The Medicines Company and RNA biotech partner Alnylam have set out a new, large late-stage test for their next-gen anticholesterol candidate inclisiran, which it hopes will get over the line for approval.
After its end-of-phase-2 meeting with the FDA, the pair are plotting a 3,000-patient-strong test focusing in on atherosclerotic cardiovascular disease and familial hypercholesterolemia (an inherited condition that causes high levels of LDL).
The primary endpoint for these pivotal trials will be LDL-C change from baseline, with patients split 50-50 on the injected inclisiran and a placebo for 18 months.
Although not required by the FDA, the drug partners said Med Co would also undertake a large cardiovascular outcomes trial in as many as 14,000 patients with ASCVD and/or risk equivalents, such as diabetes.
The design of this trial has already been approved by the FDA, with the primary efficacy endpoint being a composite of coronary heart disease death, nonfatal myocardial infarction (heart attack) and fatal and nonfatal ischemic stroke.
The test could be a long one, and long enough to build up data on the number of events to provide “overwhelming statistical power to ascertain treatment group differences and maximize the clinical effect size associated with LDL-C lowering,” Med Co says.
The FDA will see this as a supplemental NDA in the years to come, should it prove successful.
The drug is an investigational GalNAc-conjugated RNAi therapeutic targeting PCSK9. These inhibitors are already on the market, with Amgen’s Repatha (evolocumab) FDA-approved for heterozygous familial hypercholesterolemia; homozygous familial hypercholesterolemia, and clinical atherosclerotic cardiovascular disease, such as heart attacks or strokes.
Another PCSK9 from Sanofi and partner Regeneron, Praluent (alirocumab), has a similar license from the FDA, but is battling a patent dispute with Amgen that wants to stop its sales.
At the start of the year, a U.S. federal judge handed down a stunning loss for Sanofi and Regeneron with a ban on Praluent in the U.S. after a jury said it infringed on Repatha’s patents.
Med Co and Alnylam hope to have an edge over its rivals, despite being later to market, as its med should be longer-acting, although pricing will likely be the largest factor for the med, and the class, should it gain approval.