'Robust' Drop in LDL-C From Novel PCSK9 Synthesis Inhibitor: Early Results

Patrice Wendling

October 19, 2016

PARSIPPANY, NJ — The Medicine's Company announced that its first-in-class proprotein convertase subtilisin/kexin type 9 synthesis inhibitor PCSK9si continues to show "robust and durable" knockdown of LDL cholesterol up to 90 days in an interim analysis of the ORION-1 study.

Unblinded safety data revealed no drug-related elevation in liver enzymes, neuropathy, or change in renal function and "infrequent, mild or moderate, and short-lived" injection-site reactions, according to the company press release[1].

The investigational drug, also known as ALN-PCSsc, is being developed for the treatment of hypercholesterolemia and, unlike anti-PCSK9 monoclonal antibodies that bind to PCSK9 in blood, acts by inhibiting PCSK9 synthesis in the liver.

In a prior single-ascending dose study PCSK9si was associated with a maximal LDL-C reduction of 78.1%, the company noted.

The phase 2 ORION-1 trial of single or multiple subcutaneous injections of PCSK9si is testing several doses and the potential for dosing no more than two, three, or four times per year.

In the release, Dr John JP Kastelein (Academic Medical Center of the University of Amsterdam, Sweden) commented, "The potential for management of hypercholesterolemia with two or three low-volume injections per year could open a new, transformative, and affordable pathway for patients and physicians in the treatment of atherosclerotic cardiovascular disease."

Data from day 90 follow-up for all 501 patients and preliminary day 180 follow-up for up to 200 patients is scheduled for presentation in a late-breaking clinical-trial session November 15 at the American Heart Association 2016 Scientific Sessions in New Orleans and coverage by heartwire from Medscape.

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