Alnylam, Medicines Company Announce Plans for Phase 3 Inclisiran Studies

The Medicines Company and Alnylam Pharmaceuticals on Wedsenday outlined the next step in the development process for investigational RNAi therapy inclisiran.

Both companies announced an agreement was made with The Food and Drug Administration on a Phase 3 program evaluating the drug’s efficacy in treating atherosclerotic cardiovascular disease (ASCVD) and familial hypercholesterolemia (FH).

The first study will enroll an approcimate 3,000 patients where investigators will randomly assign treatment so 1,500 patients will either recieve a 300 miligram dose of inclisiran four times over an 18 month period while the other half will receive the placebo, according to Xconomy. The main goal of this study is to assess the drug’s ability to reduce levels of low-density lipoprotein cholesterol (LDL-C), otherwise known as “bad” cholesterol.

Also, the partners will implement a seperate cardiovascular outcomes trial enrolling an approximate 14,000 patients diagnosed with ASCVD and/or risk equivalents like diabetes with the goal of analyzing the drug’s ability to lower the risk of heart attacks or strokes. Trials of this nature tend to take a few years, but investigators will determine if inclisiran acheived its primary efficacy endpoint based on a mix of coronary heart disease death, non-fatal myocardial infarction and fatal and non-fatal ischemic stroke.

“We are grateful to the FDA for its expertise, advice and support. Cardiovascular disease is a serious threat to the health of Americans, and it is clear that the FDA is committed to facilitating the development and approval of effective and safe drugs to address this important public health problem,” said the CEO of The Medicines Company Clive Meanwell, M.D., Ph.D., in a statement “Based on data from our Phase II ORION-1 study and the previous Phase I study – both published in The New England Journal of Medicine – we are confident that inclisiran reduces LDL-C meaningfully. We have also been highly encouraged by the safety data in these prior studies. Furthermore, inclisiran’s highly-differentiated dosing schedule has the potential to transform the burden placed on millions of patients who so badly need to lower LDL-C levels.

The hope is that inclisiran’s mechanism of action turning off the synthesis of PCSK9, the protein regulator of LDL receptor metabolism, in the liver instead of the blood combined with a more convenient dosing schedule could make it a viable alternative compared to products like Amgen’s Repatha.

Alnylam and Medicines Co. hope to file for regulatory approval sometime in 2019, but data from the outcomes trial could be part of a seperate supplemental NDA.