Pierre Fabre’s Javlor (vinflunine) has not been recommended in final draft guidance for the treatment of bladder cancer after an appeal against an earlier decision failed.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NICE was asked to reconsider an earlier draft guidance which failed to recommend the bladder cancer treatment taking into account the whole population for whom Javlor is licensed.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The final draft guidance is now open for consultation whereby Pierre Fabre again will have the opportunity to appeal the decision.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 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from Roche on its skin cancer drug Zelboraf (vemurafenib) after failing to recommend the treatment for a second time in draft guidance.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Further analysis was requested by NICE during an earlier draft guidance published in June 2012.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 Alimera’s Iluvien (fluocinolone acetonide intravitreal implant) for the treatment of chronic diabetic macular oedema (DMO) in draft guidance.

Its independent Appraisal Committee raised concerns over the economic model submitted by Alimera and the evidence it supplied during the appraisal.

Professor Carole Longson, Health Technology Evaluation Centre Director at NICE, said the Committee “agreed” that the evidence supplied “could not support a positive recommendation”.

Around 336,000 in the UK with diabetes have DMO. Prevalence increases to nearly a third (29%) of people with diabetes who have used insulin for more than 20 years.

DMO occurs as a result of changes in retinal blood vessels. Iluvien is a corticosteroid which has anti-inflammatory and anti-vascular endothelial growth factor (anti-VEGF) properties. By inhabiting VEGT, the implant can decrease the oedema and improve vision.

But NICE concluded economic models “underestimated” the incremental cost-effectiveness ratio for the treatment and that data supplied did not “accurately reflect” current clinical practice.

The draft recommendation is now open to consultation.

NICE has failed to recommend Pharmaxis’ Bronchitol in preliminary draft guidance for the treatment of cystic fibrosis (CF).

Its independent Appraisal Committee raised concerns over “gaps and uncertainties” in the evidence provided by Pharmaxis on the treatment compared with existing options.

Dr Carole Longson, Health Technology Evaluation Centre Director at NICE said the evidence supplied “did not support a positive recommendation”.

Alongside comparative concerns, the Committee also decided the analysis provided by Pharmaxis was not a true reflection of clinical practice or the efficacy of Bronchitol.

CF is one of the UK’s most common life-threatening inherited diseases that affects around 8,000 people.

The treatment, which has a marketing authorisation as an add-on therapy to best standard of care, is conveniently administered by inhalation with an inhaler. It is a proprietary dry powder form of mannitol.

The draft guidance is now open for consultation with a final decision expected in August 2012.

NICE has failed to recommend Roche’s Avastin (bevacizumab) for the first-line treatment of metastatic breast cancer after raising a number of uncertainties over its use in new draft guidance.

Its independent Appraisal Committee questioned the clinical benefit of the drug in overall survival and concluded its high cost was not a good use of NHS resources.

Sir Andrew Dillon, NICE Chief Executive, says the evidence provided “did not conclusively” demonstrate Avastin to be clinically and cost effective.

The breast cancer drug was being appraised when used in combination with the chemotherapy drug Xeloda (capecitabine).

Data provided by Roche had demonstrated that median progression-free survival benefit associated with Avastin plus Xeloda was 2.9 months greater than Xeloda monotherapy alone.

However, the Committee claimed it was unclear whether that benefit translated into an improvement in overall survival.

The Committee also raised the issue of a lack of data showing whether patients would have a better quality of life than if they were treated with chemotherapy alone.

Also, NICE noted that Roche’s cost-effectiveness figures were based on a specific subgroup of patients who had previously received a taxane, and not on the whole capecitabine cohort.

Given these uncertainties the Committee concluded it was not possible to arrive at a plausible Incremental Cost Effectiveness Ratio (ICER) per QALY gained for bevacizumab plus capecitabine compared with capecitabine alone for the whole patient population and were not able to recommend the treatment.

“We can’t recommend a drug that has not been shown to work as well as, or better than, current treatments and costs much more,” said Sir Andrew. “We want to ensure people have access to the best treatments the NHS can afford; bevacizumab has so far not been proven to be clinically or cost-effective.”

Breast cancer is one of the most common cancers in England. In the UK, it is estimated that more than 48,000 women and around 300 men are diagnosed with the disease each year.

The draft guidance is now open for consultation.

NICE has recommended the use of Xgeva (denosumab) in draft guidance for certain cancer patients whose disease has spread to their bones.

The recommendation covers patients with bone metastasis from breast cancer; people with painful bone metastasis from hormone-refractory prostate cancer when treatment has failed; and for those with bone metastasis from other solid tumours for whom zoledronic acid is indicated.

Professor Carole Longson, Director of the Centre for Health Technology Evaluation at NICE, says the condition can have a “major impact on quality of life” and is therefore “pleased” to recommend the treatment.

The guidance stipulates that Xgeva should only be prescribed under the terms of an agreed Patient Access Scheme between Amgen and the DH.

Amgen estimates there are more than 150,000 patients in the UK with solid tumours or bone metastases, of which breast and prostate cancer account for more than 80%.

The spine, pelvis, hip, upper leg bones and skull are most commonly affected by bone metastases with symptoms including pain, and weakening and eventual destruction of the bone.

