Multiple sclerosis (MS) treatment Gilenya (fingolimod) has had its prescribing information updated after discussions with the EMA and the FDA.

Novartis has agreed to the updates to provide healthcare professionals with further guidance on initiating its use in patients with MS after reviews by both health regulators following cardiovascular concerns in certain patients.

Patients starting the use of Gilenya should have an electrocardiogram (ECG) and blood pressure measurement prior to the first dose with regular updates and continuous ECG monitoring for a minimum of six hours afterwards.

The CHMP has now confirmed a positive benefit-risk profile for the once-daily oral medication following the label change.

“We believe that Gilenya is a valuable treatment option for many patients with relapsing-remitting MS, and we welcome the confirmation of the positive benefit-risk profile of the drug which also supports our continued belief of the blockbuster potential of Gilenya,” said David Epstein, Division Head of Novartis Pharmaceuticals.

In additional, the label update in the EU also cautions against Gilenya’s use in patients who may be less tolerant of it or are more likely to develop a significantly slowed or abnormal heart rate because of certain underlying conditions or concomitant medications.

In the EU, Gileyna is approved for people with highly active relapsing-remitting MS despite treatment with beta interferon, or in patients with rapidly evolving severe relapsing-remitting MS.

The CHMP’s labelling recommendations will be reviewed by the European Commission with a final decision expected in June 2012.

Novartis will revise the product information for its hypertension drug Rasilez (aliskiren) to take account of new European Medicines Agency (EMA) drug interaction warnings.

A risk-benefit review from the EMA’s Committee for Medicinal Products for Human Use (CHMP) concluded that aliskiren-containing medicines may interact harmfully with ACE inhibitors or ARBs.

The CHMP review followed Novartis’ decision in December 2011 to abandon the ALTITUDE trial of Rasilez used in combination with those medications.

While confirming that Rasilez is suitable for the treatment of essential hypertension (where no external risk factors present), the CHMP requested two changes in the product information in the EU:

• A contraindication against its use with an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) in patients with diabetes and/or moderate to severe renal impairment.

• A warning against its use in any patients who are taking an ACE inhibitor or an ARB, asking the doctor to assess the balance of risk and benefit carefully.

Novartis will inform doctors in the EU of these changes, which will also affect combination products containing aliskiren such as Rasilamlo and Rasitrio.

David Epstein, Division Head of Novartis Pharmaceuticals, commented: “Patient safety continues to be the highest priority for Novartis, and we are working closely with the CHMP, EMA and other health authorities worldwide to continue to provide Rasilez and combination products containing aliskiren to the most appropriate patient population who would benefit.”

The ALTITUDE study was a large-scale trial of Rasilez used in combination with an ACE inhibitor or ARB in a specific population of patients with type 2 diabetes and renal impairment to reduce the risk of cardiovascular and renal events.

Novartis halted the trial in December after the Data Monitoring Committee concluded from preliminary interim data that the combination in these patients not only did not reduce the risk of such events, but actually increased it.

The company warned doctors worldwide not to prescribe aliskiren-containing products to patients with diabetes who were receiving an ACE inhibitor or ARB. This warning remains in place outside the EU pending further discussions.

Rasilez (Tekturna in the US) was approved in the EU and the US in 2007 for treatment of hypertension as a monotherapy or in combination with other drugs. It is available in tablet form in all EU Member States except Estonia, Latvia, Lithuania and Romania.

Novartis’ Galvus (vildagliptin) has been approved for use by the European Commission for patients with type 2 diabetes who cannot take metformin, the current standard treatment.

The approval is based on data from clinical trials which assessed the drug as a monotherapy and found the treatment delivered improvements in glycaemic control, was generally well-tolerated and associated with a low risk of hypoglycaemia.

David Epstein, Head of Novartis, expects the brand to develop into a “blockbuster, we believe, quite soon”.

Galvus is already approved in the EU as an add-on treatment to metformin, sulphonylureas and thiazolidinediones. Towards the end of 2011, it received approval for patients with type 2 diabetes and moderate or severe renal impairment.

Last year it recorded sales of $677 million, an impressive increase of 66%, despite not being available in the USA. But it is the latest approval which has caused excitement at Novartis. The company estimates that more than 47 million Europeans have type 2 diabetes. It estimates this total will rise to 57 million people by 2030, with a quarter of these people unable to take metformin due to intolerance or contraindications.

Novartis will axe nearly 2,000 positions in the US after restructuring its General Medicines business in new plans it says will strengthen its long-term position within the industry.

Its field force will be reduced by approximately 1,630 positions with a further 330 jobs removed from administrative functions after the loss of patent exclusivity on Diovan and the termination of the ALTITUDE study.

