Long term results for the investigational monoclonal antibody alirocumab, show that in addition to significantly reducing cholesterol on top of regular statin therapy, it also reduced the incidence of cardiovascular events, researchers reported in a Hot Line session today at ESC Congress 2014.
The ODYSSEY LONG TERM trial of alirocumab is the largest Phase 3 study, with the longest follow-up data for a new class of drugs called proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors.
Alirocumab is the first nonstatin that appears to reduce additional cardiovascular events on top of statin therapy, and this is very encouraging since previous trials of various lipid-lowering and other drugs have failed to find this,” said principal investigator Jennifer Robinson, MD, from the University of Iowa, Iowa City, IA, in the USA.
“Given the data available, alirocumab should prove a useful addition for lowering low density lipoprotein cholesterol (LDL-C) in high risk patients, including those with genetic high cholesterol or who cannot tolerate the recommended dose of statin.”
The study included 2431 patients (aged approximately 65 years) with high cholesterol who were either at high cardiovascular risk or who had heterozygous familial hypercholesterolemia (approximately 18%), an inherited disease for which current treatments often do not lower cholesterol adequately.
All study subjects had LDL-C levels of at least 1.81 mmol/L (70 mg/dL) at baseline, and were randomised to receive alirocumab (n=1553) 150 mg subcutaneously every two weeks for 78 weeks, or matching placebo (n=788).
In addition to study medication, all patients were also receiving a maximally tolerated stable statin dose with or without other lipid-lowering therapy (LLT) for at least four weeks prior to screening.
A first-step analysis showed that at 24 weeks, there was a mean LDL-C reduction from baseline of 61% for patients treated with alirocumab, while patients on placebo had an increase of 0.8% (P<0.0001).
In addition, by week 24, significantly more alirocumab-treated patients compared to those on placebo had reached the LDL-C goal of at least a 50% reduction from baseline (76% vs 2%, P<0.0001), or a level below 2.59 mmol/L (100 mg/dL) in high-risk patients and below 1.81 mmol/L (70 mg/dL) in very high-risk patients (81% vs 9%, P<0.0001).
Safety results, including 52 weeks of therapy for all patients, and 78 weeks for about 600 patients, showed that treatment-emergent adverse events (TEAEs) were similar in both arms, occurring in 78.6% and 80.6% of the alirocumab and placebo-treated patients, respectively, and leading to discontinuation in 6.2% and 5.5%, respectively.
There was also lower rate of adjudicated major cardiovascular events (cardiac death, myocardial infarction, stroke, and unstable angina requiring hospitalisation) in the alirocumab arm compared to placebo (p< 0.01).
“We still need to see the results of the ongoing long-term cardiovascular outcomes trial to determine whether alirocumab should be routinely added to statin therapy to further reduce cardiovascular risk in high risk patients,” noted Dr. Robinson.