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The new final draft guidance recommends the use of Yervoy in people who have received prior chemotherapy.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Since the publication of the first draft guidance, which NICE failed to recommend the use Yervoy due to its £80,000 price tag, BMS provided additional data and analysis surrounding the cost-effectiveness of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.

Incivo, Victrelis and Mepact win recognition at the 2012 UK Prix Galien Awards.

Two new medicines for the treatment of Hepatitis C have won the 2012 UK Prix Galien Innovative Product
Award. Incivo (Janssen) and Victrelis (MSD) fought of stiff competition to win the prestigious prize at London’s House of Commons. The chairman of the judging panel, Professor Sir Michael Rawlins, said the treatments provided a perfect example of how the pharmaceutical industry can “demonstrate and justify its place in healthcare by innovating for change and showing real gains to the world.”

The ceremony also saw Takeda become only the third winners of a Prix Galien Award for orphan drug development. Mepact – for the treatment of osteosarcoma, a rare malignant bone tumour – won the Orphan Drug Award.

UK Prix Galien 2012
The UK Prix Galien, organised and managed by the specialist market access consultancy WG Consulting – which owns the UK franchise – is held every two years. The 2012 awards were hosted by former shadow Minister for Health Kevin Barron MP, who was the event’s Parliamentary Sponsor. Barron, who is currently co-Chair of the Associate Parliamentary Health Group, said: “It’s a privilege to be able to witness, at first hand, just a glimpse of the deep volumes of medical innovations being developed here in the UK. As an MP, I’ve had a long-standing professional acquaintance with UK pharma. I know and recognise the many
benefits UK medicines have brought – and continue to bring – to patients all over the world. The sector’s continued commitment to the development of medicines to tackle disease, improve health outcomes and extend life is both remarkable and humbling.”

Barron said there was political consensus that driving improvements in health outcomes across all major diseases is a key priority for the NHS – and this focus had been reflected in the 2012 finalists. “It’s interesting to note that the shortlisted entrants for the 2012 UK Prix Galien show that pharmaceutical innovation is aligned with many of the priority needs identified in the NHS Outcomes Framework. Finalists include innovations for the treatment of diseases in cardiovascular, hepatology, mental health, neurology, gastroenterology and oncology. In addition, Prix Galien’s recognition of the industry’s attempts to treat rare, orphan diseases, once again underlines the very human value of R&D.”

Value-based message
The architect of the NHS Outcomes Framework, former Health Secretary Andrew Lansley, also addressed the audience. Attending his fourth consecutive UK Prix Galien, Lansley said: “Every time I come to this event I hear about fascinating innovations that I know are going to be at the heart of the health service for years to come. I’ve met – and continue to meet – patients that have benefited directly from innovations that I’ve previously heard about at Prix Galien. The HPV vaccination programme we have been able to roll out is just one example of that. So it’s a privilege to be here.”

Lansley said that recognising and rewarding innovation is a key Government priority – and that the publication of Innovation Health and Wealth last December was part of a consistent value-based message
it wanted to send to the NHS. “That message is that as you, the pharmaceutical industry, bring forward new treatments that will clearly add value and improve the quality of healthcare for patients then the NHS should be at the forefront, internationally, of demonstrating that value. Our health service can be an exemplar and inspiration to people around the world because of its capacity to demonstrate the effectiveness of new treatments when they are used within the NHS.”

Lansley praised the UK pharma industry, highlighting the value its innovations bring both to the economy and to patients worldwide. “What you are doing is part of how this country will pay its way in the future,” he said. “And it has the added value of knowing that, in the process, we can give patients in this country access to the very best healthcare anywhere in the world.”

The recognition of innovation that can lead to improved health outcomes is a core aim of Prix Galien, as outlined by Professor Sir Michael Rawlins, who announced the winners. “Prix Galien is about honouring excellence in pharmaceutical research and development,” said Professor Sir Michael. “It is about recognising the contribution that new medicines can make to the lives of people with life-threatening conditions. It is about celebrating the achievements of all those individuals – working as teams – upon whom we rely for the discovery and development of new medicines. Most will be unknown to us – but we all owe them a huge debt of gratitude.”

Innovative Product Award
The prestigious Prix Galien medal for innovation was jointly awarded to Janssen and MSD for their respective hepatitis C treatments Incivo and Victrelis. In the UK, it is estimated that there are between 200,000 and 400,000 people chronically infected with hepatitis C virus. This may lead to liver cancer as well as other serious liver diseases. Infection with the hepatitis C virus poses a substantial global health burden, and is responsible for 40% of all cases of end-stage cirrhosis, 60% of hepatocellular carcinoma and 30% of liver transplants.

Professor Sir Michael Rawlins said: “Hepatitis C virus has become an enormous area of need globally, with many patients unaware that they are infected. The consequences of this virus are considerable and burdensome to both patients and the healthcare system; current treatments remain ineffective in a significant number of cases whilst being unpleasant and poorly tolerated by patients themselves.

“Hepatitis C infection is a perfect example of where the pharmaceutical industry can demonstrate and justify its place in healthcare by innovating for change and showing real gains to the world. It is for this reason that the panel felt that both Janssen and MSD should be celebrated and congratulated for their part in addressing the ongoing challenge in managing HCV and its associated complications.”