David Epstein, Division Head of Novartis Pharmaceuticals, says the job cuts are “difficult but necessary decisions” which will allow the company to invest in future opportunities.

The restructuring will take place in the spring and is expected to cost the company $160 million, which Novartis hopes will reflect annual savings of around $450 million by 2013.

Diovan, the market-leading hypertension medication, is expected to lose its patent protection in the US in September 2012. Demand for Rasilez is also expected to fall after the ALTITUDE trial was halted following the recommendation from the Data Monitoring Committee (DMC).

The study was investing Rasilez in patients with type 2 diabetes and renal impairment. But, as a precaution, it was ceased in combination with an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) after data indentified higher adverse effects when Rasilez was added. Novartis expects the move will lead to a loss in sales of $900 million.

In addition, the company also expects to lose around $160 million after the termination of its PRT128 (elinogrel) and SMC021 (oral calcitonin) programmes.

“We recognise that the next two years will be challenging in the Pharmaceuticals Division and we are proactively making these changes to further focus our pipeline on the best opportunities and align our market position on our growth brands,” said David Epstein.

Novartis has decided to terminate its ALTITUDE study with Rasilez/Tekturna (aliskiren) involving patients with type II diabetes and renal impairment who are at high risk of cardiovascular and renal events.

The independent Data Monitoring Committee (DMC) recommended the termination following a seventh interim review of data which identified higher adverse effects when the treatment was added to an ACE or ARB drug.

David Epstein, Division Head of Novartis Pharmaceuticals, says that “patient safety is the highest priority for Novartis” and the company is “in dialogue” with health authorities to address the implications of the study’s outcome.

The study, a placebo-controlled Phase III trial, is the first to investigate Rasilez/Tekturna for more than a year in patients with type II diabetes and renal impairment. More than 8,600 patients from 36 countries were evaluated in the study into the potential benefits of the medication to reduce the risk of cardiovascular and renal events.

The DMC concluded that patients were unlikely to benefit from the treatment when added to standard anti-hypertensives. Those receiving Rasilez/Tekturna in addition to standard care in the trial were also at an increased risk after 18-24 months of non-fatal stroke, renal complications, hyperkalemia and hypotension in this high-risk study population.

Rasilez/Tekturna-based products include:

• Rasilez/Tekturna
• Rasilez HCT/Tekturna HCT, a single-pill combination of Rasilez/Tekturna and hydrochlorothiazide (HCT)
• Valturna, a single-pill combination of Rasilez/Tekturna and valsartan – available in the US only
• Rasilamlo/Tekamlo, a single-pill combination of Rasilez/Tekturna and amlodipine
• Rasitrio/Amturnide, a triple combination of Rasilez/Tekturna, amlodipine and hydrochlorothiazide (HCT).

The monotherapy treatment for hypertension was approved in 2007 in the EU and US under the brand-names Rasilez and Tekturna respectively. Novartis says the efficacy and safety of the medication has been investigated in more than 57,000 patients in clinical studies.

Novartis’ ACZ885 (canakinumab) has met both of its primary endpoints in Phase III studies for the treatment of active systemic juvenile idiopathic arthritis (SJIA) treatment, the company has said.

Data showed that ACZ885 allowed nearly half (45%) of children with SJIA to reduce their use of steroids within 28 weeks and that patients were nearly three times less likely to suffer a new flare.

David Epstein, Head of the Pharmaceuticals Division of Novartis, says the data demonstrates “the significant benefits that ACZ885 may provide”.

The results of the trial, along with data from a second pivotal study, are planned to form the basis for worldwide regulatory submissions next year.

A total of 177 patients between the ages of 1 and 19 years with active SJIA were enrolled in the study. The primary endpoints were to assess if ACZ885 allows tapering of steroids in at least 25% of SJIA patients and demonstrates that time to flare is extended with ACZ885 versus placebo.

Only 27% of ACZ885-treated patients experienced a new flare, compared to three-quarters of patients on placebo.

"These data are very welcome because nearly half of ACZ885-treated patients were able to reduce their steroid use during the study, potentially helping decrease the impact that these drugs can have on this young population," said Dr Nico Wulffraat, one of the study investigators and pediatric immunologist at Wilhelmina Children's Hospital, University Medical Center in Utrecht, The Netherlands.

SJIA is the most serious form of childhood arthritis affecting less than one child per 100,000. Traditional therapies used to treat the condition only partially mitigate symptoms but do not usually prevent long-term damage. Long-term steroid use can also contribute to slowed growth, delayed puberty and reduced bone density.

Under the brand name Ilaris, ACZ885 is already approved in more than 50 countries, including the EU, US, Switzerland and Japan for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS). It is also being studies for use in other diseases which cause inflammation.

