PCSK9i siRNA therapy for lowering LDL-c levels approved by EC

The PCSK9 siRNA inclisiran has been approved in the EU for the treatment of adult patients with ASCVD, ASCVD-risk equivalents and heterozygous familial hypercholesterolemia (HeFH) with high LDL-c concentrations while receiving maximally tolerated, high-intensity LDL-c lowering therapy.

The approval is based on the positive results from the placebo-controlled ORION trials. For the primary endpoint of the ORION-11 phase III trial, the PSCK9 siRNA therapy resulted in a 50% reduction in LDL-c levels (P<0.0001) after 17 months and a time-adjusted (from 3 to 18 months) decrease in LDL-c concentration of 49% (P<0.0001) in ASCVD patients or ASCVD-risk equivalents. Similar results were obtained in HeFH patients with elevated levels of LDL-c despite maximally tolerated LDL-c lowering treatment. After an initial dose followed by one at 3 months, two doses a year of inclisiran are expected to support long-term adherence.

“Long-term exposure to persistently elevated LDL-c increases the risk of ASCVD, which may lead to a CV event . Inclisiran treatment provides an effective and sustained LDL-c reduction and will give an opportunity to change how elevated LDL-c is treated”, said professor Ulf Landmesser, director of Charité Center for Cardiovascular Diseases, Berlin, Germany. “With only two injection doses a year, this therapy is expected to circumvent the challenges of treatment adherence.”

Inclisiran is approved for the treatment of adults diagnosed with HeFH or non-familial hypercholesterolemia, or mixed dyslipidemia, who are either in combination with other LDL-c lowering therapies or without unable to reach their recommended LDL-c concentration goals according to the current guidelines. This siRNA therapy was well tolerated in the phase III trials, with injection site reactions among the most frequent adverse events.

Source: Press release Novartis, 11 December 2020