Novartis Pharma has reported that its investigational product LCZ696, an angiotensin receptor neprilysin inhibitor (ARNI), has successfully completed its first large-scale clinical trial, highlighting the potential of the compound in the treatment of hypertension and other cardiovascular diseases.
LCZ696 is a novel-acting compound with distinctive chemical and biological properties; upon oral administration, it simultaneously inhibits both NEP and the angiotensin receptor. By targeting these two neurohormonal systems at the same time, LCZ696 may provide additional cardio-renal protection over current therapies for the treatment of cardiovascular disease.
The angiotensin (AT1) receptor is an established pharmacologic target for BP control and the treatment of symptomatic heart failure. NEP is an enzyme responsible for the breakdown of natriuretic peptides that can help to counteract many of the physiologic and structural changes associated with heart failure. Therapy that enhances the effects of natriuretic peptides through NEP inhibition is expected to be an attractive therapeutic approach to the treatment of this disease.
In a Phase II study, patients with mild-to-moderate hypertension were randomised to receive eight weeks of treatment with one of three doses of LCZ696, three comparable doses of the angiotensin receptor blocker (ARB) valsartan, the neprilysin (NEP) inhibitor pro-drug AHU377, or placebo.
Patients in the study receiving any one of the three active treatments achieved incremental blood pressure (BP) reductions on average over placebo. However, patients who received the two higher doses of the dual-acting LCZ696 achieved greater average reductions from baseline in both mean sitting systolic and diastolic BP than those in the comparator arms.
In addition, patients receiving high-dose LCZ696 also achieved superior BP control rates and significantly greater decreases in pulse pressure. LCZ696 was well tolerated, with no cases of angioedema reported.
Luis Ruilope, principal investigator of the study, said: “LCZ696, the first ARNI to be evaluated in a clinical trial, has demonstrated superior BP-lowering efficacy as compared to an ARB in patients with hypertension. These findings build promise for this novel drug class. In addition, these study results demonstrate the potential for managing cardiovascular diseases through enhancement of the beneficial effects of the body’s own natriuretic peptides via neprilysin inhibition and concomitant blockade of the angiotensin receptor.”
Ameet Nathwani, global head of development cardiovascular and metabolism franchise at Novartis Pharma, said: “Given its unique mechanism of action, we believe LCZ696 may have the profile to become the new standard of care for people living with heart failure, where there remains a significant and growing unmet need. In addition, Novartis is exploring the potential of LCZ696 for the treatment of high blood pressure among certain sub-populations who may derive particular benefits from its dual mode of action.”