In a study conducted by researchers at the Imperial College London, inclisiran––the first in a new class of gene-silencing drugs––has halved cholesterol levels in patients at risk of cardiovascular disease. The technique, known as RNA interference (RNAi) therapy, essentially “switches off” one of the genes responsible for elevated cholesterol levels. The results were published in the New England Journal of Medicine.
The researchers say that the twice-a-year treatment could be safely given with or without statins, depending on the patient’s needs. Eventually, inclisiran could help to reduce the risk of heart attacks and stroke related to hypercholesterolemia, they contend.
“We appear to have found a versatile, easy-to-take, safe treatment that provides sustained lowering of cholesterol levels and is therefore likely to reduce the risk of cardiovascular disease, heart attacks, and stroke,” said lead author Professor Kausik Ray. “These reductions are over and above what can already be achieved with statins alone or statins plus ezetemibe, another class of cholesterol-lowering drug.”
Statins are currently the standard treatment for patients with hypercholesterolemia, combined with exercise and healthy diet, as they reduce cholesterol levels in the blood and therefore help to prevent heart attacks and stroke. However, many patients are unable to tolerate the highest statin doses, or their cholesterol levels remain high despite receiving the maximum doses.
In the new phase 2 trial, the researchers gave either inclisiran or placebo to 497 patients with hypercholesterolemia who were at high risk of cardiovascular disease. The study participants were recruited from the United States, the United Kingdom, Canada, Germany, and the Netherlands. Most of these patients (73%) were already taking statins, and 31% were taking ezetimibe. Patients were excluded if they were taking monoclonal antibodies for cholesterol lowering.
The patients were given different doses of subcutaneous inclisiran or placebo, either in a single 300-mg dose or via a 300-mg dose on day one and another 300-mg dose at three months. The patients were followed up regularly for a subsequent eight months and were tested for blood cholesterol and adverse events.
The researchers found that the patients’ low-density lipoprotein cholesterol (LDL-C) levels had been reduced by up to 51% at just one month after receiving a single treatment of inclisiran.
In those given a single 300-mg dose, cholesterol levels were reduced by 42% at six months. In the matched placebo group, cholesterol levels had increased by 2% within that time frame. In those given two 300-mg doses, cholesterol levels were reduced by up to 53% at six months. Moreover, cholesterol levels had dropped for all patients in this group, and 48% had achieved cholesterol levels of less than 50 mL/dL.
In all of the inclisiran-treated patients, cholesterol levels remained lower for at least eight months. No additional adverse effects were seen in the active-treatment group compared with the placebo group.
The authors point out that because inclisiran acts on a different biological pathway than that of statins, the two drugs could likely be combined for the best results. The next step, they say, is to conduct an extended study, using more patients and for a longer period, to determine whether the reductions in cholesterol with inclisiran translate into a clinical reduction in heart attacks and strokes.
Source: Imperial College London; March 17, 2017.