NICE has not recommended Novartis’ Jakavi (ruxolitinib) in final draft guidance for the treatment of disease-related splenomegaly or symptoms in adults with myelofibrosis.

An independent appraisal committee concluded the treatment is clinically effective but raised concerns around the manufacturer’s economic model and many of its assumptions.

Sir Andrew Dillon, NICE Chief Executive, said the regulator had to be sure treatments are clinically and cost effective otherwise “money has to be diverted from elsewhere” to fund such drugs in the NHS.

The guidance states that Jakavi is not recommended for the treatment of disease-related cases of an enlarged spleen or its symptoms in adults with primary myelofibrosis, post polycythaemia vera myelofibrosis or post essential thrombocythaemia myelofibrosis.

Myelofibrosis is a rare type of blood cancer in which the bone marrow produces too many cells too rapidly. This affects the bone marrow making it less able to create cells. Other organs, such as the liver and spleen, then compensate for this by producing additional cells. The spleen, as it begins to create cells, becomes enlarged.

NICE noted that Jakavi was clinically effective in reducing the size of the spleen in these cases and related symptoms. However, it could not be considered a cost-effective option of NHS resources when compared with existing treatments.

The committee found there were “fundamental issues” with the structure of the economic model supplied by Novartis. It concluded that the associated assumptions made increased the uncertainty of the cost-effectiveness ratio (ICER) for the treatment and that rectifying this would actually increase the ICER.

Final guidance is now expected in June 2013.

Cell Therapeutics’ Pixuvri (pixantrone) has not been recommended by NICE in draft guidance as a treatment option for an aggressive form of non-Hodgkin’s lymphoma.

NICE’s independent appraisal committee decided there was insufficient evidence to show the drug works more effectively than existing options and raised question marks over its cost.

Sir Andrew Dillon, NICE Chief Executive, said that clinical trial evidence left NICE with a “number of uncertainties” and questioned how many people may actually benefit from the treatment.

Non-Hodgkin’s lymphoma is the sixth most common cancer in the UK. In 2010, around 12,000 people were diagnosed with the disease. However, Cell Therapeutics estimates that only around 1,650 people with an aggressive form of the disease would be eligible to receive the treatment, if recommended.

Pixuvri has a conditional licence to treat adults with aggressive non-Hodgkin B-cell lymphoma that has either returned after treatment or become resistant to current therapy in those who have received at least two previous types of treatment.

NICE was developing guidance for this specific group of people but was told by clinical experts that the analysis supplied by the manufacturer did not include comprehensive data in patients who had received MabThera (rituximab) – an integral part of first-line treatment and often used in second-line therapy.

Because of this, the committee concluded that differences between previous treatment between the trial population and current practice meant there was considerably uncertainty in determining the treatment’s clinical effectiveness for a UK population.

The recommendation is now open for consultation until 1 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.

NICE draft guidance does not recommend Afinitor (everolimus), a treatment for advanced breast cancer that can increase progression-free survival by four months.

The Novartis drug, described by charity Breakthrough Breast Cancer as “one of the biggest advances in breast cancer treatment in many years”, does not meet NICE’s criteria for an ‘end of life treatment’.

The decision will heighten concern over NICE’s QALY metric for value, which the European Commission recently declared to be scientifically invalid.

Afinitor, an oral formulation of everolimus (which is already widely used as an immunosuppressant), is licensed for use in post-menopausal women with advanced HER-2 negative breast cancer, which will not respond to Herceptin.

The drug inhibits the division of tumour cells and the growth of blood vessels around a tumour, thereby inhibiting tumour growth and metastasis.

Clinical trial results published in September 2012 found that Afinitor could ‘stall’ advanced breast cancer by four to five months.

Dr Rachel Greig of Breakthrough Breast Cancer said: “Everolimus is one of the biggest advances in breast cancer treatment in many years.”

Though “by no means a cure,” she commented, “it could give patients several extra months of good quality of life with their families.”

Sir Andrew Dillon, NICE’s Chief Executive, explained: “While the independent Appraisal Committee acknowledged that everolimus may offer a step change in treatment by restoring sensitivity of the tumour to hormone therapy, the evidence highlighted uncertainty relating to how much the treatment extends overall survival.”