The majority of patients with the condition are currently treated with bisphosphonates. NICE’s independent Appraisal Committee considered Xgeva as an alternative to standard treatment options where bisphosphonates are not used.

It noted that in clinical trials where Xgeva was directly compared to standard treatment options it improved skeletal-related outcomes. It was also shown to be more clinically effective in patients with breast, prostate and non-small cell lung cancer.

The initial recommendation is now open for consultation.

NICE has requested further details on Bayer HealthCare’s Xarelto (rivaroxaban) in draft recommendation for the prevention of stroke and systemic embolism for those with atrial fibrillation (AF).

Its independent Appraisal Committee concluded that data did not reflect the population in the UK who would be eligible for the treatment and questioned its estimated effectiveness.

Professor Carole Longson, NICE Health Technology Evaluation Centre Director, says Xarelto offers “a significant potential benefit” but NICE is unable to recommend the treatment until additional information address the highlighted issues.

Xarelto has a marketing authorisation in the UK for the prevention of stroke and systemic embolism in patients with non-valvular AF who have one or more risk factors. It is orally administered and helps prevent blood from clotting.

Professor Longson said the importance of “effective antithrombotic therapy” cannot be overestimated however, issues with the information supplied by Bayer prevented a positive recommendation by NICE.

“The Committee concluded that the population included in the single trial presented by the manufacturer as evidence of rivaroxaban’s cost-effectiveness was not reflective of all the people with atrial fibrillation in the UK who would be eligible for treatment with the drug,” she said.

“In particular, the Committee was concerned that the people in the warfarin arm of the trial on average did not achieve as good control of their blood clotting as might be expected in clinical practice in the UK. It was also concerned that the risk of stroke and systemic embolism for the population in the trial was higher than for the overall population eligible for treatment with rivaroxaban.

“The Committee felt that both these factors could mean that the relative effectiveness of rivaroxaban compared with warfarin had been overestimated for the UK population. The Committee is therefore minded not to recommend the drug on the basis of the available evidence pending the receipt of additional information from the manufacturer that will address these issues.”

Roche’s RoActemra (tocilizumab) has been recommended in draft guidance for treating systemic juvenile idiopathic arthritis (JIA).

NICE recommended the treatment after Roche provided its Appraisal Committee with further requested clinical data and it agreed a revised Patient Access Scheme with the DH.

Professor Carole Longson, Health Technology Evaluation Centre Director at NICE, says the recommendation is “good news for children with systemic JIA and those caring for them.”

The draft recommendation is for the use of RoActemra in children aged 2 and over where specific previous treatments have not produced an adequate response.

However, in cases where those whose disease continues to respond to methotrexate or who have not been treated with methotrexate, RoActemra is not recommended as a treatment option.

“The discount agreed as part of the patient access scheme put forward by the manufacturer, in addition to the further information they provided at the Committee’s request, has enabled the Committee to recommend tocilizumab for systemic juvenile idiopathic arthritis in today’s draft guidance,” said Professor Longson.

“The draft guidance proposes that tocilizumab should be the treatment for children aged over 2 years and young people where their systemic JIA hasn’t responded well to other treatments.”

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.

Sanofi’s prostate cancer drug Jevtana (cabazitaxel) has not been recommended by NICE in draft guidance in combination with prednisone or prednisolone as a second line treatment.

NICE’s Appraisal Committee raised concerns about the medication’s cost effectiveness, its associated adverse effects and evidence supplied by the manufacturer.

Sir Andrew Dillon, NICE Chief Executive, says that the Committee was “particularly concerned” about the uncertainty on patients’ renal and cardiac systems.

A number of factors are taken into consideration by NICE’s Appraisal Committees when assessing the cost effectiveness of a treatment. These include the medication’s clinical effectiveness, its side effects, the benefits it brings to patients and the financial cost.

This formula then enables them to determine the cost of using the drug to provide a year of the best quality of life available or quality adjusted life year (QALY). NICE says they usually recommend treatments that cost around £30,000 per QALY or less, however the cost of Jevtana was far greater than this figure.

“The manufacturer of cabazitaxel provided one study on the effectiveness of the drug; in this study cabazitaxel was shown to extend life by approximately 10 weeks,” said Sir Andrew. “Although cabazitaxel has been shown to be effective, it is also associated with a number of adverse events.”

He added that the Appraisal Committee was also concerned about the “validity” of the health related information supplied by Sanofi after it provided one study which demonstrated a median overall survival gain of 2.4 months and an mean overall survival gain of 4.2 in its model.

“The Committee also felt that the treatment did not meet the criteria to be considered under NICE’s special arrangements for end of life, as based on the current data the length of the life extension could not be considered robustly proven to be at least three months,” added the Chief Executive.

“Once all these factors had been taken into account it was estimated that the cost per QALY would be more than £89,000. Therefore the committee concluded that cabazitaxel would not be a cost effective use of limited NHS resources.”

If a drug does meet the criteria to be considered under the Institute’s supplementary advice for end of life treatments, a higher cost per QALY may be accepted by NICE. There is currently no set threshold cost per QALY that meets this criterion, but since the supplementary advice was introduced, the only drug recommended under this method has been Sunitinib for renal cell carcinoma at a cost of £50,000.

NICE said that Javtana did not meet this criterion because the Committee did not consider the length of the life extension to be “sufficiently robust”.