Inclisiran is the first and only drug for cholesterol in the siRNA class.
The Medicines Company announced positive topline data from its ORION-10 Phase III clinical trial of inclisiran for atherosclerotic cardiovascular disease (ASCVD) as well as its ORION-9 Phase III study of the drug in Heterozygous Familial Hypercholesterolemia (HeFH). In ORION-10, the drug met all primary and secondary endpoints, showing efficacy, tolerability and safety that was at least as good as what was seen in ORION-11. There were no treatment-related liver or kidney abnormalities found in laboratory tests.
Inclisiran is the first and only drug for cholesterol in the siRNA class. It prevents production of the PCSK9 protein in the liver. This improves the liver’s removal of LDL-C, a type of cholesterol. Two other drugs on the market, Amgen’s Repatha (evolocumab) and Regeneron Pharmaceuticals and Sanofi’s Praluent (alirocumab) affect PCSK9, but differently than inclisiran. They bind to excess PCSK9, allowing it to be cleared from the body. Inclisiran basically prevents the liver from manufacturing PCSK9.
Both Praluent and Repatha have struggled to gain traction in the marketplace, largely because of price. Both drugs originally ran about $14,000 per year for a year’s supply. In February 2019, Sanofi and Regeneron cut the price of Praluent to about $5,850, while Amgen cut the price of Repatha in October 2018. Insurers have been reluctant to reimburse the drugs because of their high prices. Primarily the drugs have been for patients who don’t respond to diet, exercise and the far more affordable statin drugs. Statins, such as Pfizer’s Lipitor, are typically priced at about $50 per month.
One of the key factors that would make inclisiran an attractive treatment for high cholesterol, if it is approved, it that it would be injected only twice a year. Praluent and Repatha are injected once or twice a month.
The Medicines Company also indicated it will have a “flexible” pricing strategy. What that strategy will be hasn’t been revealed, although it does say the drug will be high-volume, lower-cost, so it could decrease the price fairly quickly as more patients are prescribed.
The company did not provide detailed data from the clinical trial, which will be presented at the American Heart Association Scientific Sessions in Philadelphia.
“The results seen in ORION-10 again demonstrate inclisiran’s outstanding efficacy, tolerability and safety,” said Mark Timney, The Medicines Company’s chief executive officer. “This is further validation of the potential of this first and only investigational cholesterol-lowering therapy in the siRNA class to transform the treatment of cardiovascular disease for millions of people with ASCVD.”
The ORION program is made up of ORION-9, ORION-10 and ORION-11. The company also released data from ORION-9 today, which is evaluating the drug in patients with Heterozygous Familial Hypercholesterolemia (HeFH). It too met all primary and secondary endpoints, with no treatment-related liver or renal abnormalities observed in lab tests. Detailed data will also be presented at the AHA Scientific Sessions.
FH is an inherited disease that results in high levels of LDL-C and causes early onset of heart disease. It affects about one in 250 people around the world, or about 1.3 million in the U.S. About 90% of people with it haven’t been diagnosed. HeFH is the most common type.
“The devastating cumulative effects of high LDL-C are more pronounced in people with FH, many of whom do not reach their treatment goals despite having significantly increased risk of cardiovascular disease,” Timney said. “The results of ORION-9 strongly support inclisiran’s potential in this patient population where the disease severity is highest.”
The company says it plans to file with the U.S. Food and Drug Administration (FDA) in the fourth quarter of this year and with the European Medicines Agency (EMA) in the first quarter of 2020.
