Positive results have been reported from a phase 3 trial of LJPC-501 (La Jolla Pharmaceutical Company) in patients with catecholamine-resistant hypotension (CRH). LJPC-501 is a proprietary formulation of synthetic human angiotensin II. Endogenous angiotensin II, the major bioactive component of the renin–angiotensin system, is one of the body’s central regulators of blood pressure. LJPC-501 is the first synthetic human angiotensin II product candidate to be tested in a phase 3 study.
The ATHOS-3 (Angiotensin II for the Treatment of High-Output Shock-3) trial was a randomized, double-blind, placebo-controlled study of LJPC-501 in 321 patients with CRH in nine countries. The patients were randomly assigned to receive either LJPC-501 or placebo on a background of standard-of-care vasopressors selected by the investigators. The patients received their assigned treatment via continuous intravenous infusion.
The study’s primary efficacy endpoint was the percentage of patients with mean arterial pressure (MAP) of 75 mm Hg or greater, or a 10-mm Hg increase from baseline MAP at three hours after the initiation of study treatment without an increase in standard-of-care vasopressors.
The primary efficacy result was statistically significant: 70% of 163 patients treated with LJPC-501 showed a blood pressure response compared with 23% of 158 placebo-treated patients (P < 0.00001). In addition, the patients receiving LJPC-501 demonstrated a nonsignificant 22% reduction in mortality risk through day 28 compared with the placebo-treated patients (hazard ratio, 0.78; P = 0.12].
Throughout the study, safety outcomes were followed by an independent data safety monitoring board, which recommended that the study continue as originally planned. In this critically ill patient population, 87% of patients treated with LJPC-501 experienced at least one adverse event compared with 92% of placebo-treated patients. Moreover, 14% of patients receiving LJPC-501 discontinued treatment because of an adverse event compared with 22% of placebo-treated patients.
CRH is a life-threatening syndrome in patients with distributive shock (dangerously low blood pressure with adequate cardiac function) who cannot achieve target mean arterial pressure (MAP) despite adequate fluid resuscitation and treatment with currently available vasopressors (catecholamines and/or vasopressin). Approximately 500,000 individuals experience distributive shock in the United States each year. Of these, an estimated 200,000 develop CRH. More than 50% of CRH patients die within 30 days.
Source: La Jolla Pharmaceutical Company; February 27, 2017.