A phase 3 trial of The Medicines Company’s cholesterol-lowering drug inclisiran has met its primary endpoint. The company is yet to share the efficacy data that will show whether inclisiran can compete with other PCSK9 drugs but has sought to tackle lingering safety concerns, noting the profile see in phase 3 was “at least as favorable” as in earlier trials.
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 (LDL-C). The drug is designed to stop the production of the PCSK9 protein, thereby achieving similar efficacy to Amgen’s Repatha and Sanofi and Regeneron’s Praluent with a far less onerous dosing schedule.
Today, Medicines Company revealed the first phase 3 trial of inclisiran hit its primary endpoints and all secondary efficacy objectives. The primary endpoints tracked changes in LDL-C out to 18 months after the start of treatment.
The top-line findings show inclisiran is more effective at lowering LDL-C than the statins, plus in some cases ezetimibe, the study participants tried without success prior to enrolling in the trial. But the lack of data on the changes in LDL-C makes it impossible to tell whether inclisiran is competitive. In a similar patient population, Repatha and Praluent lowered LDL-C by about 55%. An earlier phase 2 trial linked inclisiran to a 51% reduction after 210 days.
Medicines Company will share a detailed look at the pivotal trial data at the European Society of Cardiology’s (ESC's) annual congress at the start of next month. Until then, the only indicator of the level of efficacy seen in the trial is Medicines Company’s comment that the data are consistent with phase 1 and 2 results.
The company provided a similar qualitative assessment of the safety profile, claiming it is “at least as favorable” as that seen in earlier trial. A clean set of safety data would eliminate one of the doubts about the prospects of inclisiran.
Those doubts stem from inclisiran’s use of Alnylam’s Galnac delivery platform. Galnac also underpins Alnylam’s givosiran, which multiple trials have linked to liver toxicity. Recent trial readouts distanced inclisiran from those concerns, but there remained fears that testing the drug in a larger number of patients would reveal safety problems. While Medicines Company is yet to share data, its comments suggest those fears were unfounded.
Attention will now turn to the ESC presentation and readouts from two other clinical trials scheduled for later in the third quarter. If the data meet expectations, Medicines Company will file for FDA approval in the fourth quarter, with a European submission to follow early in 2020. However, even if inclisiran comes to market, the relative commercial failures of Repatha and Praluent mean it is unclear whether the drug will be a big seller for Medicines Company.