A novel monoclonal antibody identified in a new study dramatically lowered circulating LDL cholesterol by 40 percent to 72 percent, a development with 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 research presented today at the American College of Cardiology's 61st Annual Scientific Session.
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-center, 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."
Dr. McKenney said the results surprised him, "Statins are good medicines and getting a 70 percent reduction on top of them is remarkable."
The SAR236553/REGN727 antibody was discovered two years ago, and these are the first Phase II results for an anti-PCSK9 antibody to be presented. Dr. McKenney said a longer study is needed to establish the long-term safety of the antibody, but the results from this trial were promising, with only one adverse reaction reported.
"This is a very hopeful step in the treatment of heart disease in this country," said Dr. McKenney.
This study was funded by Sanofi US, Bridgewater, N.J., and Regeneron Pharmaceuticals, Tarrytown, N.Y. Dr. McKenney reports that he is an employee of a research company that has received research funding from Regeneron and Sanofi.
The study will be simultaneously published in the Journal of the American College of Cardiology and will be published online at the time of presentation.
Dr. McKenney will be available to the media on Monday, March 26 at 12:15 p.m. in Media Room 1, McCormick Place N, Level 1, Hall C1.
Dr. McKenney will present the study "A Randomized, Double-blind, Placebo-controlled Trial of the Safety and Efficacy of a Monoclonal Antibody to Proprotein Convertase Subtilisin/Kexin Type 9 Serine Protease, REGN727/SAR236553, in Patients with Primary Hypercholesterolemia" on Monday, March 26 at 10:30 a.m. in McCormick Place North: Main Tent.
About the American College of Cardiology
The American College of Cardiology (www.cardiosource.org) is a 40,000-member nonprofit medical society comprised of physicians, surgeons, nurses, physician assistants, pharmacists and practice managers. The College transforms cardiovascular care and improves heart health as it supports and advocates for quality improvement, patient-centered care, payment innovation and professionalism. The ACC bestows credentials upon cardiovascular specialists who meet its stringent qualifications and leads the formulation of health policy, standards and guidelines. It provides professional education, supports and disseminates cardiovascular research, and operates national registries to measure and promote quality.
The ACC's Annual Scientific Session brings together cardiologists and cardiovascular specialists from around the world each year to share the newest discoveries in treatment and prevention.
Beth Casteel | EurekAlert!
Study tracks inner workings of the brain with new biosensor
16.08.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn
Foods of the future
15.08.2018 | Georg-August-Universität Göttingen
There are currently great hopes for solid-state batteries. They contain no liquid parts that could leak or catch fire. For this reason, they do not require cooling and are considered to be much safer, more reliable, and longer lasting than traditional lithium-ion batteries. Jülich scientists have now introduced a new concept that allows currents up to ten times greater during charging and discharging than previously described in the literature. The improvement was achieved by a “clever” choice of materials with a focus on consistently good compatibility. All components were made from phosphate compounds, which are well matched both chemically and mechanically.
The low current is considered one of the biggest hurdles in the development of solid-state batteries. It is the reason why the batteries take a relatively long...
New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference
Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
17.08.2018 | Event News
08.08.2018 | Event News
27.07.2018 | Event News
20.08.2018 | Information Technology
20.08.2018 | Life Sciences
20.08.2018 | Information Technology