The dyslipidemia market has two PCSK9 inhibitors: Sanofi and Regeneron’s Praluent (alirocumab) and Amgen’s Repatha (evolocumab). There is also a novel PCSK9 targeting therapy, Novartis’ small interfering ribonucleic acid, inclisiran, that has been submitted for FDA and European Medical Association (EMA) approval in adults with atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia who have elevated LDL-C while on statin therapy. Recently, a post-hoc analysis of inclisiran from Phase III trials, ORION-10 and ORION-11, was presented during the 2020 ESC conference. The positive data presented has led GlobalData to believe that Novartis has the opportunity to penetrate the market of patients unable to reach recommended LDL-C levels, by avoiding missteps taken with the PCSK9 inhibitors, while also putting forward a strong marketing campaign highlighting inclisiran’s strong data set and less frequent dosing schedule.

The post-hoc analysis presented at the ESC, which pooled data from more than 2,300 patients, showed that the twice-yearly subcutaneous gene-silencing treatment in patients already on statin therapy resulted in the decrease in LDL-C levels by an average of 54.1% following 17 months when compared to placebo. The data also confirmed the strong safety profile of inclisiran, and revealed that 99% of patients treated with inclisiran experienced a ≥30% reduction in LDL-C levels (placebo-adjusted).

Although efficacious and cost-effective lipid-lowering statins are available for patients with dyslipidemia, a proportion of patients cannot reach recommended levels of low-density lipoprotein cholesterol (LDL-C). PCSK9 inhibitors have largely been limited to patients who are unable to lower LDL-C levels with conventional lipid-lowering therapies, despite the need for additional treatments to address this gap in therapy. This has largely been due to their initial high price tags and payer restrictions, but they continue to face an uphill battle despite their developers cutting US net prices of both drugs, improving drug administration, and filing for new indications to promote use in high-risk patients.

In order to compete against Praluent and Repatha, Novartis may end up undercutting their prices with a cheaper inclisiran. However, if that strategy is taken, only a minimal price cut is expected, as inclisiran has a strong clinical profile along with a preferable dosing schedule. Novartis will also need to finish its cardiovascular outcomes study, ORION-4, which has been delayed due to the Covid-19 crisis, in order to close the competitive advantage held by both Praluent and Repatha; the two drugs have already completed outcome studies of their own, ODYSSEY and FOURIER, respectively. Despite the delays in Novartis’ ORION-4 study, GlobalData expects that inclisiran’s launch and uptake will be strong, as it has the opportunity to bypass some of the pushback that the PCSK9 inhibitors received revolving around high cost and reimbursement issues.