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
-
what is the distance traveled
2 hours ago
-
Image of a Convex Lens Cut in Half Horizontally
6 hours ago
-
Ray tracing throught optical system of thick lenses
6 hours ago
-
Faraday's law on circular wire
7 hours ago
-
Specific Exergy vs Specific Flow Exergy
8 hours ago
-
The Durability of Bone: Long Falls
17 hours ago
- More from Physics Forums - Classical Physics
More news stories
Costs to treat stroke in America may double by 2030
Costs to treat stroke are projected to more than double and the number of people having strokes may increase 20 percent by 2030, according to the American Heart Association/American Stroke Association.
Cardiology
3 hours ago |
not rated yet |
0
New blood-thinner measures may cut medication errors
Blood thinners are the preferred treatment option to prevent heart attacks, blood clots and stroke, but they are not without risk, and not just because of their side effects. These high-risk drugs, known as anticoagulants, ...
Cardiology
5 hours ago |
not rated yet |
0
Registry questions superiority of bivalirudin over heparin
Results from a large observational study reported at EuroPCR 2013 today question whether bivalirudin is superior to heparin in the absence of GPIIb/IIIa blockade, showing similar 30-day mortality in patients with non-ST segment ...
Cardiology
5 hours ago |
not rated yet |
0
Study shows low rate of late lumen loss with bioresorbable DESolve device
The DESolve bioresorbable coronary scaffold system achieves good efficacy and safety with low rates of late lumen loss and major coronary adverse events at six months, show first results from the pivotal DESolve Nx trial ...
Cardiology
5 hours ago |
not rated yet |
0
Biodegradable stent proves non-inferior to drug-eluting stent
The Orsiro stent, which is a novel stent platform eluting sirolimus from a biodegradable polymer, demonstrated non-inferiority to the Xience Prime everolimus-eluting stent for the primary angiographic endpoint of in-stent ...
Cardiology
21 hours ago |
5 / 5 (1) |
0
Enzyme-activating antibodies revealed as marker for most severe form of rheumatoid arthritis
In a series of lab experiments designed to unravel the workings of a key enzyme widely considered a possible trigger of rheumatoid arthritis, researchers at Johns Hopkins have found that in the most severe ...
Research offers promising new approach to treatment of lung cancer
Researchers have developed a new drug delivery system that allows inhalation of chemotherapeutic drugs to help treat lung cancer, and in laboratory and animal tests it appears to reduce the systemic damage ...
Researchers complete largest genetic sequencing study of human disease
Researchers from Queen Mary, University of London have led the largest sequencing study of human disease to date, investigating the genetic basis of six autoimmune diseases.
Slowing the aging process—only with antibiotics
Swiss scientists reveal the mechanism responsible for aging hidden deep within mitochondria—and dramatically slow it down in worms by administering antibiotics to the young.
Overeating learned in infancy, study suggests
In the long run, encouraging a baby to finish the last ounce in their bottle might be doing more harm than good.
Researchers analyse hunting behaviour of fish larvae in virtual reality
Moving objects attract greater attention – a fact exploited by video screens in public spaces and animated advertising banners on the Internet. For most animal species, moving objects also play a major ...