Therapy Areas: Diabetes
The Medicines Co, Alnylam Pharmaceuticals Start Phase III Clinical Trials of Inclisiran
6 November 2017 - - US-based biopharmaceutical company The Medicines Company (NASDAQ: MDCO) and US-based RNAi therapeutics developer Alnylam Pharmaceuticals, Inc. (NASDAQ: ALNY) have initiated the Phase III clinical program for inclisiran, with the commencement of patient dosing on November 1, 2017 in the ORION-11 trial, the companies said.

ORION-11 is a Phase III study of inclisiran versus placebo in patients with atherosclerotic cardiovascular disease (ASCVD), or ASCVD-risk equivalents (e.g., type 2 diabetes and familial hypercholesterolemia), and elevated LDL-cholesterol (LDL-C) despite maximum tolerated doses of LDL-C lowering therapies.

This is a double-blind study in which 1,500 eligible patients will be randomized 1: 1 to receive either inclisiran or placebo.

The primary objective of the study is to evaluate the effect of inclisiran treatment on % change in LDL-C levels from baseline at Day-510 and time-adjusted % change in LDL-C levels from baseline between Day-90 and Day-540.

Building on the highly-successful ORION-1 Phase II trial, which defined the optimal dosing of inclisiran for the Phase III clinical programme, in ORION-11, the starting dose of inclisiran is 300 mg given subcutaneously on Day-1 and Day-90, followed by maintenance doses of 300 mg of inclisiran given subcutaneously on Day-270 and Day-450.

The treatment and observation duration of ORION-11 is 18 months. Approximately 100 clinical sites in seven European countries and South Africa are participating in the study, which is being performed in partnership with Pharmaceutical Product Development, LLC, a leading global contract research organization.

The ORION-11 trial is one of four Phase III pivotal trials for inclisiran, which also include the ORION-10 trial in approximately 1,500 ASCVD patients treated in North America; the ORION-9 trial in approximately 400 patients with heterozygous familial hypercholesterolemia treated in North America, Europe, Israel and South Africa; and the ORION-5 trial in approximately 60 patients with homozygous FH treated in Europe, the Middle East and North America.

The company continues to expect that all of these trials will commence before the end of 2017 and, subject to the progress and results of the Phase III clinical programme for inclisiran, that data from the four trials that comprise the program will support the submission of a New Drug Application in the United States and a Marketing Authorization Application in the European Union at or around the end of 2019.

Inclisiran (formerly known as PCSK9si or ALN-PCSsc) is an investigational GalNAc-conjugated RNAi therapeutic targeting PCSK9 a genetically-validated protein regulator of LDL receptor metabolism being developed for the treatment of hypercholesterolemia.

In contrast to anti-PCSK9 monoclonal antibodies that bind to PCSK9 in blood, inclisiran is a first-in-class investigational medicine that acts by turning off PCSK9 synthesis in the liver.

The Medicines Co and Alnylam Pharmaceuticals, Inc. are collaborating in the advancement of inclisiran pursuant to the terms of their 2013 agreement. Under the terms of that agreement, Alnylam completed certain pre-clinical studies and the Phase I clinical study, with The Medicines Co leading and funding the development of inclisiran from Phase II forward, as well as potential commercialization.

RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development.
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