Analysis shows The Medicines Company/Alnylam drug inclisiran safe for renally-impaired patients
About a week after long-term Phase II data on The Medicines Company’s $MDCO Alnylam $ALNY-partnered twice-yearly cholesterol fighter, inclisiran, was indicated as safe and effective as the approved once-monthly Repatha and Praluent, its manufacturers presented data at the European Atherosclerosis Society Congress from two trials involving renally-impaired patients.
Altogether data from 279 patients across the two trials showed that patients with different levels of renal function achieved consistent reductions in low-density lipoprotein cholesterol (LDL-C), or “bad” cholesterol with inclisiran treatment, and did not require dose adjustment, The Medicines Co said over the weekend.
Renal impairment has been shown to frequently accompany and increase the risk of atherosclerotic cardiovascular disease (ASCVD) — but data from the Phase II ORION-1 trial and Phase I ORION-7 trial did not raise any safety concerns associated with inclisiran, analysts said.
Unlike Repatha from Amgen $AMGN, as well as Praluent from Regeneron $REGN and Sanofi $SNY — which work by inhibiting the PCSK9 protein and thereby diminishing LDL-C or “bad” cholesterol — inclisiran is a siRNA therapy designed to curb the production of the PCSK9 protein at its source in the liver to oust LDL-C from the bloodstream.
Despite the wide adoption of statins, such as Pfizer’s $PFE nearly $13 billion-at-peak Lipitor, hypercholesterolemia and associated cardiovascular disease is endemic in the United States, representing fertile ground for fresh, potent therapies to reap lucrative returns. Repatha and Praluent were first approved in 2015 in post-statin patients amidst much fanfare but instead faced insurer pushback for their high sticker prices ($14,000) that led to lower-than-expected adoption. However, since then, trials have demonstrated the PCSK9 inhibitors also significantly cut cardiovascular risk — data that are now reflected on their labels — as well as safe use in renally-impaired patients, and their manufacturers have also their prices by 60%, in a bid to boost tepid sales. So there is “nowhere for inclisiran to hide on either efficacy or safety (especially safety),” Baird analysts wrote in a March initiation note.
While renal impairment did affect inclisiran’s pharmacokinetic (PK) profile, with longer drug exposure and slower drug clearance in severely renally-impaired subjects, changes in inclisiran PK had effectively no impact on the drug’s pharmacodynamic (PD) profile, Baird analysts underscored.
Pivotal late-stage data on inclisiran are expected in the third quarter, and the company expects to submit regulatory applications in the United States and Europe soon after.
“PCSK9 inhibitors Praluent and Repatha have shown to be effective in lowering LDL-C in patients with renal impairment. With the ORION-7 results inclisiran joins the ranks of other PCSK9 inhibitors in demonstrating efficacy and safety in this important subset of ASCVD patients. In addition, the positive ORION-7 results provide the rational for the inclusion of patients with severe renal impairment in the ongoing ORION Ph.3 trials,” SVB Leerink analysts wrote in a note.