Antibody injection lowers LDL, adding to effectiveness of statin therapy
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.
Provided by American College of Cardiology
- Monthly shot lowers cholesterol 66 percent: study Mar 26, 2012 | not rated yet | 0
- Statin alternative looks promising in early trials Mar 22, 2012 | not rated yet | 0
- Low 'bad' cholesterol levels may be linked to cancer risk Mar 26, 2012 | not rated yet | 0
- Cholesterol-lowering drugs reduce risk of stroke, heart attack May 02, 2007 | not rated yet | 0
- Adding ezetimibe to atorvastatin improves lipid control Oct 27, 2009 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Bubbles in a Pre-Boiling/Boiling pot of water
2 hours ago How is it that bubbles form on the bottom of a surface of a pot of boiling water? I think that there is probably an elementary answer to this...
Assumptions of Griffith's fracture theory
12 hours ago Any experts on Griffith's fracture theory? I am studying the subject and I am having hard time finding out if the theory is valid for all possible...
Current leading voltage or vice versa concept
14 hours ago Hello, I was wondering if there is a conceptual explanation for when current leads voltage or vice versa for capacitors or inductors with AC...
Angular Frequency of AC voltage
17 hours ago Hello, I am wondering, what is the physical interpretation of the angular frequency of AC voltage? I don't see the physicality of what the angle...
Modeling Rigid Body - Unsure about Euler angles and angular velocity
17 hours ago I'm modeling a single 3D rigid body in preparation for some more complicated modeling in order to gain a better understanding of Euler angles, the...
Function for a bullet's path
19 hours ago I've been mulling this over all weekend, and I've decided to get some help on this. The problem is writing a function to describe a bullet's path....
- More from Physics Forums - Classical Physics
More news stories
(Medical Xpress)—In a recent subgroup analysis of the largest blood pressure treatment trial in history, University of Alabama at Birmingham (UAB) researchers found that women and men react the same to ...
Cardiology 6 hours ago | 5 / 5 (1) | 0
Over the past few decades, scientists have developed many devices that can reopen clogged arteries, including angioplasty balloons and metallic stents. While generally effective, each of these treatments ...
Cardiology 7 hours ago | 4.8 / 5 (4) | 0 |
(Medical Xpress)—Cardiologists have identified a trio of biomarkers that may predict which patients with heart disease have a high risk of heart attack or death in the next two years.
Cardiology 8 hours ago | 4 / 5 (1) | 0 |
Hospitals with the highest rates of cardiac arrests tend to have the poorest survival rates for those cases, new University of Michigan Health System research shows.
Cardiology 23 hours ago | not rated yet | 0
A clinical trial of 75 patients hospitalized with acute decompensated heart failure (ADHF) suggests that aggressive fluid and sodium restriction has no effect on weight loss or clinical stability at three days but was associated ...
Cardiology 23 hours ago | not rated yet | 0
Researchers at USC have found that a class of pharmaceuticals can both prevent and treat Alzheimer's Disease in mice.
48 minutes ago | not rated yet | 0 |
(Medical Xpress)—Native peoples in regions where cameras are uncommon sometimes react with caution when their picture is taken. The fear that something must have been stolen from them to create the photo ...
3 hours ago | 4 / 5 (3) | 0 |
(Medical Xpress)—Despite spending billions of dollars on research and development, drug companies have been unable to come up with effective treatments for dementia and Alzheimer's Disease (AD). Now, A. ...
1 hour ago | 4.7 / 5 (3) | 0 |
Australian scientists have charted the path of insulin action in cells in precise detail like never before. This provides a comprehensive blueprint for understanding what goes wrong in diabetes.
3 hours ago | 4.5 / 5 (2) | 0 |
Children with autism showed significant improvement after six months of simple sensory exercises at home using everyday items such as scents, spoons and sponges, according to UC Irvine neurobiologists.
1 hour ago | not rated yet | 0 |
Researchers at Emory University have identified a protein that stimulates a pair of "orphan receptors" found in the brain, solving a long-standing biological puzzle and possibly leading to future treatments for neurological ...
3 hours ago | not rated yet | 0 |