With long-term data, Med Co, Alnylam’s cholesterol-fighter inclisiran poised for 2019 filing

Green light
The Medicines Company expects to file inclisiran for FDA approval by the end of 2019, with a European submission to follow in 2020. (StockSnap / Pixabay)

The Medicines Company announced long-term data for its Alnylam-partnered siRNA drug inclisiran, showing that the drug consistently lowered “bad” LDL cholesterol by more than 50%. The company expects to reveal pivotal phase 3 data in the third quarter and to file for FDA approval before the year is out. 

The data, announced during a late-breaking clinical trial session at the National Lipid Association scientific sessions, come from a group of 290 patients participating in an extension of a phase 2 study. The original trial, ORION-1, tested inclisiran in patients with atherosclerotic cardiovascular disease who had high LDL cholesterol levels despite taking the highest dose of cholesterol-lowering statins they could tolerate. Investigators followed those patients for one year. Of the ORION-1 patients, 382 enrolled in the extension, with 290 patients receiving a 300-mg injection of inclisiran twice a year and 92 patients receiving injections of Amgen’s Repatha (evolocumab) every two weeks for a year, before switching to inclisiran for three years. Investigators expect to present data for the second group in 2022. 

The interim analysis for the data showed that inclisiran lowered LDL cholesterol levels by 51% through day 210 of the study, meeting its primary endpoint. If approved, inclisiran would compete with Repatha and Regeneron and Sanofi’s Praluent, which are both antibodies against PCSK9, a protein that blocks the liver’s ability to clear LDL cholesterol from the blood. Unlike Repatha and Praluent, inclisiran lowers cholesterol not by targeting the PCSK9 protein, but by interfering with the production of PCSK9 itself. 

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“The strong data from ORION-3 bolster our confidence in inclisiran’s robust therapeutic profile which offers a vastly different value proposition compared to any other LDL-C lowering option,” said Mark Timney, CEO of The Medicines Company, in a statement. 

“These new data from ORION-3 provide further evidence of inclisiran’s unprecedented ability to deliver persistent LDL-C reductions over a prolonged period, which can help more patients reliably achieve LDL-C goals. Inclisiran also demonstrated a favorable safety profile, an important consideration given the long duration of LDL-C treatment,” said John J.P. Kastelein, M.D., Ph.D., ORION-3 study chair and a professor of medicine at the University of Amsterdam. 

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In addition to attacking PCSK9 at its source, the longer-acting inclisiran could address another challenge in treating heart disease: poor adherence. Both Repatha and Praluent are given as injections once or twice a month, and other medicines, such as statins, can be a daily burden on patients. 

“We believe this dosing schedule is attractive to patients and can improve adherence, since currently only 55-60% patients are compliant on PCSK9 Ab therapy,” wrote Jefferies analysts in a note. 

The Medicines Company plans to follow up its FDA submission with a European filing in the first quarter of 2020. 

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