The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for Rasilamlo(TM) (aliskiren and amlodipine, Novartis) to treat high blood pressure patients not adequately controlled by either aliskiren or amlodipine alone. Rasilamlo combines in a single pill the only approved direct renin inhibitor worldwide, Rasilez?, with the widely used calcium channel blocker amlodipine.
The CHMP recommendation forms the basis for a European Commission licensing decision, which is expected in approximately three months. “We are delighted with the CHMP opinion because it means that Rasilamlo could soon be made available to patients in the EU in need of effective combination treatments to help control their high blood pressure,” said David Epstein, Division Head of Novartis Pharmaceuticals. “Novartis understands the complex needs of high blood pressure patients and is committed to furthering cardiovascular research and to developing innovative and effective treatments.”
Study results
The CHMP positive opinion of Rasilamlo is based on clinical trial data involving more than 5,000 patients with mild-to-moderate high blood pressure. An eight-week, randomized, double-blind, placebo-controlled, multi-factorial study showed that the combination of Rasilez and amlodipine resulted in decreases in systolic/diastolic blood pressure at trough of 14-17/9-11 mmHg, compared to 4-9/3-4 mmHg for Rasilez alone, and 9-14/6-8 mmHg for amlodipine alone[1].
In two additional double-blind, active-controlled studies of similar design evaluating patients with moderate-to-severe high blood pressure (systolic blood pressure [SBP] 160 – 200 mmHg), Rasilamlo demonstrated significantly greater reductions in systolic and diastolic blood pressures when compared to amlodipine alone[1]. In one study of 443 patients, the systolic/diastolic treatment difference between Rasilez and amlodipine was 5.2/3.8 mmHg at the primary endpoint of eight weeks[1]. In the other study of 484 patients, the treatment difference between Rasilez and amlodipine was 7.1/3.8 mmHg at endpoint[1].
How it works
The single-pill combination Rasilamlo 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. Rasilez directly binds to and inhibits renin, an enzyme produced by the kidneys that starts a process that can make blood vessels narrow and lead to high blood pressure[4]. The calcium channel blocker amlodipine lowers blood pressure by relaxing the blood vessel walls through the inhibition of calcium. Both of these medicines enable blood to flow more easily therefore lowering blood pressure.
Up to 85% of patients with high blood prerssure may need multiple medications to help control their high blood pressure underscoring the need for effective combination treatments[2, 3]
“Single-pill combination therapies can simplify the challenging treatment regimens of high blood pressure patients on multiple medications,” said Professor Gordon McInnes, Professor of Clinical Pharmacology, Institute of Cardiovascular & Medical Sciences, University of Glasgow. “Rasilamlo demonstrated greater blood pressure reductions than either aliskiren or amlodipine alone in clinical studies and can be expected to provide a convenient new treatment option to consider for uncontrolled patients.”
It is estimated that about one billion people globally have high blood pressure[5],[6], and many of these remain either untreated or treated but not at their blood pressure target[7]. High blood pressure can cause damage to the vital organs of the body, including the heart, brain and kidneys[6]. However, if high blood pressure is properly controlled, the incidence of stroke and heart failure can be reduced by almost half and heart attacks by one quarter[6].
References
[1] Rasilamlo (aliskiren and amlodipine) Tablets DRAFT Prescribing Information. February 2011.
[2] Dahlof B, et al. Cardiovascular Morbidity and Mortality in the Losartan Intervention for Endpoint Reduction in Hypertension Study (LIFE): a Randomised Trial Against Atenolol. Lancet 2002;359:995-1003.
[3] Pepine CJ, Handberg EM, Cooper-DeHoff RM, et al. A Calcium Antagonist vs. a Non-Calcium Antagonist Hypertension Treatment Strategy for Patients with Coronary Artery Disease. The International Verapamil-Trandolapril Study (INVEST): a Randomized Controlled Trial. JAMA 2003;290:2805-2816.
[4] Rasilez Summary of Product Characteristics (SmPC) for European Union.
[5] Kearney P, et al. Global Burden of Hypertension: Analysis of Worldwide Data. Lancet 2005;365:217-23.
[6] Chobanian AV, et al. Seventh Report of the Joint National Committee on Prevention, Detection Evaluation and Treatment of High Blood Pressure. Hypertension 2003;42:1206-1251.
