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At AHA 2022, Dr. Ray discusses the findings from the phase II open-label extension trial and highlights other important trial data for lipidologists.
Current data suggest that elevated low-density lipoprotein cholesterol (LDL-C) is the most readily modifiable risk factor in patients with atherosclerotic cardiovascular disease (ASCVD).
New findings from the ORION-3 trial indicated twice-yearly inclisiran (Leqvio) as a complement to statin therapy provided effective and sustained reductions in LDL-C over four years of treatment.
The phase II open-label extension trial showed LDL-C level reduction was sustained over the four-year study period with an average 47.5% reduction in LDL-C from baseline to Day 210 and a time-averaged reduction in LDL-C of 44.2% over the four-year period.
The research was presented at the American Heart Association (AHA) Scientific Sessions 2022 in Chicago.
In an interview with HCPLive, presenting author Kausik Ray, MD, Imperial College London addressed the purpose of the study in determining the difference between the investigator’s hypothesis on the usage of inclisiran and the reality of the treatment. They set out to determine the feasibility of the twice-twice yearly dosing regimen and what LDL-C lowering it is able to achieve.
“Importantly, because of the long duration of action of the drug, you have to remember that repeatedly using this mechanism of action, there were a lot of unknowns,” Ray said. “Nobody's ever tested any of the type of therapies using this approach this fall. So it answered not just for this, but for other therapies as well.
When observing the peak effect, around nine months into the second year of receiving any inclisiran, data show the effect was approximately 47.5% lowering in LDL. As it is not placebo-corrected, it is what was seen in the previous studies and with placebo correction, it may have been over 50%, according to Ray.
But more importantly, year-over-year, Ray noted that with two doses, patients could achieve about 45% lowering in LDL. Over the window of four years, with eight or nine doses, patient could achieve 44% lowering.
“Now, imagine patients going out to 10 years that have taken 20 doses,” Ray said. “But in that 10 year window, you can say we can lower your LDL with two doses a year, for example, and achieve an LDL lowering of 45%. So we saw that, and we show sustained, robust reductions with this approach.”
Ray additionally noted that investigators saw no extra safety signals, with only mild adverse events. He added that inclisiran can maintain those robust reductions through that convenient twice a year dosing regimen.
In the latter half of the interview, Ray discussed the biggest trial data for lipidologists and what primary care practitioners may need to know about the biggest advancements or evolutions in lipid management.