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ODYSSEY LONG TERM hints at reduction in CV events with alirocumab
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BARCELONA, Spain — Long-term results indicate that in addition to reducing cholesterol on top of regular statin therapy, treatment with alirocumab also reduced the incidence of CV events.
The ODYSSEY LONG TERM trial included 2,341 patients with hypercholesterolemia (≥70 mg/dL at baseline) at high or very high CV risk, including those with heterozygous familial hypercholesterolemia (18%). Researchers randomly assigned each patient to receive a subcutaneous injection of alirocumab 150 mg every 2 weeks (n=1,553) or matching placebo (n=788). Both groups were also treated with maximally tolerated statin therapy and some patients received additional lipid-lowering therapy.
All patients have been followed for 52 weeks and follow-up is ongoing. Jennifer G. Robinson, MD, MPH, presented data at ESC Congress from a mean follow-up of 65 weeks.
“ODYSSEY LONG TERM is the largest and longest study of a PCSK9 inhibitor to report results to date, with approximately 1,900 patient-years of double-blind exposure to alirocumab,” Robinson, from the College of Public Health at University of Iowa, said during a press conference.
Jennifer G. Robinson
The primary endpoint was percent change from baseline to 24 weeks in LDL. The mean reduction was 61% for patients treated with alirocumab (Sanofi/Regeneron) compared with an increase of 0.8% for patients treated with placebo; the researchers calculated a mean difference vs. placebo of 61.9% (P<.0001). Seventy-nine percent of patients achieved a target LDL <70 mg/dL after treatment with alirocumab.
“ODYSSEY LONG TERM was primarily a safety trial,” Robinson said.
Safety results, including 52 weeks of therapy for all patients and 78 weeks for about 600 patients, showed a similar rate of treatment-emergent adverse events in both groups (alirocumab, 78.6%; placebo, 80.6%). The most common adverse events were nasopharyngitis, upper respiratory tract infection and injection-site reactions. Adverse events were associated with study discontinuation in 6.2% of patients in the alirocumab group and 5.5% of patients in the placebo group.
The long-term study also assessed major CV events at 65 weeks. Results of a post-hoc safety analysis demonstrated a lower absolute event rate of major CV events in the alirocumab group vs. placebo (1.4% vs. 3%; P<.01); this translated to a relative risk reduction of 54% with alirocumab. The analysis used the same composite primary endpoint — cardiac death, MI, stroke and unstable angina requiring hospitalization — as the ongoing 18,000-patient ODYSSEY OUTCOMES trial, which is prospectively evaluating the potential of alirocumab to demonstrate CV benefit.
ODYSSEY LONG TERM “is the first PCSK9 inhibitor study to show a lower rate of major CV events in a post-hoc analysis,” Robinson said. – by Katie Kalvaitis
For more information:
Robinson JG. Hot Line II. Coronary Artery Disease and Lipids. Presented at: the European Society of Cardiology Congress; Aug. 30-Sept. 3, 2014; Barcelona, Spain.
Disclosure: The study was funded by Sanofi/Regeneron. Robinson reports receiving research grants from Amarin, Amgen, AstraZeneca, Daiichi Sankyo, Genentech/Hoffman La Roche, GlaxoSmithKline, Merck, Sanofi/Regeneron and Zinfandel/Takeda, and consulting/advisory board work for Amgen, Hoffman La Roche, Merck, Pfizer and Sanofi.
Perspective
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Christie M. Ballantyne, MD
It is nice to see longer-term data in large groups of patients. There were a number of large studies of alirocumab presented at the ESC Congress and they all look the same. Now, we have more than a year of therapy and larger groups of patients who were treated. We saw a sustained effect on LDL and the post-hoc analysis results were encouraging. There are a lot of limitations [to the observed reduction in CV events], but nonetheless it was encouraging to see some reduction in hard CV events. From a safety perspective, we want to make sure that we aren’t hurting people [with new therapies]. Also encouraging is that the companies [developing PCSK9 inhibitors] have taken an approach similar to what we have seen with diabetes drugs. They are doing a number of studies showing efficacy in the correct patient populations, but what is very nice to see is the outcomes trials already in progress. Alirocumab has a large outcomes study, evolocumab (Amgen) has a large outcomes study and bococizumab (Pfizer) has two outcomes studies.
Taken together, it is good that we are seeing safety, tolerability, sustained LDL reduction and the first hint that we might be delivering on something promising in terms of CV events.
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