The Medicines Company has wrapped the last of three phase 3 studies for its PCSK9 drug inclisiran, reporting that it cut "bad" LDL cholesterol in patients with atherosclerosis, or plaque buildup in their arteries. The biotech hasn’t yet shared specifics but said the drug’s safety and efficacy were “at least as favorable” as seen in earlier trials.
The study hit its primary endpoints: the percentage change of LDL cholesterol from baseline after 17 months of treatment and the time-adjusted percentage change of LDL cholesterol from baseline after three months and 18 months. It also met its secondary endpoints: the mean absolute change in LDL cholesterol at 17 months, the average absolute reduction in cholesterol between three months and 18 months and changes in other lipids and lipoproteins, the company said.
It will present the full data at the American Heart Association scientific sessions in November.
“The results seen in ORION-10 again demonstrate inclisiran’s outstanding efficacy, tolerability and safety,” said Mark Timney, CEO of The Medicines Company. “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.”
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The Medicines Company licensed the rights to inclisiran from Alnylam Pharmaceuticals and embarked on a large pivotal trial program to assess its effect in patients with stubbornly high levels of LDL cholesterol despite taking the highest dose of cholesterol-busting statins they could. Two of its pivotal studies focused on patients with atherosclerosis, while the third, ORION-9, tested inclisiran in patients with heterozygous familial hypercholesterolemia (HeFH), an inherited disorder that causes dangerously high cholesterol levels. The company will also present full data from the HeFH study in November.
The company looks on track to file inclisiran for FDA approval by the end of the year. It plans to follow its FDA submission with a European filing in early 2020.
If approved, inclisiran would compete with Amgen's 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.
The longer-acting inclisiran could also be favored over its potential rivals as it is expected to boost adherence. Inclisiran was given at the beginning of the study, at the three-month mark and then every six months after that. 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 earlier this year.