Novartis' first-in-class drug data 'encouraging'
treatment for hypertension. Aliskiren - the first in a new class of
antihypertensive drugs has shown to be effective as a single
treatment for patients with high blood pressure.
Despite the availability of many effective, well-tolerated drugs, a significant portion of treated hypertensive patients remain uncontrolled and face serious morbidity and mortality as a consequence.
The current challenges in drug treatment of hypertension include adherence to therapy and the need for most patients to take more than one drug to control their hypertension.
According to the World Health Organisation (WHO), hypertension affects approximately 50 million people in the USA and about 1 billion people worldwide. The WHO estimates that there are 7.1 million deaths each year (13 per cent of all mortality) due to complications of hypertension.
Data that emerged from early studies of aliskiren, indicated that the drug was effective as a single treatment for patients with mild-to-moderate uncomplicated essential high blood pressure.
Results of initial randomised controlled clinical trials also suggest that the new medication is well tolerated and that patients exhibit good adherence to the once-a-day oral medication.
Novartis already wields one of the world's top-selling blood pressure drugs, Diovan, which has annual sales of approximately $2 billion (€1.6 billion). News of this drug's progress will consolidate its advantage in the $40 billion hypertension drug market.
Numerous drug firms have pursued renin inhibitors on and off for decades, but it has been difficult to come up with effective treatments that can be given as once-a-day-pills, a crucial convenience factor in the crowded hypertension market.
Aliskiren is the first in a new drug class called renin inhibitors. Renin is an enzyme, which controls the formation of a substance called angiotensin II, the key mediator in the regulation of body fluid volume and blood pressure.
Aliskiren, which has not yet been approved by the US Food and Drug Administration, is currently in phase III trials as a stand-alone therapy and in phase II as combination therapy in patients with mild-to-moderate hypertension, and in phase II trials in patients with diabetic nephropathy.
Phase II data concluded that there was good evidence that as a stand-alone therapy aliskiren reduced blood pressure significantly compared with a placebo and was as effective as two commonly prescribed ARBs with a similar tolerability profile.
"For patients whose blood pressure can be controlled with single-agent therapy, aliskiren may offer another well-tolerated, effective alternative," the review concluded.
The article, which is reviewed in the latest issue of Core Evidence, also noted that, preliminary evidence from one study that adherence to aliskiren therapy is high, averaging more than 95 per cent.
The article observed that: "A good tolerability profile together with once-daily administration may be expected to positively influence adherence and quality of life, both of which can be significant barriers to effective disease management in patients with hypertension."
However, the review also noted that: "most patients with hypertension eventually need a second antihypertensive drug" and although "there is some evidence that aliskiren combined with an ARB is effective in reducing blood pressure," the use of aliskiren in combination therapy cannot be recommended without further study.
Current drug therapies for hypertension include diuretics, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, aldosterone receptor blockers (ARBs), calcium channel blockers, and alpha-1 blockers, used individually and in various combinations.
Existing drugs, including Diovan, Avapro from Bristol-Myers Squibb and Cozaar from Merck, as well as ACE inhibitors such as Vasotec, target later stages of the "renin-angiotensin" cascade - the body's core mechanism in blood pressure regulation.
These drugs remain problematic, as they struggle to control some patients' blood pressure over the long term. Indeed, these patients ultimately switch to multiple drug combinations to control the disease. Government estimates suggest only 25 per cent of hypertension cases are fully controlled with existing drugs.
One reason why hypertension is sometimes resistant to existing drugs, researchers theorise, may be that the body tries to counteract the effects of the other drugs by boosting levels of the errant enzyme renin.
It is theoretically possible for Novartis' researchers to combine aliskiren with Diovan to clamp down on this "escape mechanism" and provide the required blood pressure control.