Brilique (AZ) and Resolor (Shire) both received commendations. Gilenya (Novartis), Xarelto (Bayer), Xeplion (Janssen), Xgeva (Amgen), Yervoy (Bristol-Myers Squibb), Zelboraf (Roche) and Zytiga (Janssen) were all shortlisted.

Orphan Drug Award
The Orphan Drug Award was introduced as a dedicated category at 2008 UK Prix Galien. There had previously been a special award for orphan products in 2006. The term ‘orphan condition’ is used to describe conditions that affect a very small number of patients in a given population – many of which are either untreatable or treated very inadequately. It is estimated that there are 6,000 orphan diseases – which, in total, affect about 30 million EU citizens.

“For orphan diseases that are potentially treatable with medicines, pharmaceutical manufacturers face a number of hurdles – including concerns about the size of the market and difficulties because of the small numbers of patients – in their development,” said Professor Sir Michael.

The 2012 Orphan Drug Award was won by Mepact from Takeda. Mepact (mifamurtide) is for the treatment of osteosarcoma, a rare malignant bone tumour – mainly of children and adolescents – that affects fewer than 1 per 10,000 individuals in the EU. This is equivalent to 150 children and young adults each year in the UK. Tumours most frequently occur in the long bones and are highly aggressive with a propensity to metastasise, particularly to the lung. If left untreated, the primary tumour will undergo local and systemic progression, leading to death within months.

“To investigate the role of this immune modulator in osteosarcoma required extensive and complex trial design with careful implementation of the study programme,” said Professor Sir Michael. “Apart from its novel mechanism of action – and clear evidence of its clinical effectiveness – the jury were also extremely impressed that such an advance in the management of osteosarcoma represents the first significant change in outcomes in 10–20 years of managing this disease. That Takeda managed to undertake the clinical development of this product – in such a niche indication – is hugely to their credit.”

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.

Roche saw Group sales fall 10% in Swiss francs (CHF) to 42.5 billion in 2011 due to the appreciation of the franc, and revenue decrease by 12% in its Pharmaceuticals Division after sales of Avastin and Tamiflu fell.

Pharmaceutical sales accounted for 32.7bn CHF after MabThera generated 6bn CHF (+8%), Herceptin 5.2bn CHF (+9%) and sales of Lucentis increased by 23% to 1.5bn CHF.

Severin Schwan, Roche CEO, says the Group achieved its “sales and earnings targets” in 2011 and made “significant progress with our pipeline”.

The company expects to record single-digit sales growth for the Group and its pharma division in 2012 after achieving several important regulatory milestones in Q4 of 2011.

Group sales in constant currencies were up 1% after its pharma division, excluding Tamiflu, grew at the same rate. Sales were up 2% in constant currencies in the US to 12.2bn Swiss francs and in international markets by 3% to 8.5bn. However, pharmaceutical sales in Western Europe dropped 3% to 8.2bn and in Japan by 6% to 3.8bn.

Core operating profit increased 6% in constant currencies, core earnings per share was up by 11% and net income jumped 26% to 9.5bn CHF in 2011.

Sales of cancer medicines Xeloda (1.3bn CHF; +8%), Tarceva (1.2bn CHF; +7%) and Zelboraf (31m) – recently launched in the US – were called “encouraging”. But a 7% decrease in sales of Avastin, NeoRecormon (-23%), Bonviva (-22%) and CellCept to (-14%) were put down to US health reforms, European austerity measures and Japanese biennial price cuts resulting in a negative growth impact of 295m CHF.

“With 17 positive late-stage clinical trials in 2011, we continue to build our future business with innovative products,” said Severin Schwan. “For 2012 we expect Group sales to grow at a low to mid-single-digit rate and we have set ourselves the target of high single-digit Core Earnings per Share growth.”

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.

Roche has posted solid sales performance in the first nine months of 2011 with overall group activity up 2% to 31.5bn Swiss francs.

Sales in the pharmaceutical division grew 1% after growth of key medicines and markets, particularly in the international region where a 6% increase was recorded.

Severin Schwan, Roche CEO, says the Group is “on track to achieve our targets for 2011” after recording results in line with expectations.

The Group confirmed it is expecting low single digit growth this year and is still targeting Core EPS growth of approximately 10% despite a challenging environment and global health reforms.

US pharmaceutical sales were up 1% and driven mainly by demand for Lucentis, Rituxan and Actemra. But the company suffered an expected negative impact in sales of Avastin (pictured) after the uncertainty around the metastatic breast cancer indication in the US.

Sales were down 4% in West Europe, primarily due to government austerity measures, and 2% in Japan after the affects of the earthquake in the country in March, the company said. Although an increasing demand for products in China (+28%), Venezuela (+88%) and Brazil (+16%) helped boost figures internationally.

In the same period, Roche also reported positive data from seven clinical studies, a number of which have already formed the basis for regulatory filings and approval in Q3; including the launch of skin cancer medication Zelboraf and companion diagnostic cobas BRAF Mutation Test following FDA approvals in August and Tarceva (pictured) in the EU for EGFR-mutated non-small cell lung cancer.

“The successful US launch of our new melanoma medicine Zelboraf and the diagnostic cobas BRAF test has strengthened our leading position in personalised healthcare,” said Severin Schwan. “The good results we have achieved with new medicines in seven late-stage clinical trials so far this year further enhance our prospects for future growth.”