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.

The European Commission (EC) has approved Novartis’ triple combination drug Rasitrio as a treatment for high blood pressure.

Rasitrio, the first combination of aliskiren, amlodipine and hydrochlorothiazide (HCT) in a single pill, has been shown to reduce blood pressure more effectively than dual combinations of any of its components.

The combination drug is based on Novartis’ direct renin inhibitor Rasilez (aliskiren), a successful regulator of high blood pressure.

The growing need for multiple medications to treat high blood pressure (estimated to be up to 85% of patients) is driving the market for combination drugs, which improve patient compliance.

Rasitrio lowers blood pressure in three ways:

• Aliskiren binds to and inhibits renin, an enzyme produced by the kidneys that can make blood vessels narrower.

• Amlopidine, a calcium channel blocker, relaxes the blood vessel walls.

• HCT, a diuretic, increases excretion of water and salt.

All three components also improve blood flow.

Hypertension affects as many as one billion people worldwide. Effective control can reduce the incidence of stroke and heart failure by half and heart attacks by one quarter.

The EC approval of Rasitrio is based on phase III data involving 1,181 patients, showing that the combination drug reduced blood pressure more effectively than dual combinations of any of its three components.

“Simplification of treatment for high blood pressure patients on three or more therapies is key to improving patient compliance and outcomes,” said Prof. Josep Redon, Hospital Clinico, University of Valencia, Spain.

“This innovative triple combination therapy, which has demonstrated significant reductions in blood pressure during clinical trials, offers patients a new and convenient treatment option.”

Novartis will cut 2,000 manufacturing jobs in Switzerland and the US – despite seeing an increase in group net sales and operating income in Q3.

The positions will be cut by 2016 after the closure of two Swiss production sites and one in Italy, plus the restructuring and relocation of R&D activities from Switzerland to the US.

Joseph Jimenez, CEO of Novartis, said the job losses are needed for the Group to “continue delivering on our mission of bringing innovative new drugs to patients.”

However, the job losses will be offset by the creation of 700 new positions in low cost and other countries, the company said.

The Group recorded a sales increase of 12% in constant currencies to $14.8 billion and saw income also grow by 11% to $4.1bn.

Sales were boosted by a strong performance from recently launched products – which contributed 25% of net sales.

Pharmaceutical sales grew 9% after Afinitor (pictured)/Votubia was approved in the EU for two additional indications, the CHMP granted a positive opinion for Rasitrio for high blood pressure and the company’s breakthrough multiple sclerosis treatment, Gilenya, won approval in Japan.

“Once again, the breadth of our business and product portfolio allowed us to deliver strong financial results and operating leverage, as well as significantly advancing the pipeline in the quarter,” said Mr Jimenez. “To strengthen our future, we have accelerated actions to reduce our cost base over the next few years.”

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.