Antibody injection may help cut bad cholesterol
Washington: Scientists have identified a novel monoclonal antibody that can significantly lower circulating LDL cholesterol by 40 percent to 72 percent.
The development shows potential to provide a new option for patients who are resistant to cholesterol-lowering drugs such as statins or to the current standard of care, according to the research.
The Scientific Session, the premier cardiovascular medical meeting, brings cardiovascular professionals together to further advances in the field.
The traditional statin therapy used by millions of Americans lowers LDL cholesterol – the “bad” cholesterol that leads to plaque build-up in the arteries and subsequently heart disease – by inhibiting the production of cholesterol in liver cells, causing an increase in the number of LDL receptors on the cell surface.
These receptors grab LDL circulating in the blood and deliver it into the liver, where it is subsequently processed and flushed out of the body.
About one in five people with high low-density lipoprotein (LDL) are resistant to cholesterol-lowering drugs such as statins, and for many others the current standard of care does not lower cholesterol enough.
A recent discovery showed that statin therapy stimulates the production of PCSK9, an enzyme that leads to the destruction of LDL receptors. The present study tested SAR236553/REGN727, a monoclonal antibody that binds to PCSK9, blocking its effects and preventing the degradation of LDL receptors.
More LDL receptors mean more LDL is brought out of the blood into the liver, and circulating levels of LDL cholesterol decrease.
“We’ve known for 30 years that lowering LDL cholesterol with statins lowers the risk of heart disease and that the more you can lower LDL cholesterol, the greater reduction in that risk,” said James McKenney, PharmD, chief executive officer of National Clinical Research, and the study’s lead investigator.
“However, we know in some cases that even the best statin can’t get LDL cholesterol as low as it should be.”
This multi-centre, randomized trial looked at 183 patients who had an LDL cholesterol reading of 100 mg/dL or higher.
The patients had already been treated with atorvastatin for more than six weeks at stable doses of 10, 20 or 40 mg.
The participants were divided into six groups: a placebo control; three groups who received a subcutaneous injection of SAR236553/REGN727 every two weeks (Q2W) at doses of either 50, 100, or 150 mg; and two groups who received an injection of SAR236553/REGN727 at 200 or 300 mg every 4 weeks (Q4W), alternating with placebo shots at two weeks.
The study’s primary endpoint was the percentage LDL cholesterol reduction from baseline to after 12 weeks.
Dr. McKenney reported a remarkable dose-response to SAR236553/REGN727 injections. Circulating LDL cholesterol was lowered by 40 percent, 64 percent, and 72 percent in patients assigned to 50, 100, or 150 mg Q2W doses, respectively.
LDL cholesterol was reduced by 43 percent and 48 percent for patients who received 200 or 300 mg Q4W injections. The placebo group reported a 5 percent reduction of circulating LDL cholesterol.
“Our LDL cholesterol treatment goals were less than 100 or 70 mg/dL,” Dr. McKenney said.
“All of the participants receiving one of our doses met those goals.”
“Statins are good medicines and getting a 70 percent reduction on top of them is remarkable,” Dr. McKenney added.