Research Highlights Long-Term Efficacy of PCSK9 Inhibitor
Jennifer Barrett, Associate Editor
New study data reinforce the long-term efficacy and safety of Amgen’s evolocumab (Repatha) in individuals at risk for heart attack and stroke, but an additional analysis highlights challenges associated with use of lipid-lowering therapies (LLTs) in these patients, according to a press release.
Evolocumab, which is a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, was approved in 2015 by the FDA as an adjunct to diet and other low-density lipoprotein- (LDL) lowering therapies, such as statins, in patients with primary hyperlipidemia and homozygous familial hypercholesterolemia, who require additional lowering of LDL cholesterol (LDL-C). Evolocumab is also indicated for adults with established cardiovascular disease to reduce the risk of heart attack, stroke, and coronary revascularization.
The Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER-1) is the longest duration study of a PCSK9 inhibitor to date, Amgen stated in the press release. The trial evaluated the safety and efficacy of evolocumab over 5 years in patients with hypercholesterolemia, including those with heterozygous familial hypercholesterolemia on background statin therapy and patients with statin intolerance. During the first year, patients received either evolocumab 420 mg monthly in addition to standard of care (SOC) or SOC alone for the remaining 4 years of the study.
Based on the results, long-term treatment with evolocumab was associated with robust and consistent reductions in LDL-C, with no increase in overall rates of adverse events over time and no neutralizing antibodies. According to the data, patients treated with evolocumab achieved a 59% reduction in mean LDL-C from baseline during the first year of treatment. The mean LDL-C reductions at years 2, 3, 4, and 5 were 56%, 57%, 56%, and 56%, respectively.
Additionally, adverse events were reported in 80%, 74%, 71%, 67%, and 65% of patients, respectively.
“These findings are consistent with those observed in the Repatha cardiovascular outcomes study (FOURIER) and other phase 3 trials, reinforcing Repatha’s role in the treatment of high-risk patients who are unable to achieve sufficient LDL-C reduction through other means,” David M Reese, MD, executive vice president of Research and Development at Amgen, said in a statement.
An analysis of data from the Getting to an Improved Understanding of Low-Density Lipoprotein and Dyslipidemia Management (GOULD) Registry reflected the underutilization of lipid-lowering therapies (LLTs) in patients at risk, as well as the need to educate patients on their treatment. The analysis included findings from interactive phone surveys with the lead physicians from each of the 120 US centers participating in the registry and 5006 patients.
According to the findings, investigators concluded that LLTs were underused among patients at high risk for cardiovascular events—those with LDL-C levels ≥70 mg/dL. The analysis showed that support for high-intensity statins and PCSK9 inhibitor use was at 75% among physicians, but the actual observed use was 50% and 10%, respectively. Additionally, physicians cited cost and hassle associated with prior authorization requirements as reasons for not prescribing. Among patients receiving LLT, more than 70% did not know the main goal of this treatment and nearly half were unaware of their total lipid levels, highlighting an educational gap. Data also showed that a large proportion of patients were unaware of their ASCVD risk, LDL-C levels, or therapy goals.
Despite the efficacy of PCSK9 inhibitors, the high cost of these medications can cause barriers to access. In October, Amgen announced it was reducing the price of evolocumab by 60% from its annual list price of $14,100. The manufacturer will continue to offer evolocumab at its original price, but is expected to discontinue the original cost by the end of 2020 or sooner.
These analyses were presented at the American Heart Association’s Scientific Sessions 2018 in Chicago.
Amgen Presents Results Highlighting The Long-Term Safety and Efficacy of Repatha® (Evolocumab) In The Longest Duration Study Of A PCSK9 Inhibitor To Date At AHA Scientific Sessions 2018 [news release]. Amgen’s website. https://www.amgen.com/media/news-releases/2018/11/amgen-presents-results-highlighting-the-longterm-safety-and-efficacy-of-repatha-evolocumab-in-the-longest-duration-study-of-a-pcsk9-inhibitor-to-date-at-aha-scientific-sessions-2018/. Accessed November 16, 2018.