Advances in Non-Statin Therapies for Dyslipidemia, with Christie Ballantyne, MD

For decades, statin therapy has, and continues to, sit at the head of the table in conversations surrounding the management of dyslipidemia and atherosclerotic cardiovascular disease (ASCVD) risks. However, some patients, as a result of statin intolerance or inadequate response to therapy, require additional means to achieve a more optimal lipid profile.

Advances in non-statin therapy, both available and those still in development, was the subject of a presentation delivered at the Family Heart Foundation’s 2024 Family Heart Global Summit by leading cardiologist and trialist Christie Ballantyne, MD, professor of Medicine and chief of Cardiology and Cardiovascular Research at Baylor College of Medicine.

During his presentation, Ballantyne called attention to a number of underutilized breakthroughs in nonstatin therapy to occur during the last decade, including PCSK9 inhibitors, bempedoic acid, and inclisiran, which have received endorsements for use in the management of hypercholesterolemia by the American College of Cardiology and American Heart Association since 2018. Ballantyne also touched upon the role of ezetimibe, which, unlike the aforementioned agents and classes, earned approval from the US Food and Drug Administration (FDA) more than 20 years ago.¹

The medical community began to welcome PCSK9 inhibitors into treatment algorithms beginning in July 2015 with the FDA approval of alirocumab (Praluent) as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or established ASCVD who require additional lowering of LDL-C. The initial indication allowed for twice-monthly dosing. Less than 2 months later, evolocumab (Repatha) became the second member of the PCSK9 inhibitor class.^2,3

In February 2020, the community celebrated another groundbreaking approval for a non-statin therapy in bempedoic acid, a first-in-class ATP citrate lyase inhibitor. Approved as a monotherapy (Nexlizet) and in combination with ezetimibe (Nexletol) as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with HeFH or established ASCVD who require additional lowering of LDL-C. The approval marked the first for an oral, non-statin therapy since approval of ezetimibe in 2002. In 2024, the FDA expanded indications for bempedoic acid to included cardiovascular risk reduction and expanded LDL-C lowering in both primary and secondary prevention patients.^4,5

In December 2021, with support from a trio of phase 3 trials, inclisiran (Leqvio) received approval from the FDA as an adjunct to diet and maximally tolerated statin therapy for adults with HeFH or established ASCVD who require additional lowering of LDL-C. With the approval, patients and providers were given the ability to reduce LDL-C with administration occurring just once every 6 months after 2 initial loading doses. In 2023, the FDA approved a label expansion allowing for earlier use in patients with elevated LDL-C who have an increased risk of cardiovascular disease.^6,7

Relevant disclosures for Ballantyne include Arrowhead, AstraZeneca, Eli Lilly and Company, Abbott Diagnostics, NewAmsterdam, and others.

References:

1. Ballantyne C. Recent Advances in Non-Statin LDL Lowering Therapies. Presented at: 2024 Family Heart Global Summit. September 22-24, 2024.
2. Regeneron Pharmaceuticals Inc. Regeneron and Sanofi announce FDA approval of Praluent® (alirocumab) injection, the first PCSK9 inhibitor in the U.S., for the treatment of high LDL cholesterol in adult patients. Regeneron Pharmaceuticals Inc. July 15, 2024. Accessed September 27, 2024. https://investor.regeneron.com/news-releases/news-release-details/regeneron-and-sanofi-announce-fda-approval-praluentr-alirocumab.
3. Amgen. FDA approves Amgen’s new cholesterol-lowering medication RepathaTM (evolocumab). Amgen. August 27, 2015. Accessed September 27, 2024. https://www.amgen.com/newsroom/press-releases/2015/08/fda-approves-amgens-new-cholesterollowering-medication-repatha-evolocumab.
4. Esperion Therapeutics, Inc. Esperion announces FDA approval of NEXLETOLTM (bempedoic acid) tablet, an oral, once-daily, non-statin LDL-cholesterol lowering medicine. Esperion Therapeutics, Inc. February 21, 2020. Accessed September 27, 2024. https://esperion.gcs-web.com/news-releases/news-release-details/esperion-announces-fda-approval-nexletoltm-bempedoic-acid-tablet.
5. Esperion Therapeutics, Inc. U.S. FDA approves broad new labels for NEXLETOL® and NEXLIZET® to prevent heart attacks and cardiovascular procedures in both primary and secondary prevention patients, regardless of statin use. Esperion Therapeutics, Inc. March 22, 2024. Accessed September 27, 2024. https://www.esperion.com/news-releases/news-release-details/us-fda-approves-broad-new-labels-nexletolr-and-nexlizetr-prevent.
6. Novartis. FDA approves Novartis Leqvio® (Inclisiran), first-in-class Sirna to lower cholesterol and keep it low with two doses a year. Novartis. December 22, 2021. Accessed September 27, 2024. https://www.novartis.com/news/media-releases/fda-approves-novartis-leqvio-inclisiran-first-class-sirna-lower-cholesterol-and-keep-it-low-two-doses-year.
7. Novartis. US FDA approves expanded indication for Novartis Leqvio® (Inclisiran) to include treatment of adults with high LDL-C and who are at increased risk of heart disease. Novartis United States of America. July 10, 2023. Accessed September 27, 2024. https://www.novartis.com/us-en/news/media-releases/us-fda-approves-expanded-indication-novartis-leqvio-inclisiran-include-treatment-adults-high-ldl-c-and-who-are-increased-risk-heart-disease.