The potential usage of small interfering RNA agent, Olparisan, in treating elevated lipoprotein(a)
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Reviewed by Dat Tien Nguyen, B.A, ScM.
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Posted on November 30th, 2022
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Previous studies had reported on the causal relationship between elevated lipoprotein(a) - LP(a) - level and diseases such as atherosclerosis & calcific valvular aortic stenosis. However, there is currently no therapeutic agent approved to lower lipoprotein(a) concentration. LP(a) concentration is dependent on the expression of the LPA gene, and Olpasiran is a small interfering RNA (siRNA) that can interfere with its LPA transcription. Results from a study investigating the effect of Olpasiran on LP(a) level had recently been published.
The phase 2 clinical trial was performed by Thrombolysis in Myocardial Infarction (TIMI) Study Group at Brigham and Women’s Hospital and Harvard Medical School with the purpose of finding the examining the effectiveness and safety profile of Olpasiran; more importantly, this study help determine the most appropriate dose for future clinical researches. The study included 281 patients whose serum LP(a) concentration is above 150 nanomol per liter and have a history of atherosclerotic cardiovascular disease. Patients with lower renal function or active liver diseases were excluded from the study. These patients was randomly assigned into 5 intervention groups: 1) placebo; 2) 10 mg of Olpasiran every 12 weeks; 3) 75 mg of Olpasiran every 12 weeks; 4) 225 mg of Olpasiran every 12 weeks; 5) 225 mg of Olpasiran every 24 weeks. The appropriate interventions were administered subcutaneously for 48 weeks. The study reported that there was a dose-dependent reduction in lipoprotein(a) level. By the 36th week, those who receive 75 mg of Olpasiran experience a 97.4% drop in lipoprotein(a) level, and those who receive 225 mg of Olpasiran experience a 100% drop from baseline. Thus, the ideal dose is between 75 mg and 225 mg. By the end of the study (week 48), there is little difference in LP(a) level between the 36th and 48th week in groups with administration conducted every 12 weeks, but the LP(a) level of those who received 225 mg of Olpasiran every 24 weeks seems to increase between week 36 and 48 by approximately 15% of the baseline amount. In terms of safety, the rate of discontinuation is similar between the treatment and placebo group, and the frequency of liver-related adverse events, kidney-related adverse events, thrombocytopenia, and peripheral neuropathy are also similar. The only side effect that is more common in those who have received Olpasiran was pain at the site of injection. These findings are promising, it seems like Olpasiran can be an effective therapeutic agent with little unwanted effect. However, for the follow up studies, researchers should examine the direct clinical impact of Olpasiran on preventing cardiovascular accidents.
The phase 2 clinical trial was performed by Thrombolysis in Myocardial Infarction (TIMI) Study Group at Brigham and Women’s Hospital and Harvard Medical School with the purpose of finding the examining the effectiveness and safety profile of Olpasiran; more importantly, this study help determine the most appropriate dose for future clinical researches. The study included 281 patients whose serum LP(a) concentration is above 150 nanomol per liter and have a history of atherosclerotic cardiovascular disease. Patients with lower renal function or active liver diseases were excluded from the study. These patients was randomly assigned into 5 intervention groups: 1) placebo; 2) 10 mg of Olpasiran every 12 weeks; 3) 75 mg of Olpasiran every 12 weeks; 4) 225 mg of Olpasiran every 12 weeks; 5) 225 mg of Olpasiran every 24 weeks. The appropriate interventions were administered subcutaneously for 48 weeks. The study reported that there was a dose-dependent reduction in lipoprotein(a) level. By the 36th week, those who receive 75 mg of Olpasiran experience a 97.4% drop in lipoprotein(a) level, and those who receive 225 mg of Olpasiran experience a 100% drop from baseline. Thus, the ideal dose is between 75 mg and 225 mg. By the end of the study (week 48), there is little difference in LP(a) level between the 36th and 48th week in groups with administration conducted every 12 weeks, but the LP(a) level of those who received 225 mg of Olpasiran every 24 weeks seems to increase between week 36 and 48 by approximately 15% of the baseline amount. In terms of safety, the rate of discontinuation is similar between the treatment and placebo group, and the frequency of liver-related adverse events, kidney-related adverse events, thrombocytopenia, and peripheral neuropathy are also similar. The only side effect that is more common in those who have received Olpasiran was pain at the site of injection. These findings are promising, it seems like Olpasiran can be an effective therapeutic agent with little unwanted effect. However, for the follow up studies, researchers should examine the direct clinical impact of Olpasiran on preventing cardiovascular accidents.