The failure to extend overall survival was only considered crucial because Afinitor did not meet NICE’s criteria for an ‘end of life drug’, since its target patients had a life expectancy slightly over two years.

Consultation on the draft guidance will remain open until 22 April 2013.

Eli Lilly’s Alimta (pemetrexed) has not been recommended in new draft guidance as a maintenance treatment option for non-small-cell lung cancer (NSCLC).

NICE recognised the effectiveness of the treatment but said the potential gain for patients is less than the NHS is being asked to pay for the drug.

A disappointed Sir Andrew Dillon said the Institute can only recommend treatments “which are both clinically and cost effective” for the NHS.

The Institute calculates that the average cost of the treatment is approximately £11,640.

Lung cancer is one of the most common cancers in the UK. NSCLC is the most common type of lung cancer and accounts for around 80% of all cases.

Alimta was being considered as a maintenance treatment option following induction therapy with the drug and cisplatin. It is already recommended as a first line treatment option for NSCLC and as a maintenance treatment option following platinum-based chemotherapy in combination with gemcitabine, paclitaxel or docetaxel.

“Alimta is already recommended as maintenance treatment following a different first line treatment,” said Sir Andrew Dillon. “However, in this case, as maintenance treatment following pemetrexed and cisplatin, although effective, the potential gain for patients is less but the cost to the NHS remains the same.

“It is disappointing not to be able to recommend pemetrexed in our preliminary guidance.”

Roche’s Avastin (bevacizumab) has not been recommended by NHS in draft guidance as a treatment option for advanced ovarian cancer.

Although NICE confirmed the clinical benefits of the treatment it claimed its high cost was too much to justify its use on the NHS.

Sir Andrew Dillon, NICE Chief Executive, said evidence supplied by Roche “did not show that bevacizumab justifies its very high cost and could not be recommended.”

Avastin was analysed as a treatment option in women whose cancer had returned six months or more after initial treatment with platinum-based chemotherapy.

Ovarian cancer is among the top five most common cancers in women in the UK. In 2010, there were more than 7,000 new cases diagnosed.

NICE’s Appraisal Committee found Avastin may help the delay of cancer in patients for a limited time. But determined its cost was too much to expect the NHS to pay.

“We understand there are limited treatment options available to women with recurrent advanced ovarian cancer and it is always disappointing when we are not able to recommend a treatment,” said Sir Andrew. “However, it is important to remember that there are other treatments already available in the NHS for treating this condition.”

Pierre-Fabre’s Javlor (vinflunine) has not been recommended for the treatment of advanced or metastatic transitional cell carcinoma of the urothelial tract by NICE in final guidance.

The bladder cancer drug was not recommended in final draft guidance published last year but manufacturer Pierre-Fabre submitted updated evidence to try and reverse that decision.

However, Sir Andrew Dillon, NICE Chief Executive, said the fresh evidence was inconclusive.

“The manufacturer has been unable to provide the Appraisal Committee with conclusive evidence on how effective vinflunine is, particularly the extent to which it can prolong survival compared with best supportive care,” he said.

“When we recommend the use of expensive treatments designed to extend life, we need to be confident about the nature and the extent of the benefit they bring.”

Despite the guidance, cancer patients currently receiving Javlor have the option to continue using the treatment until they and their clinicians consider it appropriate to stop.

NICE has not recommended the use of Alimera Sciences’ implant Iluvien (fluocinolone acetonide intravitreal) for the treatment of chronic diabetic macular oedema (DMO).

The Institute’s Appraisal Committee analysed data supplied by Alimera but raised concerns over a number of uncertainties.

Sir Andrew Dillon, NICE Chief Executive, said the information supplied did not show the benefits to patients to “justify the price the NHS is being asked to pay.”

Alimera Sciences submitted additional information following draft guidance, which was published by NICE in August.

But the updated data failed to impress NICE’s Appraisal Committee who questioned the implant’s clinical effectiveness, its negative side effects and how Alimera had judged Iluvien’s use in current clinical practice.

“When NICE recommends any drug or treatment, we have to be sure that it is both clinically and cost effective, because money has to be diverted from elsewhere in the health service to pay for it,” said Sir Andrew Dillon.

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.