Although treatment options for hypercholesterolemia have diversified in recent years with the introduction of targeted therapies, new strategies are needed to reduce the residual risk of cardiovascular events. Increasing evidence points to a role for lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis. Even though it has been discovered for over 60 years, there are currently no approved treatments for lowering lp(a).
For the first time, an oral therapy, muvalaplindetermined reduction of lipoprotein (a) by up to 65%, according to a phase 1 study presented at the Congress of the European Society of Cardiology and published in JAMA. Effects were seen 24 hours after the first dose and significant reductions were achieved with repeated dosing, with 93% of participants able to achieve Lp(a) values below 50 mg/dl. No clinically relevant adverse effects were recorded.
Lipoprotein(s) it is similar to LDL cholesterol, but classic lipid-lowering drugs such as statins do not have the same effectiveness. Among the therapies available on the market, the most effective are PCSK9 inhibitors, which, however, have a modest effect on this marker, necessitating new therapeutic approaches. Lp(a) values are strongly influenced by the genetic component, therefore, they cannot be controlled by diet, physical activity or lifestyle changes. Lp(a) is a complex plasma lipoprotein, composed of LDL-cholesterol and an apoB particle. Plasma values can be determined only once in a lifetime.
Lp(a) includes a lipoprotein similar in composition to LDL-cholesterol: Lp(a) – C and a glycoprotein, apolipoproteina (a), attached to the apoB component of the LDL-C structure. Plasma Lp(a) levels are genetically determined, with LPA being the main gene involved, followed by APOE and PCSK9. Photo Source – Journal of Clinical Medicine
Several therapeutic approaches are currently being explored to target lp(a) by decreasing hepatic synthesis of apo(a). Studies report an 80% reduction in lp(a) with use oligonucleotidelor antisens and by nearly 98% through therapies that work through interferența ARN. Both approaches involve injecting the treatment. Muvalaplin is an oral small molecule therapy that inhibits lp(a) formation by blocking the interaction between apo(a) and apo B100.
The phase I study evaluated whether muvalaplin can reach plasma concentrations sufficient to safely lower lp(a) levels without affecting the activity of plasminogen (an enzyme that breaks down fibrin, involved in dissolving blood clots). The randomized, double-blind study was conducted in the Netherlands and included 114 people. The main results obtained:
Muvalaplin reduces lp(a) within 24 hours of administration of the first dose, an effect that increases with repeated doses. The greatest reduction in lp(a) was 65% at doses of 100 mg or more on days 14 and 15. 93% of study participants who had elevated lp(a) achieved reduction in this marker below 50 mg/dl. Treatment did not influence LDL-c, HDL-c, triglycerides or ApoB or plasminogen values.
Pharmacological and safety data support further clinical research in a larger group of participants with elevated lipoprotein(a) values to determine the long-term effects of muvalaplin as well as to evaluate the cardiometabolic impact.
New data from the phase 2 study were also presented at the European Congress of Cardiology OCEAN(a)-DOSEabout olpasirana therapy that works through RNA interference and produces sustained effects in reducing Lp(a).
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2023-09-02 15:17:34
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