CHICAGO — A novel monoclonal antibody identified in a new study dramatically lowered circulating LDL by 40% to 72%, a development researchers said has 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.
The study tested SAR236553/REGN727 (Sanofi and Regeneron), a monoclonal antibody that binds to PCSK9, blocking its effects and preventing the degradation of LDL receptors.
The randomized, multicenter trial included 183 patients with an LDL level of ≥100 mg/dL. Patients had been treated with atorvastatin for more than 6 weeks at stable doses of 10 mg, 20 mg or 40 mg. Researchers divided patients into six groups:
- Placebo control.
- Three groups received a subcutaneous injection of the study drug every 2 weeks (Q2W) at doses of 50 mg, 100 mg, or 150 mg.
Two groups received an injection of the study drug at 200 mg or 300 mg every 4 weeks (Q4W), alternating with placebo shots at 2 weeks.
The study’s primary endpoint was the percentage LDL reduction from baseline to after 12 weeks. McKenney reported a remarkable dose-response to the injections. Circulating LDL was lowered by 40%, 64% and 72% in patients assigned to 50 mg, 100 mg or 150 mg Q2W doses, respectively. LDL was reduced by 43% and 48% for patients who received 200 mg or 300 mg Q4W injections.
“We were impressed with the additional reduction, considering the statin may already have reduced LDL by 40% to 50%,” James McKenney, PharmD, chief executive officer of National Clinical Research, said at a press conference at the American College of Cardiology’s 61st Scientific Sessions.
The placebo group had a 5% reduction of circulating LDL.
“Our LDL treatment goals were less than 100 mg/dL and 70 mg/dL, “McKenney said in a press release. “All of the participants receiving the 150 mg every 2 weeks dose met those goals.”
The SAR236553/REGN727 antibody was discovered 2 years ago, and these are the first phase 2 results for an anti-PCSK9 antibody to be presented.
“We are enthusiastic about this mechanism because it may be the next big step. This drug is quite powerful — as powerful, if not more so, than statins.”
McKenney said statins have consistently performed since their release to the market in the 1980s, but noted that this class of drugs is not without complications.
“Some people are left behind, even with the most powerful of statin therapies,” he said. “Some have difficulty getting a substantial reduction; others can’t tolerate higher doses. Clinicians have a difficult time figuring out what to do when this occurs.”
The researchers said a longer study is needed to establish the long-term safety of the SAR236553/REGN727 antibody, but results from this trial were promising, with only one adverse reaction reported. – by Rob Volansky
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Disclosure: Dr. McKenney is an employee of a research company that received research funding from Regeneron Pharmaceuticals and Sanofi. The study was funded by Regeneron Pharmaceuticals and Sanofi.
C. Noel Bairey Merz
This is very exciting. I am interested in seeing what happens as the researchers go forward with a phase 3 clinical trial. However, I’d say that it will be difficult to show additional benefit in getting LDL down from 100 mg/dL to 70 mg/dL in patients who are already being treated with a well-tolerated and moderately intense dose of a potent statin. They are going to have to randomize a large number of people. I’d say that the population they presented today would not have been the population that I would have selected for the trial. Another point is that these monoclonal antibodies are going to be quite expensive. Another question is: How many people are going to want to give themselves shots?
I think it will be a paradigm changer for people with familial hypercholesterolemia, a population that remains one in 20 of our MI victims. There are a lot of MI in this country, so it may be a game changer for them, especially for people who are statin-intolerant, which counts for about 15% of the people we would like to see start taking a statin.
– C. Noel Bairey Merz, MD
Cardiology Today Editorial Board member