The CHMP has adopted a positive opinion for Novartis’ Rasitrio, recommended as replacement therapy for patients with high blood pressure.

The single-pill treatment combines calcium channel blocker amlodipine with the diuretic hydrochlorothiazide (HCT) and Rasilez, the only approved direct renin inhibitor in the world.

Professor Roland E. Schmieder at the University Hospital of the University Erlangen-Nuremberg, Germany, commented that the drug will provide patients with a “comprehensive and convenient high blood pressure treatment in one pill”.

The CHMP positive opinion of Rasitrio is based on a Phase III clinical trial involving more than 1,181 patients with high blood pressure. Data showed that Rasitrio significantly reduced blood pressure compared to dual combinations of each of its individual components.

David Epstein, Division Head of Novartis Pharmaceuticals, said: “This positive CHMP opinion is an important step towards approval and making this new triple combination therapy available for patients whose blood pressure is not under control and who may require multiple medications.”

Approximately 1 billion people have high blood pressure worldwide, with many remaining uncontrolled despite treatment, with up to 85% of patients requiring multiple medications to help control their blood pressure.

High blood pressure can cause damage to the heart, brain and kidneys and is also linked with other conditions such as diabetes.

Patients with high blood pressure in Europe are set to benefit after a new convenient single-pill treatment was approved by the European Commission.

Rasilamlo, a combination of aliskiren and amlodipine, has been given the green light for patients with high blood pressure not controlled by either aliskiren or amlodipine alone.

Professor Gordon McInnes, Professor of Clinical Pharmacology, Institute of Cardiovascular and Medical Sciences, University of Glasgow, says that research has shown an “innovative new single-pill” is needed.

It is estimated that around a billion people globally have high blood pressure with only an average of 8% of patients in the EU thought to have their condition under control.

The Novartis pills combines the only approved direct renin inhibitor in the world Rasilez with the widely used calcium channel blocker amlodipine.

It has been evaluated in clinical studies involving more than 5,000 patients with mild-to-severe high blood pressure. Data showed that Rasilamlo provides greater blood pressure reductions than Rasilez and amlodipine alone.

The single-pill combination works to lower blood pressure in two ways. The Rasilez component targets the activity of the renin angiotensin aldosterone system (RAAS), an important regulator of blood pressure. The calcium channel blocker amlodipine also lowers blood pressure by relaxing the blood vessel walls through the inhibition of calcium.

“We are pleased to announce that following today's EC approval Rasilamlo will now be available to high blood pressure patients in the EU who are not controlled by either aliskiren or amlodipine alone,” said David Epstein, Division Head of Novartis Pharmaceuticals (pictured). “This approval reinforces the Novartis commitment to developing new treatment options for patients with uncontrolled high blood pressure.”

Novartis has received the thumbs up for Gilenya (fingolimod) and Lucentis (ranibizumab) in Europe.

The European Commission has granted approval for Gilenya as a disease modifying therapy for relapsing-remitting multiple sclerosis (RRMS).

The CHMP has also given a positive opinion on Lucentis to treat visually impaired patients due to macular oedema secondary to retinal vein occlusion (RVO).

David Epstein, Head of Novartis Pharmaceuticals (pictured), said the company was “dedicated to bringing innovative new treatments to patients where there is significant unmet need” and was pleased with both decisions.

The convenient Gilenya capsule 0.5 mg daily has been granted approval for patients with RRMS patients despite treatment with beta interferon, or in patients with rapidly evolving severe RRMS.

Its approval was based on the largest clinical trial program submitted to date for a new MS drug. Data from the studies showed significant efficacy in reducing relapse, the risk of disability progression, and the number of brain lesions detected by magnetic resonance imaging (MRI).

Professor Hans-Peter Hartung, Professor and Chairman, Dept. of Neurology, Heinrich-Heine University, Germany, says Gilenya’s approval is “an important step forward” for patients.

Lucentis’ positive opinion was also based on data from two Phase III studies in patients with Branch RVO (BRAVO) and Central RVO (CRUISE). Studies showed that nearly 60% of BRVO and almost half (48%) of CRVO patients treated with monthly Lucentis gained at least 15 letters of visual acuity at six months, compared with 29% and 17% of those treated according to current standard practice, respectively.

“If approved, Lucentis would be the first anti-VEGF therapy licensed for the treatment of RVO in Europe,” said David Epstein.

“This would be in addition to the Lucentis approvals for patients with wet age related macular degeneration and patients with vision loss due to diabetic macular edema.”

Lucentis is currently licensed in more than 85 countries for the treatment of wet age-related macular degeneration (AMD) and in the European Union for visual impairment due to diabetic macular edema.