Final draft guidance from NICE recommends Xarelto (rivaroxaban) to treat pulmonary embolism (PE) and deep vein thrombosis (DVT) and prevent their recurrence.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

NICE has failed to recommend Pfizer’s Xalkori (crizotinib) for previously treated anaplastic-lymphoma-kinase-positive advanced non-small-cell lung cancer in new draft guidance.

An independent Appraisal Committee decided the drug did not meet NICE’s end-of-life treatment criteria so its cost exceeded the limit deemed cost-effective for NHS use.

Sir Andrew Dillon, NICE Chief Executive, said that although the clinical benefits of Xalkori had been recognised the high cost of the drug meant it could not be considered as a treatment option.

NICE usually recommends clinically effective treatments that cost up to at a maximum of up to £30,000 per quality adjusted life year (QALY) – the methodology current used to assess value.

If certain treatments meet the criteria to be considered under NICE’s supplementary advice for end-of-life treatments a higher cost per QALY may be accepted. The highest cost per QALY NICE has recommended has been around £50,000.

However, NICE’s Appraisal Committee concluded that the most plausible cost per QALY for Xalkori would be somewhere between £63,800 and £181,100 when compared with existing treatments and between £51,700 and £80,500 when compared with best supportive care.

“We have already recommended a number of treatments for the various stages of non-small-cell lung cancer,” said Sir Andrew Dillon. “However, although the independent committee that considered the evidence found crizotinib to be clinically effective treatment for ALK-positive non-small-cell lung cancer, even if the supplementary advice to the Committee for life-extending treatments had applied, crizotinib could not be considered a cost-effective use of NHS.”

NICE’s guidance is now open for consultation.

New draft NICE guidance recommends giving tamoxifen or Evista (raloxifene) to women with a family history of breast cancer as a preventative drug.

The provisional guidance update makes new suggestions for genetic testing, screening and preventative treatment in women at high risk of breast cancer.

If confirmed by NICE, the recommendations would mean the first use of a drug by the NHS to prevent breast cancer.

Breast cancer is diagnosed in 50,000 women in the UK each year. Women with a sister and a mother or aunt who have developed breast cancer before the age of 50 are considered at high risk of developing the disease for genetic reasons.

Breast cancer is also likely to occur earlier, and to be harder to treat, in this patient class, who are fewer than 1% of women aged under 30.

Genetic testing can identify either of two mutant genes that are linked to increased risk of breast cancer, as well as ovarian cancer.

NICE emphasises the need to reduce the incidence of breast cancer in high-risk women. It estimates that for every 1000 women treated with tamoxifen or Evista for a five-year period, there would be 20 fewer cases of breast cancer.

However, the drugs have side-effects including increased risk of blood clots, so their preventative use would need to be carefully considered.

Tamoxifen was developed by AstraZeneca but has long been off patent. Lilly’s Evista came off patent more recently. Neither drug has UK marketing authorisation for prevention of breast cancer.

Chris Askew, Chief Executive of the charity Breakthrough Breast Cancer, said the draft guidance was “a historic step for the prevention of breast cancer”.

NICE has recommended the use of GSK’s Revolade (eltrombopag) in draft guidance for treating chronic immune (idiopathic) thrombocytopenic purpurai (ITP).

Original guidance, published in October 2010, was reviewed by NICE after GSK agreed a Patient Access Scheme with the DH to supply the treatment at a discounted rate.

The guidance now recommends Revolade in adults who have had their spleen removed and whose condition is refractory to other treatments and as a second-line treatment in patients who have not had their spleen removed due to surgery being contraindicated.

ITP is a bleeding disorder caused by abnormally low levels of platelets in the blood. It is estimated there are around 3,000-3,500 cases in the UK.

Revolade increases platelet production through activation of the thrombopoietin receptor. By stimulating production, the drug helps to reduce bleeding.

“People living with ITP are at daily risk of bleeding and subsequent bruising, and this can have a detrimental effect on quality of life,” said Dr Carole Longson, Health Technology Evaluation Centre Director at NICE. “NICE is, therefore, pleased to be able to recommend eltrombopag for this condition.”

Final guidance is now expected to be published in May 2013.

NICE has failed to recommend the use of Roche’s Avastin (bevacizumab) as a treatment option for advanced ovarian cancer in draft guidance.

The Institute’s independent Appraisal Committee concluded the drug was not a cost-effective option for the NHS after analysing data from two separate studies.

Sir Andrew Dillon, NICE Chief Executive, said Roche provided “no evidence to show that the clinical benefit of the treatment justifies its cost, when compared to existing treatments”.

The appraisal considered whether Avastin should be recommended when used with paclitaxel and carboplatin in women with advanced forms of the disease.

NICE analysed evidence from clinical trials from the licensed dosage of Avastin and the lower dosage, which is routinely prescribed in UK clinical practice.

Avastin, in combination with paclitaxel and carboplatin, was found, in certain cases, to delay the spread of cancer but NICE added there were concerns over “inconsistencies” in the data supplied by Roche.

“Although it was acknowledged that Avastin, when used in combination with paclitaxel and carboplatin, appears to provides benefit to some patients by delaying the spread of their cancer, it was unclear whether this translated into an overall survival benefit,” said Sir Andrew Dillon.

