La Jolla Pharmaceutical Company, a leader in the development of innovative therapies intended to significantly improve outcomes in patients suffering from life-threatening diseases, has initiated its ATHOS (Angiotensin II for the Treatment of High-Output Shock) 3 trial, a phase 3 clinical trial of LJPC-501 for the treatment of catecholamine-resistant hypotension (CRH).
In February 2015, La Jolla reached agreement with the US Food and Drug Administration (FDA) on a Special Protocol Assessment (SPA), in which it was agreed that the primary efficacy endpoint for the trial would be increase in blood pressure. CRH is an acute, life-threatening condition in which blood pressure drops to dangerously low levels in patients who respond poorly to current treatments.
In accordance with the SPA, the ATHOS 3 trial is a multicenter, randomized, double-blind, placebo-controlled, phase 3 clinical trial of LJPC-501 in patients with CRH. The ATHOS 3 trial is designed to enroll approximately 315 patients. Patients will be randomized 1:1 to receive either LJPC-501 plus standard-of-care vasopressors or placebo plus standard-of-care vasopressors. Randomized patients will receive their assigned treatment via continuous IV infusion for up to 7 days.
The primary efficacy endpoint of the ATHOS 3 trial is to compare the change in mean arterial pressure between the two groups in the trial. Secondary endpoints include comparison of changes in Sequential Organ Failure Assessment scores and the safety and tolerability of LJPC-501 in patients with CRH. La Jolla has reached agreement with the FDA that an adequately sized phase 3 trial comprised of 200-300 patients would provide a sufficient safety database to support FDA review and consideration for marketing approval.
“The prognosis for patients suffering from CRH is very poor, and current treatment options are limited. We believe that LJPC-501 has the potential to reverse hypotension and, therefore, provide a significant benefit to these difficult-to-treat patients,” said Lakhmir Chawla, M.D., Associate Professor of Medicine, Department of Anesthesiology and Critical Care Medicine, George Washington University.
“We are pleased to have advanced LJPC-501 into a phase 3 registration clinical trial,” said George F. Tidmarsh, M.D., Ph.D., president and chief executive officer of La Jolla. “We would like to thank the FDA and our clinical collaborators for helping us to advance this medically important program so expeditiously.”
LJPC-501 is La Jolla’s proprietary formulation of angiotensin II. Angiotensin II, the major bioactive component of the renin-angiotensin system, serves as one of the body’s central regulators of blood pressure. La Jolla is developing LJPC-501 for the treatment of catecholamine-resistant hypotension (CRH), which is an acute, life-threatening condition in which blood pressure drops to dangerously low levels in patients who respond poorly to current treatments. Angiotensin II has been shown to raise blood pressure in a randomized, placebo-controlled clinical trial in CRH, as well as animal models of hypotension. In October 2014, La Jolla presented positive data from a preclinical study of LJPC-501 for the treatment of CRH. La Jolla is currently enrolling patients into its ATHOS (Angiotensin II for the Treatment of High-Output Shock) 3 trial, which is a multicenter, randomized, double-blind, placebo-controlled, phase 3 clinical trial of LJPC-501 in patients with CRH.
La Jolla is also developing LJPC-501 for hepatorenal syndrome (HRS). HRS is a life-threatening form of progressive renal failure in patients with liver cirrhosis or fulminant liver failure. In these patients, the diseased liver secretes vasodilator substances (e.g., nitric oxide and prostaglandins) into the bloodstream that cause under-filling of blood vessels. This low blood pressure state causes a reduction in blood flow to the kidneys. As a means to restore systemic blood pressure, the kidneys induce both sodium and water retention, which contribute to ascites, a major complication associated with HRS. Studies have shown that LJPC-501 may improve renal function in patients with conditions similar to HRS. La Jolla is currently enrolling patients into a phase 1/2 clinical trial of LJPC-501 in HRS.