New analysis shows inclisiran consistency in LDL-C reduction as Novartis readies for FDA decision

As the FDA continues its review of the former-The Medicines Company, now-Novartis candidate inclisiran ahead of an expected PDUFA before the year is out, the Swiss pharma released pooled data that it hopes bolsters the case for approval.

A post-hoc analysis of two Phase III inclisiran trials showed consistency in efficacy and safety among patients with both hyperlipidemia and atherosclerotic cardiovascular disease despite statin therapy, with 99% of patients showing greater than 30% placebo-adjusted reduction in LDL-C levels. The average reduction was 54.1% from baseline in the 2,300 individuals between the two studies.

The analysis measured the candidate’s profile after 17 months of the first dose. Around 88% of patients hit 50% reduction of LDL-C in at least one point during the study, and after the 17-month period, almost two-thirds of patients (66.4%) had a 50% reduction compared to 2.5% percent in the placebo group.

Data for the study were taken from the ORION-10 trial, looking at hyperlipidemia, and the ORION-11 trial, examining ASCVD. Inclisiran hit primary endpoints of 52% and 50% LDL-C reduction, respectively, at 17 months.

Inclisiran works differently than the big-name LDL-C drugs on the market, such as Amgen’s Repatha and Sanofi/Regeneron’s Praluent. While those are monoclonal antibodies that inhibit the PCSK9 protein, inclisiran is a small interfering RNA that works to prevent PCSK9 from being synthesized in the liver.

Though those drugs have set the market pace since their approvals in 2015 with their efficacy levels, they disappointed out of the gate thanks to sticker shock at the initial prices of around $14,000. The drugmakers have since cut prices by about 60% though, making it tough for inclisiran to elbow its way into the competitive field.

Novartis is banking on added convenience, however, as a way to market inclisiran should it receive FDA approval as doctors only need to administer the compound twice a year, following an initial dose and a second dose three months later. Repatha and Praluent require dosing either every two weeks or once a month.

Inclisiran was largely seen as the big prize for Novartis when it acquired The Medicines Company for $9.7 billion last November. Though Novartis admitted in documents that the biotech likely wasn’t worth the $90 per share it was offering, the pharma decided to honor the initial price hoping to cash in on the drug.

The FDA is expected to reach a decision on inclisiran before the end of 2020 in the treatment for hyperlipidemia among adults who are on a maximally tolerated dose of statin therapy. It is also under review by the EMA.