NICE has failed to recommend the use of Sanofi’s Jevtana (cabazitaxel) in final guidance in combination with prednisone or prednisolone as a second line treatment for prostate cancer.

Concerns were raised by NICE’s Appraisal Committee over the cost of the treatment and its side-effects, including haematological adverse events and diarrhoea.

Sir Andrew Dillon, Chief Executive of NICE, said the Committee queried the “nature of the health-related quality of life information” provided by Sanofi.

Sanofi had appealed the decision not to recommend the treatment however, this was dismissed on all points.

NICE recognised that Jevtana resulted in a mean improvement of greater than three months in mean overall survival. But the Committee considered that its cost per QALY gained would exceed £87,500 – considerably higher than the most expensive treatment it has recommended at £50,000.

Additionally, the numerous side-effects, such as fatigue, nausea, vomiting and constipation, associated with Jevtana raised concerns with the Appraisal Committee.

“We need to be sure that new treatments provide sufficient benefits to patients to justify the significant resources the NHS would need to make available,” said Sir Andrew.

“Although cabazitaxel can extend life for some patients, its price remains well above what the independent Committee appraising this drug considered acceptable, given the benefits it offers.”

An increase in sales at the ‘new Genzyme’ helped Sanofi’s business EPS grow by 7.2% as revenue topped €8.5bn in the first three months of 2012.

Sales of growth platforms, which include Genzyme, were €5.38bn and accounted for 63.2% of total sales, up from 59.2% in Q1 2011, despite global generic competition on Plavix and Aprovel.

Christopher Viehbacher, Sanofi CEO, said the “strong performance” in the first quarter was “driven by Genzyme, our growth platforms, and cost savings”.

However, Sanofi still expects profits to be down by around 12% to 15% on last year’s figures as a result of generic exposure of major brands.

Overall sales were up 7% compared to the same period last year after revenue in emerging markets increased by nearly a tenth (9.9%), and its pharmaceuticals division was boosted by increased sales in its diabetes and oncology businesses.

First quarter sales in pharmaceuticals reached €7.3bn, an increase of 8.8%, driven by the performance of diabetes drug Lantus which saw sales rise 17.2% to €1.1bn. But generic competition on Plavix, Lovenox and Taxotere hit sales, despite increased demand for Apidra, Eloxatin and Jevtana.

The ‘new Genzyme’ recorded sales of €400m in Q1 – up by 13.7%. Sales of Fabrazyme were up by half to €47m, with Cerezyme up by 5.8% to €149m and sales of Myozyme/Lumizyme also increasing by 17% to €112m.

Sanofi’s own generics business generated an increase of sales after the recent launch of the authorised generic Lovenox saw revenue grow by 6.5% to €439m.

Vaccine sales were down slightly (0.2%) to €617m after the delayed timing of supply of flu vaccines in the Southern Hemisphere. However, the news was better for Sanofi’s consumer health division as it achieved record sales of €805m.

NICE has failed to recommend Sanofi’s Jevtana (cabazitaxel) as a second-line treatment in combination with prednisone or prednisolone for prostate cancer in final draft guidance.

Concerns were raised by the Appraisal Committee over the various side-effects of the treatment, especially haematological adverse events and diarrhoea, and the information supplied by Sanofi.

Sir Andrew Dillon, NICE Chief Executive, says the Committee concluded the treatment did not provide “enough health benefit to justify its cost”.

The Committee found that the use of Jevtana resulted in a mean improvement of more than three months in mean overall survival. The drug also met the criteria used be considered under NICE’s end of life considerations.

Each cycle of treatment with Jevtana costs approximately £3,700 and would cost around a median of £22,000 per patient.

However, NICE considered that the additional weight needed to bring the Incremental Cost Effective Ratio (ICER), that is usually considered a cost-effective use of NHS resources, was too high. It calculated that the most plausible ICER would be above £87,500 per QALY gained for the treatment. The highest cost per QALY of a recommended drug has been £50,000.

Alongside the major concerns of the side-effects of haematological adverse events and diarrhoea, NICE also found patients suffered from fatigue, nausea, vomiting, constipation, asthenia, haematuria, back pain, anorexia, pyrexia, dyspnoea, abdominal pain, dysgeusia, cough, arthralgia, and alopecia.

“We need to be sure that new treatments provide sufficient benefits to patients to justify the significant resources the NHS would need to make available,” said Sir Andrew Dillon. “Although cabazitaxel has been shown to be effective in extending life, it is also associated with a number of side effects.”

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”.

Sanofi’s Jevtana (cabazitaxel) has become the first advanced prostate cancer drug to be launched in the UK after its approval by the EMA in March.

The drug is licensed for men with metastatic hormone-refractory prostate cancer (mHRPC), in combination with prednisone, whose cancer has progressed despite treatment with standard chemotherapy.

Debasish Roychowdhury, Senior Vice President and Head, Global Oncology Division of Sanofi said after its European approval that “Jevtana offers new hope for patients”.

The EMA’s approval of Jevtana was based on Phase III results from the TOPIC trial. Results showed the cancer drug significantly extended overall survival in men with mHRPC by nearly 2.5 months.

Jevtana was also shown to double the median time before the disease progressed, compared with chemotherapy drug mitoxantrone.

It could soon be joined on the UK market by Provenge. US biotech firm Dendreon is currently planning to file its highly novel cancer vaccine, also for mHRPC, in Europe later this year.

It received FDA approval last year after its pivotal Phase III IMPACT trial showed the drug extended median survival by 4.1 months and also reduced the risk of death more by more than a fifth (22.5%).

Sanofi-aventis has launched Jevtana in the UK for the treatment of men with metastatic Hormone Refractory Prostate Cancer (mHRPC).

The drug is indicated in combination with prednisone/prednisolone for mHRPC patients who have previously been treated with docetaxel.

It is the first licensed agent to significantly extend overall survival in men with mHRPC whose disease has progressed during or after treatment containing docetaxel.

In trials, patients receiving Jevtana had a median overall survival of 15.1 months, compared to 12.7 months for those in the control arm of the study. The drug was also shown to double the median time before the disease progressed compared with mitoxantrone – 2.8 months versus 1.4 months.

The European Commission issued a marketing authorisation for Jevtana in March 2011 based on these trial results.

As a semi-synthetic taxane, Jevtana can overcome treatment resistance to the

taxanes docetaxel and paclitaxel. It works by attacking the microtubular structure of cancer cells to inhibit cell division and cause cancer cell death.