Final draft guidance from NICE recommends Xarelto (rivaroxaban) to treat pulmonary embolism (PE) and deep vein thrombosis (DVT) and prevent their recurrence.

The Bayer drug offers an alternative to warfarin, the standard treatment for dangerous internal blood clotting.

Xarelto presents fewer dose management challenges than warfarin, and has fewer interactions with other drugs and with foods.

DVT, an abnormal blood clot formation in the leg or pelvis, can lead to PE and other dangerous circulatory malfunctions that cause disability or death. Risk factors for DVT include prolonged travel and/or immobility.

Suspected PE is treated with an anticoagulant, usually initial injections of heparin followed by longer-term oral doses of warfarin. However, warfarin presents complex dose adjustment challenges and can interact dangerously with other medications and with foods.

NICE determined that Xarelto was cost-effective both as a treatment for PE and DVT over three, six or 12 months and as a lifelong treatment to prevent the recurrence of PE or DVT.

Professor Carole Longson, NICE Health Technology Evaluation Centre Director, said: “The regular monitoring and dose adjustment needed with warfarin, which needs regular visits to hospital or GP appointments, can be costly and inconvenient. Also, because warfarin has many drug interactions, it may be unsuitable for people with comorbidities. In addition, the Committee heard that warfarin has various food interactions which often require people to adjust and monitor their diet.

“Rivaroxaban therefore represents a significant potential benefit for people with PE and DVT because it avoids the need for initiation with heparin and the subsequent transition to warfarin.”

Final NICE guidance is expected in May 2013.

The Atrial Fibrillation Association has welcomed NICE’s recommendation in final draft guidance of Eliquis (apixaban) for the prevention of stroke and systemic embolism in certain people with non-valvular atrial fibrillation.

NICE’s independent Appraisal Committee concluded the convenient drug was more clinically effective than warfarin and resulted in fewer bleeding events.

Trudie Lobban MBE, founder and CEO of the charity Atrial Fibrillation Association, said NICE’s decision is “excellent news for patients” with AF in England and Wales.

Eliquis’ recommendation follows the recent recommendations by the Institute of Xarelto (rivaroxaban) and Pradaxa (dabigatran etexilate) for the same indication.

“Having the choice of effective new treatments which do not require INR monitoring can help reduce the impact that atrial fibrillation has on patients, their families and carers,” said Trudie Lobban.

Final draft guidance states that Eliquis can be considered a treatment option on the NHS in accordance with its licensed indications if informed discussions about the risks and benefits of the drug compared with warfarin, Xarelto and Pradaxa are conducted.

Eliquis, which only received its license for the indication in November 2012, is co-marketed by Bristol-Myers Squibb and Pfizer.

Amadou Diarra, Vice-President, BMS UK and Ireland, said the “fast-tracked recommendation” by NICE highlights the value of the drug as a cost-effective treatment. “We look forward to working with the NHS and other partners to ensure that, where clinically appropriate, patients are provided with rapid access to apixaban, which has been shown to prevent strokes, reduce bleeds and be potentially life-saving compared to the current standard of care, warfarin.”

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 recommended Bayer Healthcare’s convenient Xarelto (rivaroxaban) in final guidance as a treatment option for adults with acute deep vein thrombosis (DVT).

The positive recommendation sees Xarelto become the first non-VKA oral anticoagulant to be recommended for use on the NHS after it impressed in phase III clinical trials.

Professor Carole Longson, NICE Health Technology Evaluation Centre Director, said the treatment is “a potential benefit for many people who have DVT”.

It is estimated there will be more than 46,000 cases of acute DVT in England and Wales this year, with that figure rising to 50,000 within the next four years.

Xarelto is orally administered, enabling patients to avoid the process of regular monitoring through blood tests, dosage adjustments and concerns over diets due to the existing treatment’s interaction with certain food groups.

Dr Gerry Dolan, Consultant Haematologist, Department of Haematology, Nottingham University Hospital, said the guidance provides patients with “an important new therapy choice”.

He added: “Xarelto is proven as an effective agent for DVT treatment which removes some of the challenging constraints of current standard therapy, and can help re-shape and improve anticoagulation services by reducing our reliance on regular coagulation monitoring.”