Pfizer’s treatment of advanced kidney cancer Inlyta (axitinib) has not been recommended in draft guidance.

NICE’s independent Appraisal Committee questioned the trial data supplied by Pfizer and were left concerned about the drug’s validity and reliability.

Sir Andrew Dillon, NICE Chief Executive, said the Institute will not “divert NHS funds to a treatment that costs more but doesn’t help people live longer.”

The appraisal considered the use of Inlyta for the treatment of advanced renal cell carcinoma after failure of prior treatment with sunitinib or a cytokine.

However, experts told the Appraisal Committee that the use of cytokines in clinical practice is declining with only a handful of patients currently using the treatments. NICE was informed that the majority of patients are now being treated with sunitinib or pazopanib – both recommended by NICE.

Pfizer supplied NICE with trial data comparing Inlyta to sofafenib, a drug not recommended by NICE and not identified in the scope. “The trial also lacked a comparison to ‘best supportive care’, which is what the majority of patients receive at the moment; therefore an ‘indirect’ and ‘simulated’ comparison was made using separate data from another trial,” Sir Andrew Dillon said.

The recommendation is now open for consultation. Pfizer has also been invited to comment on the evidence it supplied as part of the appraisal.

NICE has failed to recommend InterMune’s Esbriet (pirfenidone) as a treatment option on the NHS for people who have idiopathic pulmonary fibrosis in draft guidance.

Questions were raised by NICE’s independent Appraisal Committee over the cost-effectiveness and the long-term clinical benefits of the treatment.

Professor Carole Longson, Director of the Centre for Health Technology Evaluation at NICE, said that although the Committee is aware of Esbriet’s benefits “it was uncertain whether this benefit persisted over time because the clinical trials were short in duration.”

The recommendation is now open for consultation. Final guidance is expected in April 2013, after NICE’s committee reviews any responses on the decision in January.

Esbriet has a UK marketing authorisation for the treatment of mild-to-moderate idiopathic pulmonary fibrosis in adults. The condition is a progressive disease associated with scarring of the lung, which makes breathing difficult. There are around 4,000 adults diagnosed each year in the UK.

“It was unclear whether the drug could improve overall survival for people with the disease because of uncertainty about the correct classification of deaths in the clinical trials as being related to idiopathic pulmonary fibrosis or not, a low number of deaths in both treatment and placebo arms and short follow-up,” said Professor Longson.

“Given these uncertainties and when compared with best supportive care, our committee concluded that treatment with pirfenidone would not represent a cost-effective treatment option for the NHS.”

NICE has failed to recommend Xolair (omalizumab) for the treatment of severe persistent allergic asthma in adults and children in draft guidance after reviewing new evidence.

The guidance reviewed two separate appraisals in 2007 – one which recommended Xolair for adults and one which did not for use in children.

Sir Andrew Dillon, Chief Executive of NICE, said that new data showed that the treatment is “not as clinically or cost-effective as was first thought.”

Xolair has a UK marketing authorisation as an add-on therapy to standard care to improve control of asthma in adults and youngsters aged 6 and above with severe persistent allergic asthma.

However, after new evidence was made available, particularly on mortality data, NICE’s independent Appraisal Committee decided that the draft guidance should not recommend the treatment for either children or adults.

In addition, the Committee also took into account changes to the dosing schedule and the effect this would have on the cost effectiveness of the treatment. This, when combined with uncertainties over the new clinical data, did not support a positive recommendation.

The Committee did recognise that Xolair was an effective therapy for asthma sufferers but said evidence submitted as part of the appraisal included people whose condition was less severe than those currently being treated in the UK.

“The Committee is aware that severe, persistent allergic asthma can have a detrimental effect on a person’s life and that omalizumab is an effective therapy for children, adolescents and adults with severe persistent allergic asthma,” said Sir Andrew Dillon.

“Unfortunately, the Committee was unable to continue to recommend omalizumab for use in the NHS.”

Patients currently taking Xolair should be able to continue treatment until their clinician considers it appropriate to stop.

Final guidance is now expected in April 2013.

Pierre Fabre’s Javlor (vinflunine) has not been recommended in final draft guidance for the treatment of bladder cancer after an appeal against an earlier decision failed.

Additional evidence supplied by Pierre Fabre failed to convince NICE’s independent Appraisal Committee that the treatment was either cost- or clinically-effective.

Sir Andrew Dillon, NICE Chief Executive, said Pierre Fabre failed to provide “conclusive evidence” on how effective the treatment is on prolonging survival with best supportive care.

NICE was asked to reconsider an earlier draft guidance which failed to recommend the bladder cancer treatment taking into account the whole population for whom Javlor is licensed. The appeal focused on the comparator treatment originally outlined in the scope.

Pierre Fabre estimates that around 800-1500 patients would be eligible to receive the treatment according to its licence. However, the Appraisal Committee raised uncertainties around the extent to which Javlor extends life for patients with transitional cell carcinoma and highlighted its expensive price tag.

The final draft guidance is now open for consultation whereby Pierre Fabre again will have the opportunity to appeal the decision.

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.