In this study, patients at very high CV risk who were unable to reach their desired goal of an LDL below 70 mg/dL despite maximum tolerated statin doses were randomized 2:1 to alirocumab at 75 mg once every 2 weeks or oral ezetimibe (Zetia) at its approved dose of 10 mg/day as an active comparator. Each participant also received placebo therapy.
By week 24, patients on alirocumab plus high-dose statin averaged a 51% reduction in LDL compared to baseline, versus a 21% reduction with ezetimibe plus statin. These effects were maintained at 1 year, with no evidence of tolerance.
Of patients on alirocumab, 77% achieved an LDL goal of less than 70 mg/dL at week 24, compared with 45% on ezetimibe. In addition, 60% of the alirocumab group had an LDL below 50 mg/dL, as did 15% on ezetimibe.
The study design called for patients in the alirocumab group who still had an LDL above 70 mg/dL at week 12 to be uptitrated from 75 mg to 150 mg every 2 weeks. But only 20% of patients needed to do so, according to Dr. Cannon, professor of medicine at Harvard University, Boston.
Will high-risk patient adhere long-term to treatment by self-injection? Dr. Cannon thinks so. He noted that 85% of patients in ODYSSEY COMBO II remained adherent to the biweekly self-injection protocol through 1 year.
“That has been a very pleasant surprise,” the cardiologist said. “The notion of injections for cholesterol management is foreign. It was a big surprise to us that patients really did it.”
‘Great news’ from alirocumab
The alirocumab results in the heterozygous familial hypercholesterolemia trials are “great news for patients with this disease,” discussant Dr. Robert M. Califf said. He noted that recent estimates put the prevalence of heterozygous familial hypercholesterolemia at roughly 1 in 250 persons in the general population, making the genetic disorder considerably more common than most physicians realize.
“These are people who have a terrible disease where a massive reduction in LDL, it seems to me, is clearly worthwhile,” commented Dr. Califf, professor of medicine and vice chancellor for clinical and translational research at Duke University in Durham, N.C.
As for Dr. Robinson’s ODYSSEY LONG TERM data showing a 54% reduction in major CV events, he said “It’s alluring. It looks great. It looks fantastic. And it sets up the large events trial. The only caution out of all of this from my perspective is that any study with less than 100 events is something that should be regarded with great interest but is not definitive.”
If approved, alirocumab could see widespread use, especially if the ODYSSEY OUTCOMES results prove positive. After all, heterozygous familial hypercholesterolemia is now recognized to be one of the most common of all inherited diseases. And Dr. Cannon said that in clinical trials in post-acute coronary syndrome patients placed on high-dose statins, it’s common for only about 40% to achieve an LDL level below 70 mg/dL. In clinical practice, the rate is probably even lower.*
“Down the line I think this level of LDL lowering is needed very badly. To get high-risk patients who have high cholesterol despite maximally dosed statins or statin-intolerance down to an LDL level of 50 mg/dL would be a pretty good thing. This will be applicable to millions of patients,” he predicted.*
Dr. Robinson said that at the American Heart Association meeting this November she and her ODYSSEY LONG TERM coinvestigators plan to present subgroup analyses looking at alirocumab efficacy and safety in patients with achieved LDL levels below 25 and even 15 mg/dL.
Dr. Robinson, Dr. Cannon, and Dr. Farnier reported receiving research grants and consultants’ fees from Sanofi and Regeneron as well as other pharmaceutical companies. Dr. Califf reported having no financial conflicts.
bjancin@frontlinemedcom.com
*CORRECTION: An earlier version of this story misattributed these statements.