NICE has changed its original decision on the use of Xarelto (rivaroxaban) as an option for deep vein thrombosis (DVT) and preventing recurrent DVT and pulmonary embolism (PE).

The Institute now recommends Xarelto’s use in final draft guidance after Bayer supplied requested data on the long-term clinical and cost effectiveness of the treatment.

Professor Carole Longson, NICE Health Technology Evaluation Centre Director, said the “additional information and analysis” convinced NICE’s Appraisal Committee.

Earlier this year in March, NICE issued draft guidance that failed to recommend Xarelto after concerns were raised about its use in the context of UK clinical practice.

However, Bayer supplied the requested information on patients who were assigned treatment durations of 3, 6 and 12 months and data on the drug’s cost effectiveness compared to existing options.

As a result, the Committee concluded that Xarelto is more clinically and cost effective than enoxaparin followed by a vitamin K antagonist for preventing recurrent VTE in people in whom treatment for up to 12 months is indicated.

There are believed to be more than 46,000 cases of acute DVT in England and Wales with that figure expected to rise to nearly 50,000 by 2016 due to the ageing population.

Xarelto was recently shortlisted for the globally acclaimed Prix Galien medal.

NICE has recommended Xarelto (rivaroxaban) in final guidance as an option for the prevention of stroke and systemic embolism in people with atrial fibrillation (AF).

The recommendation means patients will get access to the first single tablet, once-daily, oral stroke prevention medicine since the introduction of warfarin in the 1950s

Luis-Felipe Graterol, Medical Director, Bayer HealthCare UK, said the company is “delighted” with NICE’s decision and will now work with local NHS fundraisers to “help evolve services” with Xarelto.

Up to 700,000 people in England and Wales have AF. People with the condition are at a higher risk of developing blood clots and subsequent stroke.

Xarelto is an orally administered drug that helped prevent blood from clotting and has a UK marketing authorisation for the prevention of stroke and system embolism in those with non-valvular AF who have associated risks.

The guidance adds that the decision to swap treatment from warfarin to Xarelto should be discussed between the clinician and patient to highlight any reported risks and benefits.

“We know that some people taking warfarin can find it difficult to maintain their blood clotting at a proper level,” said Professor Carole Longson, NICE Health Technology Evaluation Centre Director. 

“Rivaroxaban, like dabigatran etexilate, which NICE recently approved as an option for this indication, can benefit people with AF. We are therefore pleased to recommend rivaroxaban as another cost-effective option for the prevention of stroke and systemic embolism in people with atrial fibrillation.”

NICE recommended Boehringer Ingelheim’s Pradaxa as a treatment option in final guidance for the same indication back in March.

Bayer HealthCare has published results from the first real-world study of Xarelto (rivaroxaban) which reaffirms the benefits of the once-daily oral anticoagulant in everyday clinical practice.

Findings from the international XAMOS study support the clinical outcomes from the previous RECORD trial which showed Xarelto to have consistently superior efficacy as well as a comparable safety profile to enoxaparin.

Luis Felipe Graterol, Medical Director, Bayer HealthCare UK, says the data delivers “further confidence to prescribers with regards to the clinical potential of Xarelto”.

The drug was recently recommended in final draft guidance by NICE as an option for the prevention of stroke and systemic embolism in people with atrial fibrillation (AF).

The XAMOS study, which included 17,413 patients receiving the treatment or conventional pharmacological treatments for the prevention of blood clots, compared outcomes observed in everyday clinical practice.

The main outcomes of the trial included the incidence of symptomatic thromboembolic events being significantly lower in patients treated with rivaroxaban compared with conventional therapy. Importantly, low and similar rates of major bleeding were also observed.

Dr A.G.G. Turpie, Professor of Medicine, McMaster University, Canada and Chairman of the XAMOS Executive Steering Committee, commented: “As the first and only reported everyday clinical experience of an oral anticoagulant, XAMOS offers real-world evidence that rivaroxaban is effective in protecting against blood clots in the orthopaedic setting.”

