NICE has recommended Novartis’ Tasigna (nilotinib) and Glivec (imatinib) for the first line treatment of chronic myeloid leukaemia (CML), but failed to recommend BMS’ Sprycel (dasatinib) in final guidance.

Despite evidence demonstrating Sprycel and Tasigna to be more clinically effective than standard dose Glivec, Sprycel’s cost swayed NICE’s decision after Novartis agreed to supply Tasigna at a reduced price.

Professor Carole Longson, Director of the Centre for Health Technology Evaluation at NICE, says the cost reduction “enabled” the independent Appraisal Committee to recommend its use on the NHS.

The appraisal incorporates a partial review of guidance published in October 2003 which recommended standard dose Glivec for first line treatment of CML.

NICE’s independent Appraisal Committee considered results of clinical trials that showed statistically more people receiving Sprycel and Glivec had a complete cytogenetic response and a major molecular response compared with people using Glivec after a 12 month review.

The Committee also noted the opinions of clinical specialists and patient experts who suggested that Tasigna and Sprycel were more effective than standard dose Glivec – despite it being a “very effective” option for the majority of patients.

Sprycel and Tasigna both cost more than £30,000 per patient, per year. Standard dose Glivec costs in the region of £20,000. However, after Novartis had agreed a Patient Access Scheme with the Department of Health for Tasigna, NICE deemed it was a cost effective use of NHS resources.

“The recommendations reaffirm the use of imatinib as an effective treatment for the majority of patients and a cost effective use of NHS resources, and we are also very pleased to be able to add a further treatment option for these patients by recommending nilotinib,” said Professor Longson.

“Although no trials directly comparing dasatinib and nilotinib were available, the committee concluded from indirect comparisons that dasatinib and nilotinib could be considered equally as effective in treating CML.

“However, the manufacturer of nilotinib has already agreed with the Department of Health to provide the drug to the NHS at a discounted price.”

CML is a rare condition that affects around 560 people in the UK each year.

Novartis has reported an 18% drop in its profits for the first quarter of 2012, due to generic competition and manufacturing problems.

The Swiss company’s net profit fell to $2.33bn from $2.82bn in the same period last year, while its sales revenue fell by 2%.

“We expected a challenging quarter in Q1, and we delivered in line with our expectations,” said Novartis CEO Joe Jiminez.

He highlighted the impact of the temporary closure of the company’s factory in Nebraska, USA, which cost Novartis £200m in quarter 1.

Novartis’ generics business suffered from further production problems, which combined with growing competition to reduce its sales by 10%.

Jimenez said the company would restart production at its Nebraska site, but expected its full-year profits to be below the 2011 figure.

However, he said that Novartis expected sales of over $1bn this year from its nine leading drugs, including Galvus (for diabetes), Tasigna (for leukaemia) and Lucentis (for wet AMD).

In addition, he said, the company’s oral MS drug Gilenya was set to achieve ‘blockbuster’ status, despite safety concerns that have led to label changes.

NICE has recommended the use of Tasigna (nilotinib) and Glivec (imatinib) for the first-line treatment of chronic myeloid leukaemia (CML), but failed to recommend Sprycel (dasatinib) in final draft guidance.

The guidance reaffirms the use of standard dose Glivec and recommends the use of Tasigna after Novartis agreed a Patient Access Scheme with the DH to lower its cost.

Sir Andrew Dillon, NICE Chief Executive, says the Institute is “very pleased to be able to add a further treatment option” for patients.

CML is a rare condition that affects around 560 people in the UK each year.

NICE’s independent Appraisal Committee considered the results of clinical trials and noted the views of clinical specialists and patient experts when conducting the appraisal.

It found that more patients receiving Tasigna and Sprycel had a complete cytogenetic response and a major molecular response than people receiving Glivec at 12-month follow-up.

Also, experts said that Tasigna and Sprycel are more effective than standard-dose Glivece with a theoretically superior mechanism of action, although this option remains very effective.

The Committee concluded that available evidence suggests Tasigna and Sprycel provide superior clinical benefit as measured by surrogate outcome measures to standard-dose Glivec in people with chronic phase CML – despite no direct head-to-head data being available.

“Although no trials directly comparing dasatinib and nilotinib were available, the Committee concluded from indirect comparisons that dasatinib and nilotinib could be considered equally as effective in treating CML,” said Sir Andrew Dillon.

“However, the Department of Health and the manufacturer of nilotinib have already agreed to provide the drug to the NHS at a discounted price. This reduction in cost enabled the independent Committee to approve nilotinib for use on the NHS.”

Oral cancer drugs such as Glivec and Tarceva are negatively affected by other medications including steroids and antibiotics, according to a new US study.

The Medco Research Institute (MRI) has claimed that medications taken by as many as 75% of cancer patients interfere with the effects of oral kinase inhibitors, a major class of adjunctive cancer therapy.

