Evolocumab safe, effective in various patient populations

CHICAGO — New data on evolocumab presented at the American Heart Association Scientific Sessions yielded positive data for the lipid-lowering and safety profiles of the PCSK9 inhibitor.

Among the findings presented, evolocumab (Amgen) was associated with reduced lipoprotein(a) at 64 weeks; patients who achieved very low LDL levels while treated with evolocumab had a similar safety and tolerability profile compared with those who achieved higher LDL levels; and the drug was associated with lower LDL in patients with homozygous familial hypercholesterolemia.

Reduction in Lp(a)

Frederick J. Raal, MD, PhD, and colleagues conducted a pooled analysis of 3,278 patients from phase 2, phase 3 and open-label studies to assess whether evolocumab was associated with reduction in Lp(a), a lipoprotein associated with CVD risk for which there are few therapeutic options.

All patients completed a 12-week parent study and were followed for an additional 52 weeks after being re-randomly assigned to evolocumab plus standard of care or standard of care alone.

At the end of the parent study, patients taking evolocumab 140 mg every 2 weeks had a reduction in Lp(a) of –24.7 nmol/L compared with a gain of 4.4 nmol/L for controls, and those taking evolocumab 420 mg every month had a reduction in Lp(a) of –23.3 nmol/L compared with a gain of 4.9 nmol/L for controls (P<.001 for both), Raal, director of the Carbohydrate and Lipid Metabolism Research Unit at the University of Witwatersrand in Johannesburg, and colleagues found.

In the extension phase, mean changes in Lp(a) were consistent with the results from the parent study, whereas Lp(a) reductions correlated with percent reductions in LDL (Spearman’s correlation coefficient for parent study=0.49; P<.001; Spearman’s correlation coefficient for extension phase=0.38; P<.001), according to the researchers.

Very low LDL levels not harmful

Lowering LDL to <40 mg/dL with evolocumab was not associated with any excess safety or tolerability issues, Michael J. Koren, MD, from the Jacksonville Center for Clinical Research in Florida, and colleagues reported.

Koren and colleagues compared adverse events and lab abnormality rates at 52 weeks in 1,012 patients who achieved LDL <40 mg/dL (99.3% of whom were treated with evolocumab) and 1,187 patients who did not (38.9% of whom were treated with evolocumab) in the DESCARTES and OSLER-1 studies.

Both groups had comparable rates of at least one adverse event (<40 mg/dL group, 77.8%; ≥40 mg/dL group, 78.2%) and serious adverse events (<40 mg/dL group, 6.3%; ≥40 mg/dL group, 7.3%). Patients with very low LDL were more likely to have isolated elevated bilirubin above two times the upper limit of normal (0.9% vs. 0.2%), but less likely to have elevation of transaminases above three times the upper limit of normal (0.8% vs. 1.9%) compared with patients with higher LDL, the researchers found.

Benefit in homozygous familial hypercholesterolemia

Evan A. Stein

In a subgroup analysis of patients with homozygous familial hypercholesterolemia enrolled in the TAUSSIG study who were receiving lipid apheresis (n=37), Evan A. Stein, MD, PhD, and colleagues found that evolocumab was associated with LDL reduction in that population.

Patients received evolocumab 420 mg and apheresis biweekly, but after 12 weeks could be changed to evolocumab 420 mg monthly at investigator discretion.

Mean baseline LDL was 275 mg/dL, mean change in LDL at 12 weeks was –34 mg/dL (–17%) and mean change in LDL at 24 weeks was –48 mg/dL (–20%), Stein, voluntary professor of laboratory medicine at University of Cincinnati and director of the Metabolic and Atherosclerosis Research Center in Cincinnati, and colleagues reported.

Four patients stopped or reduced the frequency of apheresis after achieving a mean change in LDL of –73 mg/dL (–49%), but the three patients with LDL receptor negative mutations in both alleles did not have significant changes in LDL, the researchers found.

While 16 patients reported 85 adverse events, only one serious adverse event was reported, according to the researchers. – by Erik Swain

For more information:

Koren MJ. Abstract #16865.

Raal FJ. Abstract #15743.

Stein E. Abstract #17016. All presented at: American Heart Association Scientific Sessions; Nov. 15-19, 2014; Chicago.

Disclosure: The studies were funded by Amgen. Koren reports financial ties with Amgen, Pfizer and Sanofi/Regeneron. Raal reports financial ties with Amgen, AstraZeneca, Pfizer and Sanofi/Regeneron. Stein reports financial ties with Adnexus Therapeutics, Amgen, Genentech, Genzyme, Isis Pharmaceuticals and Sanofi/Regeneron.