Conference Coverage
LAS VEGAS – Evolocumab, an investigational antibody that inhibits PCSK9, reduces levels of low-density lipoprotein cholesterol in hypercholesterolemic patients who have dysglycemia or metabolic syndrome – without worsening glucose metabolism, in contrast to what has been seen with high-intensity statin therapy, a new analysis shows.
"LDL-C reduction is an important intervention for patients with dysglycemia or metabolic syndrome. This analysis suggests evolocumab can safely reduce LDL-C in these patients and could become a valuable tool in their care," lead investigator Dr. Robert R. Henry said in an interview prior to presenting the results at the annual meeting of the American Association of Clinical Endocrinologists.
"PCSK9 inhibitors are evolving as a novel and exciting class of medications that significantly reduce LDL-C. Patients with conditions like diabetes may greatly benefit from these treatments, particularly many of them [who] are unable to achieve their LDL targets or have difficulty with statin-associated side effects," he added.
But before this new class of drugs becomes available to clinicians, "I think there are still lots of studies to be done with evolocumab," said Dr. Henry, who is with the division of endocrinology and metabolism at the University of California, San Diego.
Dr. Robert Henry
"The efficacy is quite striking. Of course, it’s currently being evaluated in cardiovascular outcome trials whether evolocumab translates to reduced cardiovascular events. And there is a large study ongoing of about 22,500 high-risk cardiovascular patients who are being studied for cardiovascular outcomes. So in the future, assuming these studies are positive, there is, I guess, a good chance this will be available."
In an interview, session comoderator Dr. Edward S. Horton, vice president and director of clinical research at the Joslin Diabetes Center and professor of medicine at Harvard Medical School, both in Boston, commented, "That’s very impressive data, a 50% reduction in LDL cholesterol with this drug. I think those data are very exciting. The drug has to go through the whole development process, but if it holds up in longer, more detailed studies, I think it looks very promising."
"Right now, the other options are basically statins," Dr. Horton noted. "Statins are very, very effective, but a lot of people get side effects from the statins, particularly the myositis can be a major problem. So this may be a very good alternative for the people who don’t tolerate statins. The fact that it’s an injection once a month I think is not a big deal, rather than just an oral agent. Statins are easy to take – you just take your statin orally, but a lot of people have trouble with the statins. So I think it’s going to have a role."
The patients studied were participants in the Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER), an extension trial in which patients from four phase II studies of evolocumab were randomized 2:1 to open-label monthly subcutaneous evolocumab plus standard of care or to standard of care alone for 1 year.
Results for the entire trial population, reported previously, showed that evolocumab was safe, well tolerated, and efficacious (Circulation 2014;129:234-43).
The new analysis, which additionally looked at impact on glucose metabolism in the subset with metabolic perturbations, was based on 109 patients with type 2 diabetes, 134 with impaired fasting glucose, and 425 with metabolic syndrome, some of whom had more than one condition.
Evolocumab was associated with an LDL-C reduction of 47% in patients with type 2 diabetes, 51% in those with impaired fasting glucose, and 52% in those with metabolic syndrome – this compared with no change in their counterparts given standard of care alone. (It was 53% with evolocumab in trial patients who did not have any of metabolic perturbations.)
"Reductions were comparable to those observed in OSLER patients without these conditions," pointed out Dr. Henry.
The drug was also associated with improvement relative to standard care in levels of HDL cholesterol, triglycerides, and lipoprotein(a) that were again similar to those seen in trial patients who did not have these conditions.
Importantly, evolocumab was not associated with any significant changes in fasting plasma glucose or glycated hemoglobin levels relative to standard of care.
The combined evolocumab group and standard of care group had essentially the same rates of adverse events (78% and 72%) and serious adverse events (8% and 6%). Rates of serious laboratory abnormalities such as marked elevation of creatine kinase were low and similar as well.
The trial was sponsored by Amgen. Dr. Henry disclosed that he has affiliations with Amgen and Sanofi.