- The Medicines Company reported positive data Wednesday from a Phase 3 trial of the cholesterol-lowering drug inclisiran that confirms its benefit in patients with established heart disease, as well as from a second study in patients with genetically-driven high cholesterol.
- The New Jersey-based company will detail full data at the American Heart Association (AHA) meeting in November. Results of its first Phase 3 study of inclisiran were revealed at the European Society of Cardiology (ESC) meeting earlier this month.
- Executives expect to apply for Food and Drug Administration approval by the end of 2019. Inclisiran would compete with Amgen's Repatha and Sanofi and Regeneron's Praluent, with the potential commercial advantage of less frequent dosing.
Successful readouts of the Orion-9 and -10 trials completes the data package that the Medicines Company plans to submit to the FDA to support inclisiran's approval. Orion-11, which resembled -10 in almost every way, was presented to cardiologists at ESC, and will be part of that FDA submission.
Inclisiran lowers low-density lipoprotein (LDL), so-called bad cholesterol, using a pathway similar to Repatha (evolocumab) and Praluent (alirocumab).
The difference is that inclisiran blocks genetic expression of a protein called PCSK9, while Repatha and Praluent block it after it has already been produced in the body. Inclisiran is injected once every six months, while Repatha and Praluent must be dosed at least once a month.
Because the results of the two trials announced Wednesday are part of late-breaking presentations at AHA, Medicines Company did not release full data. However, it did report that data from both were positive.
Orion-9 shows that inclisiran can be effective in lowering LDL in patients with one copy of a gene that can lead to elevated LDL, a condition called heterozygous familial hypercholesterolemia. When added to statins, it significantly reduced LDL 510 days after the first treatment, the primary endpoint of the trial, along with all other measures investigators analyzed.
Orion-9 enrolled 482 patients randomized to take either placebo plus statins or inclisiran plus statins.
Orion-10 showed an LDL-lowering benefit of inclisiran plus statins in patients with established cardiovascular disease as defined by a narrowing of blood vessels thanks to fatty plaques. As with Orion-9, LDL was measured 510 days after first treatment as a primary endpoint, and the company announced it showed a statistically significant benefit on that measure along with all others analyzed.
The company said Orion-10 "demonstrated efficacy, tolerability and safety that were at least as favorable as observed in ORION-11," in which inclisiran lowered LDL by 54% when compared to placebo.
The two trials enrolled a similar number of patients with cardiovascular disease, 1,561 for Orion-10 compared with 1,617 for Orion-11. The big difference was that Orion-11 included patients without established disease but who did have risk factors for heart disease, which include diabetes or high blood pressure.
Shares in Medicines Company rose nearly 10% Wednesday morning, to a 19-month high of $51.
The findings may also benefit Alnylam Pharmaceuticals, from whom the Medicines Company licensed inclisiran. Cantor Fitzgerald analyst Alethia Young wrote in a Sept. 25 note to clients that the data confirm the safety of Alnylam's drug discovery platform, which prevents expression of proteins by blocking messenger RNA.