The effect of the medication interference is to weaken the effectiveness of the anti-cancer treatment and/or increase its toxicity, the study found.

Oral kinase inhibitors, which suppress tumour cell metabolism, are widely prescribed for their ability to increase the effectiveness (and reduce effective dosage levels) of chemotherapy.

The MRI study, which looked at 4,617 cancer patients, found that 23–74% of them were being prescribed a medication that interfered with their oral cancer drug. Of these, 43% showed a reduction in the efficacy of the cancer drug and 68% showed an increase in its toxicity.

Oral kinase inhibitors include (UK trade names): Glivec (imatinib), Tarceva (erlotinib), Sprycel (dasatinib), Afinitor (everolimus), Tyverb (lapatinib), Tasigna (nilotinib), Votrient (pazopanib), Nexavar (sorafenib) and Sutent (sunitinib).

The medications that interfere with them, according to the study, are calcium channel blockers, antifungal agents, steroids, proton pump inhibitors and some antibiotics.

Dr Steve Bowlin, Senior Director at the MRI and co-author of the study, said: “Since these are drugs launched in the past decade for fairly small patient populations, we are learning more about how they are used in real-world settings as compared to traditional clinical trials that test safety and efficacy in a tightly-controlled environment.

“Oncologists are not always aware of other medications prescribed by other doctors and vice-versa, which can pose a real hazard for their patients on oral cancer therapies.”

NICE has recommended Novartis’ Tasigna (nilotinib) for the treatment of chronic myeloid leukaemia (CML) but failed to recommend Sprycel (dasatinib) and high dose Glivec (imatinib) in final guidance.

The Appraisal Committee concluded all three treatments provided clinical benefit for people with Glivec-resistant CML but opted for Tasigna when provided under the terms of a patient access scheme.

Professor Carole Longson, Health Technology Evaluation Centre Director at NICE, says that although Tasigna is “expensive” the discount enabled the Committee to approve its use.

NICE estimates that Tasigna costs more than £30,000 per patient, per year.

The Institute received two appeals on its final draft guidance not to recommend Bristol-Myers Squibb’s Sprycel and Novartis’ Glivec, but both of these were dismissed on all accounts.

When completing the FAD, it found that patients with Glivec intolerance generally had a higher response rate to Tasigna and Sprycel than those with Glivec-resistant CML. But a lack of evidence base meant the magnitude of the benefit was uncertain.

When considering the updated analysis submitted during consultation on the first draft from Novartis, the Committee concluded that the ICER of £22,800 per QALY gained for Tasigna compared with hydroxycarbamide was optimistic. But, when provided at a discounted rate, it was regarded as a cost-effective use of NHS resources.

However, the ICER for Sprycel compared with hydroxycarbamide would be more than £43,800 and could rise further. The Committee also noted that high-dose Glivec was more expensive and less effective than the other treatments under evaluation.

“We are very pleased to be able to recommend nilotinib as a treatment option for the chronic and accelerated phases in people who are resistant or intolerant to standard dose imatinib,” said Professor Longson.

CML is a very rare condition that affects around 560 in the UK each year. If treatment with Glivec does not work, current options include interferon-alfa, hydroxycarbamide or a bone marrow transplant.

NICE has recommended the use of Novartis’ Tasigna (nilotinib) and Glivec (imatinib) for the first-line treatment of chronic myeloid leukaemia (CML) but not recommended Bristol-Myers Squibb’s Sprycel (dasatinib).

In new draft guidance, NICE reaffirms the use of Glivec as a cost effective option and Tasigna after Novartis agreed a Patient Access Scheme with the DH, but deemed Sprycel to be too expensive.

Sir Andrew Dillon, NICE Chief Executive, says the Institute is “very pleased to be able to add a further treatment option” for patients with the rare condition.

The appraisal incorporates a partial review of 2003 guidance which recommended standard-dose Glivec for the first-line treatment for CML. High-dose Glivec was only recommended in the context of clinical trials.

Tasigna and Sprycel both cost more than £30,000 per patient, per year, NICE calculates. Standard dose Glivec costs £20,000. The discount price between Novartis and the DH for Tasigna has been kept confidential.

NICE is also currently appraising the use of Sprycel, high-dose Glivec and Tasigna for the treatment of Glivec-resistant CML and Sprycel and Tasigna for those with CML for whom treatment with Glivec has failed due to intolerance.

CML affects around 560 people in the UK each year.

Sanofi is expected to overthrow Pfizer’s nine-year reign as the world’s biggest drug maker, according to new research.

The French pharmaceutical company is expected to retain the top spot until at least 2016, with Pfizer falling to third place behind Novartis due to the loss of Lipitor’s US patent protection, according to EvaluatePharma (see figure one).

The report says that Sanofi’s numerous acquisitions over the last decade have contributed largely to the company’s success, gaining $20 billion after it bought out Genzyme.

