News | Pharmaceuticals | September 12, 2017

ORION 1 Trial Shows Inclisiran Lowers Bad Cholesterol Up to One Year

September 12, 2017 — Inclisiran lowers low-density lipoprotein (LDL, or “bad”) cholesterol for up to one year in patients with high cardiovascular risk and elevated LDL cholesterol, according to late-breaking results from the ORION 1 trial presented at the 2017 European Society of Cardiology (ESC) Congress.

“The ease of dosing – small volume subcutaneous injections twice a year most likely given by healthcare professionals – promises to improve patient adherence to lipid therapy, which has been a real problem with all other approaches,” said principal investigator Prof. Kausik K. Ray, professor of public health, Imperial College London, U.K., and honorary consultant cardiologist, Imperial College NHS Trust.

ORION 1 is a multicentre, placebo-controlled, double-blind, randomised phase II study on the impact of single or multiple subcutaneous injections of inclisiran on LDL cholesterol reductions over one year. Inclisiran is a first-in-class investigational drug that acts by turning off PCSK9 synthesis in the liver. The objective was to identify the dose and dosing frequency required for the phase III trials.

The trial included 501 patients with atherosclerotic cardiovascular disease (ASCVD) and elevated LDL cholesterol (>70 mg/ml) despite maximum tolerated statin therapy and patients without ASCVD but with high cardiovascular risk conditions such as diabetes and familial hypercholesterolaemia in whom LDL cholesterol was >100 mg/dl despite maximally tolerated statin therapy.

Patients were randomised into eight treatment groups: a single dose regimen of 200, 300 or 500 mg inclisiran, or placebo; or a two dose regimen of 100, 200 or 300 mg inclisiran, or placebo, at days one and 90.

The primary endpoint was the percentage change in LDL cholesterol at six months for each dose of inclisiran versus placebo. As previously reported, the two dose 300 mg inclisiran regimen gave the greatest reduction in LDL cholesterol at six months. (2)

Today researchers report results of one of the secondary endpoints, which was the change in LDL cholesterol at one year with one or two doses of inclisiran. Against a background therapy of statins (73%), alone or with ezetimibe (31%), the time averaged reductions in LDL cholesterol at one year with a single dose of 200, 300 or 500 mg inclisiran were -31.6, -38.1 and -39.8 percent, respectively. The time averaged reductions in LDL cholesterol at one year with a two dose regimen of 100, 200 or 300 mg inclisiran were -31, -41.1 and -46.8 percent, respectively.

As expected based on predictive modelling, patients began to return to their baseline LDL cholesterol values by an average of 2–3% per month, meaning they will be back to their starting levels by about 18–21 months for the two dose groups. Every patient on the two dose regimen had a significant response and the mean LDL cholesterol reductions over time were practically constant. Safety was generally similar between inclisiran and placebo apart from a small numerical excess of injection site reactions with the study drug.

“These one year data affirm and extend the six month results,” Ray explained. “The two dose 300 mg regimen produced the greatest reductions in LDL cholesterol, with an average time-adjusted fall of almost 50 percent at one year. The sustained LDL cholesterol lowering effects of inclisiran were achieved without side effects and were accompanied by predictable and gradual reversal. The data support dosing twice a year after initial injections on days one and 90.”

The study was sponsored by The Medicines Company.

Disclosures: Prof Ray reports acting as Consultant to The Medicines Company.

For more information: http://congress365.escardio.org

 

Links to all the late-breaking ESC 2017 trial presentations.

Reference: 

1, Ray KK, et al. Inclisiran in patients at high cardiovascular risk with elevated LDL cholesterol. N Engl J Med. 2017;376(15):1430–1440. doi: 10.1056/NEJMoa1615758. Epub 2017 Mar 17.
https://www.ncbi.nlm.nih.gov/pubmed/28306389

Related Content

BioCardia Announces 12-Month Results from TRIDENT Trial of Stem Cell Delivery System
News | Stem Cell Therapies| September 26, 2017
BioCardia Inc. recently announced 12-month results from the Phase II TRIDENT clinical trial, conducted by the...
News | Vena Cava Filters| September 26, 2017
September 26, 2017 — The one-year results of the SENTRY...
Treatment of Heart Attack Patients Depends on Cancer History
News | Cardio-oncology| September 26, 2017
Treatment of heart attack patients depends on their history of cancer, according to research published recently in...
CardiAMP Heart Failure Trial Design Presented at Texas Heart Institute Symposium
News | Heart Failure| September 25, 2017
BioCardia Inc. announced the trial design for its pivotal Phase III CardiAMP Heart Failure Trial was presented during...
Biotronik Studies Demonstrate Efficacy of Minimizing Metal Burden in SFA Therapy
News | Stents Bare Metal| September 22, 2017
Physicians demonstrated that reducing metal burden in superficial femoral artery (SFA) therapy could effectively reduce...
Edwards Inspiris Resilia Valve Receives FDA Approval
News | Heart Valve Technology| September 21, 2017
Edwards Lifesciences Corp. recently received U.S. Food and Drug Administration (FDA) approval for its Inspiris Resilia...
MyoKardia Presents Additional Positive Data From Phase 2 PIONEER-HCM Study at HFSA 2017
News | Heart Failure| September 21, 2017
MyoKardia Inc. announced that additional positive data from the first patient cohort of its Phase 2 PIONEER-HCM study...
DISRUPT BTK Study Shows Positive Results With Lithoplasty in Calcified Lesions Below the Knee
News | Peripheral Artery Disease (PAD)| September 20, 2017
Shockwave Medical reported positive results from the DISRUPT BTK Study, which were presented at the annual...
Heart Failure Market to Surpass $16 Billion by 2026
News | Heart Failure| September 19, 2017
The heart failure space across the seven key markets of the U.S., France, Germany, Italy, Spain, the U.K. and Japan is...
Corindus Announces First Patient Enrolled in PRECISION GRX Registry
News | Robotic Systems| September 18, 2017
September 18, 2017 — Corindus Vascular Robotics Inc.
Overlay Init