GIAPREZA® for injection is a vasoconstrictor and FDA-approved to increase blood pressure in adults with septic or other distributive shock. GIAPREZA® is approved by the European Commission and the UK Medicines Agency for the treatment of refractory hypotension in adults with septic or other distributive shock who remain hypotensive despite adequate volume restitution and application of catecholamines and other available vasopressor therapies. GIAPREZA® mimics the body’s endogenous angiotensin II peptide, which is central to the renin-angiotensin-aldosterone system, which in turn regulates blood pressure.
Angiotensin II raises blood pressure by vasoconstriction; increased aldosterone release via direct action of angiotensin II on the vessel wall is mediated by binding to the G-protein-coupled angiotensin II receptor type 1 on vascular smooth muscle cells which stimulates Ca2+/calmodulin dependent phosphorylation of myosin and causes smooth muscle contraction.
The pivotal phase III trial of angiotensin II for the treatment of high-output shock (ATHOS-3) was a randomized, placebo-controlled, double-blind, international, multicenter Phase III safety and efficacy trial in which 321 adults with septic shock or other distributive shock who had hypotension despite fluid and vasopressor therapy were randomized 1:1 to GIAPREZA® or placebo. The primary efficacy endpoint, an increase in blood pressure, was achieved by 70% of patients randomized to GIAPREZA® compared with 23% of patients treated with placebo; p < 0.0001 (a treatment effect of 47%).
Prescribing information for GIAPREZA® is available at www.giapreza.com. The European Summary of Product Characteristics is available on the EMA website: www.ema.europa.eu/en/medicines/human/EPAR/giapreza.
In Europe, PAION currently estimates a peak sales potential of approximately EUR 75 million to approximately EUR 90 million per year based on its own projections.