Bayer HealthCare has submitted a marketing authorisation application to the EMA to extend the indication of Xarelto (rivaroxaban) to treat pulmonary embolism (PE) and the prevention of recurrent deep vein thrombosis (DVT) and PE in adults.

The application is based on results from the EINSTEIN-PE Phase III study where Xarelto demonstrated efficacy comparable to standard options and significant lower rates of major bleeding.

Dr Kemal Malik, Member of the Bayer HealthCare Executive Committee and Head of Global Development, says the application has the “potential” to extend the benefits of Xarelto “to an even wider patient population”.

If approved by the EMA, Xarelto would become the first oral treatment for the initial treatment of PE and long-term prevention of recurrent DVT.

Xarelto is currently indicated for the VTE prevention in adults following elective hip or knee replacement surgery. It is currently used in more than 100 countries and was recently recommended in final draft guidanceby NICE for the prevention of stroke and systemic embolism in people with atrial fibrillation (AF).

Bayer HealthCare’s Xarelto (rivaroxaban) has been recommended in final draft guidance as an option for the prevention of stroke and systemic embolism in people with atrial fibrillation (AF).

NICE revised its original decision not to recommend the convenient pill after Bayer supplied requested additional evidence on the clinical and cost effectiveness of the medication.

Professor Carole Longson, NICE Health Technology Evaluation Centre Director, said she was “pleased” additional information had been supplied enabling NICE to recommend the treatment.

It is estimated there are currently up to 700,000 people with AF in England and Wales. People with the condition are at a higher risk of developing blood clots and subsequent stroke.

However, the risk of stroke can be reduced by the appropriate use of antithrombotic therapy. Xarelto is the first in a class of drugs known as Factor Xa inhibitors, which act at a critical point in the blood-clotting process to prevent clots forming.

It has a UK marketing authorisation for the prevention of stroke and systemic embolism in patients with non-valvular AF who have one or more risk factors and has been demonstrated in a clinical study to be non-inferior to warfarin, the current standard of care.

Professor John Camm, Professor of Clinical Cardiology at St George’s University of London, welcomed its recommendation. He said: “This news could be particularly important for patients who require long-term or lifelong anticoagulation (for non-valvular AF) who may be seeking a simplified regimen.”

Final guidance is now expected as early as next month.

NICE recently published final guidance recommending the use of Pradaxa (dabigatran) – which recently had its UK price reduced by Boehringer Ingelheim – for the same indication.

NICE has requested more information on the long-term clinical and cost effectiveness of Bayer’s Xarelto (rivaroxaban) for the treatment of deep vein thrombosis (DVT) in draft guidance.

Its independent Appraisal Committee concluded the data supplied did not demonstrate its effectiveness in the context of UK practice and questioned the differences between subgroups using the treatment.

Meindert Boysen, Programme Director Technology Appraisals at NICE, said that Xarelto may be a “useful alternative” to existing options but Bayer needs to supply further data to meet various concerns.

The appraisal is considering the use of Xarelto to treat DVT and prevent recurrent DVT and pulmonary embolism (PE) after acute DVT in adults. It is estimated there will be more than 46,000 cases of acute DVT in England and Wales this year, rising to nearly 50,000 by 2016.

Bayer supplied NICE with information on Xarelto’s cost and clinical effectiveness for patients taking the treatment for up to 12 months.

But the Committee noted that treatment may extend beyond a year and that it wished to explore trial data between subgroups of patients using the treatment for different durations.

“The Committee was concerned that an analysis for patients who required treatment beyond 12 months was not presented, and noted the comments of clinical specialists to the effect that some people with DVT need to continue on anticoagulant therapy permanently,” said Meindert Boysen.

“The Committee also noted subgroup analyses in the main clinical trial that suggested that there could be differences in the effectiveness of rivaroxaban between the groups that were assigned treatment durations of 3, 6 and 12 months that it would wish to explore further.

“The Committee has therefore requested further information from Bayer about the clinical and cost effectiveness of rivaroxaban used as a long-term treatment and has also asked for comment on the differences between the subgroups receiving different intended treatment-durations.”

NICE recommended the use of Xarelto as a treatment option to prevent venous thromboembolism in adults having elective total hip replacement surgery or total knee replacement surgery in 2009.