Sanofi’s mergers over the last decade have contributed a great deal to its current position, starting with its $30 billion deal with Synthélabo in 1999.

It is expected that the company will retain its top position until at least 2016, mainly thanks to sales of enzyme replacement therapies through its acquisition of Genzyme.

Also, the company’s addition of Cerezyme and Myozyme blockbuster drugs will help fill the gap left by Lovenox, Taxotere, and Plavix, which loses US patent protection in 2012.

Pfizer’s $68 billion buyout of Wyeth in 2009 helped fill the gap left by Lipitor, but it will be difficult to replace the drug’s global sales figure of $13.4 billion seen in 2008, which set the record as the biggest selling medicine.

Following its loss of US patent protection in November 2011, Lipitor sales are estimated to shrink to $2 billion by 2016.

However, pipeline products such as rheumatoid arthritis (RA) pills tofacitinib and Eliquis are expected to boost Pfizer’s drug sales after 2016, which will help retain the company’s position in the top-five pharmaceutical companies.

Merck’s four-year outlook is seen as bleak despite its takeover of Schering-Plough for $41 billion in 2009, with only 1% annual sales growth predicted, conceding to European companies GlaxoSmithKline and Roche to overtake the company.

EvaluatePharma predicts that Johnson & Johnson’s recent pipeline successes will benefit the company in the coming years, despite its drugs arm being substantially smaller than the five biggest pharma companies.

It is thought that Novartis will be Sanofi’s closest competition over the next few years, with strong sales growth from Gilenya and Tasigna due to Diovan’s loss of patent protection next year.

Figure 1:

NICE has recommended a discounted version of Tasigna (nilotinib, pictured) for the treatment of chronic and accelerated phases of chronic myeloid leukaemia (CML) that is resistant or intolerant to standard dose Glivec, in new draft guidance.

But the Institute has failed to recommend Sprycel (dasatinib) despite saying it is equally as effective as Tasigna, and high-dose Glivec for the same condition.

Professor Carole Longson, Health Technology Evaluation Centre Director at NICE, says that both treatments are “expensive” but Novartis’ discount “enabled the independent Committee to approve” its use on the NHS.

Both Tasigna and Sprycel cost over £30,000 per patient, per year. Novartis recently increased the price to high-dose Glivec to £40,000 per patient, per year, although it requested to keep discounted price of Tasigna confidential.

CML is a very rare condition that affects approximately 560 people each year in the UK. If the standard treatment option Glivec does not work, current recommended alternatives are are interferon-alfa, hydroxycarbamide, or a bone marrow transplant.

“We are very pleased to be able to recommend nilotinib as a treatment option for the chronic and accelerated phases of this condition,” said Professor Longson.

NICE has failed to recommend Sprycel (dasatinib), Tasigna (nilotinib) or high-dose Glivec (imatinib) for the treatment of chronic myeloid leukaemia (CML) in draft guidance.

The Institute pointed towards the £30,000 cost of Sprycel and Tasigna and the recently increased charge of £40,000 per year for 800mg Glivec as a factor in making its decision.

Sir Andrew Dillon, NICE Chief Executive, says the evidence for the effectiveness of the three is “very weak” and they must be confident when recommending “very expensive treatments”.

The appraisal of the trio for the treatment of CML that is resistant to standard-dose Glivec is one of three currently being conducted by NICE.

CML is a very rare condition that affects approximately 560 people in the UK each year. It is a chronic condition, meaning the drugs would be used for a prolonged period of time.

NICE says that neither Bristol-Myers Squibb, the manufacturer of Sprycel and Tasigna, nor Novartis, who produces Glivec, submitted a patient access scheme to the DH to help reduce long-term costs.

Consultation on the guidance will now be considered next month with the next draft guidance to follow.

Novartis’ Tasigna (nilotinib) has been launched in the UK for adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukaemia (Ph+ CML).

The UK launch in this indication follows recent EMA approval earlier this month. Tasigna was previously available in the UK for use in imatinib intolerant and/or resistant patients.

The drug received EU approval based on evidence of its superiority to the current standard of care, Glivec (imatinib).

The company is optimistic that this evidence will make Glivec the new “treatment of choice” in the UK.

A recent 24-month trial demonstrated that less than 1% of patients progressed to the accelerated phase or blast crisis phases on Tasigna 300mg twice-daily, compared to 4.2% on imatinib 400mg once-daily.

The data also showed that more than double the number of patients taking Tasigna 300mg twice daily achieved Complete Molecular Response (CMR) compared to those receiving imatinib.

Professor Richard Clark, Consultant Haematologist at Royal Liverpool University Hospital and one of the principal investigators involved in the study, said: “Nilotinib has the potential to stabilise the disease and therefore become the new standard of care for patients with newly diagnosed chronic phase Ph+ CML.

“In particular, the prevention of disease progression is a dramatic achievement, which could improve long term survival, a goal for everyone diagnosed with life-threatening conditions like CML.”