The Medicines Company has announced positive top-line results from the interim analysis with 180-day follow-up for all 501 patients enrolled in the ongoing ORION-1 phase two study of inclisiran, its investigational, first-in-class PCSK9 synthesis inhibitor.
In the interim analysis, inclisiran continued to demonstrate significant and durable LDL-C reduction, reaffirming the potential for a highly-differentiated, low-volume dosing regimen of two or three injections per year. Inclisiran was well tolerated, with no material safety issues, including no investigational drug-related elevation of liver enzymes, neuropathy or change in renal function, observed. Injection site reactions with inclisiran were infrequent, mild or moderate, and transient.
The Medicines Company has also announced that it has initiated the ORION-2 study of inclisiran in patients with homozygous familial hypercholesterolemia. The study will examine the efficacy, safety and tolerability of inclisiran in patients with the condition.
The Medicines Company has also initiated ORION-3, a phase two, open-label extension study, with an active comparator (evolocumab), for patients completing the ongoing ORION-1 study. The ORION-3 study will evaluate the efficacy, safety and tolerability of long-term dosing of inclisiran and will also measure the effects of treatment, including a comparison of the effects of inclisiran and evolocumab, as well as switching from evolocumab to inclisiran, on certain clinical and patient-reported endpoints.
Patients completing ORION-1 will receive inclisiran or evolocumab, based on the treatment received in ORION-1. Those patients who received inclisiran will receive inclisiran throughout the ORION-3 study. Those patients who received placebo will receive evolocumab as comparator for one year, and then switch to inclisiran for the remainder of the ORION-3 study. The estimated study period for ORION-3 is four years, or until inclisiran receives regulatory approval, whichever occurs first. Subject to discussions with regulatory authorities, the ORION-3 study will be conducted in parallel with the Phase 3 development program for inclisiran.