LCZ696

LCZ696 is an investigational combination drug consisting of two antihypertensives (blood pressure lowering drugs), valsartan and AHU-377, in a 1:1 mixture. It is being developed by Novartis. The combination is often described as a dual-acting angiotensin receptor-neprilysin inhibitor (ARNi) although the two effects are achieved by two different molecules.

In Phase II clinical trials, LCZ696 was superior to valsartan alone in treating hypertension, and well tolerated. , a Phase III study for the same indication is under way. Additionally, the drug combination is being tested for the treatment of chronic heart failure. It is not clear whether LCZ696 is superior to the combination of valsartan with hydrochlorothiazide which has been marketed since the 1990s.

Mechanism of action
Valsartan blocks the angiotensin II receptor type 1 (AT1) and thereby causes vasodilatation and increases excretion of sodium and water via the kidneys (by reducing aldosterone production). The latter mechanism leads to a reduction in blood volume.

AHU-377 is a prodrug that is activated to LBQ657 by de-ethylation via esterases. LBQ657 inhibits the enzyme neprilysin, which is responsible for the degradation of atrial and brain natriuretic peptide, two blood pressure lowering peptides that work mainly by reducing blood volume.