use (CHMP) concluded that the benefits of Zelforaf outweighed the risk of causing secondary skin cancers, including squamous cell carcinomas.

While early-stage melanoma can be treated effectively by surgery, metastatic melanoma causes 15,000 deaths worldwide each year. Only a quarter of patients survive beyond 12 months.

In clinical trials, Zelboraf was found to improve progression-free survival times by around four months and overall survival times by about three months relative to the standard treatment (dacarbazine).

The CHMP decided that the risks of using Zelboraf were acceptably low, and that Roche had put in place an appropriate risk management procedure for doctors, including monitoring and treatment of secondary cancers.

Paul Brown, Head of Roche Molecular Systems, commented: “The cobas BRAF Mutation Test has improved sensitivity, accuracy and speed compared to other commonly used, unapproved detection methods. With a personalised medicine now available, all people diagnosed with inoperable or metastatic melanoma should be tested to help determine the best options for treatment.”

Zelboraf was approved by the FDA in August 2011.

Bristol-Myers Squibb and Roche have entered into a clinical collaboration agreement to conduct studies in metastatic melanoma.

The companies intend to conduct an exploratory Phase I/II study to evaluate the safety and efficacy of combining CTLA-4 inhibitor Yervoy (ipilimumab) and BRAF inhibitor vemurafenib. Further studies may follow, depending upon the results that are found.

Brian Daniels, Senior Vice President, Development and Medical Affairs, Bristol-Myers Squibb stated that the company is excited to be able to “evaluate the potential that together Yervoy and vemurafenib could improve outcomes for melanoma patients”.

“We have made significant progress in treating metastatic melanoma and hope to further improve outcomes by combining two agents that target this deadly disease in different ways,” added Hal Barron, Chief Medical Officer and Head, Global Product Development, Roche.

Yervoy is licensed in the US for the treatment of patients with inoperable or metastatic melanoma.

Vemurafenib is designed to selectively inhibit a cancer-driving mutated form of the BRAF protein and is currently being developed under a collaboration agreement between Roche and Plexxikon, a member of the Daiichi Sankyo Group. Roche is also currently conducting trials into the drug’s potential as a treatment for people with metastatic or unresectable papillary thyroid cancer.

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Roche has submitted a Marketing Authorisation Application to the EMA for vemurafenib (RG7204, PLX4032) to treat people with BRAF V600 mutation-positive metastatic melanoma.

The application is based on the BRIM2 and BRIM3 studies that evaluated vemurafenib in people with BRAF V600 mutation-positive metastatic melanoma and both met their primary endpoints.

Hal Barron, Chief Medical Officer and Head of Global Product Development, says Roche has “worked swiftly” to advance the drug’s development programme in patients who have “limited treatment options”.

The company also submitted a New Drug Application to the US Food and Drug Administration on the same day as the European application.

BRIM2 is a global Phase II study that enrolled 132 patients with previously treated BRAF V600 mutation-positive metastatic melanoma. Data showed that vemurafenib shrank tumours in more than half (52%) of trial participants and those involved lived a median of 6.2 months without their disease getting worse.

The Phase III BRIM3 is a global study comparing vemurafenib to dacarbazine chemotherapy, a current standard of care, in 675 patients. It met its two co-primary endpoints and showed that participants lived longer and also lived longer without their disease getting worse compared to those who received dacarbazine chemotherapy.