Esperion Therapeutics has secured FDA alignment to proceed with Phase 3 clinical trials of bempedoic acid for pediatric patients with familial hypercholesterolemia, the company announced on March 20, 2025. The trials will evaluate both standalone bempedoic acid and its combination with ezetimibe in children with heterozygous and homozygous forms of the genetic condition.
The FDA's decision follows review of Phase 2 clinical data, which the agency deemed sufficient to advance the development program. Esperion plans to initiate the Phase 3 studies later this year, building on the orphan drug designation previously granted for bempedoic acid in homozygous familial hypercholesterolemia (HoFH).
"We are delighted to further advance the development of bempedoic acid for children with familial hypercholesterolemia and are pleased the FDA has indicated that we have adequate data to proceed into Phase 3 clinical trials," stated Sheldon Koenig, President and CEO of Esperion. "This alignment supports our commitment to broaden the reach of our bempedoic acid products as part of our lifecycle management plan, providing the opportunity to extend our patent protection for an additional six months for these important therapies."
Phase 3 Trial Design
The Phase 3 program consists of two parallel studies: CLEAR Path 2 for children with heterozygous familial hypercholesterolemia (HeFH) and CLEAR Path 3 for children with HoFH. Both are randomized, double-blind, placebo-controlled, multicenter studies designed to evaluate the efficacy and safety of bempedoic acid with and without concurrent ezetimibe.
The trials will enroll pediatric patients with LDL-C levels ≥130 mg/dL (3.4 mmol/L) despite treatment with protocol-defined optimum doses of statins. Each study follows a 52-week design where participants will be randomized 2:1 to treatment or control for 24 weeks, followed by a 28-week open-label extension period.
Understanding Familial Hypercholesterolemia
Familial hypercholesterolemia is a genetic condition that causes elevated cholesterol levels from birth and, if untreated, leads to early, aggressive atherosclerotic cardiovascular disease. The condition exists in two forms:
HeFH is the more common form, occurring in approximately 1 in 250 births. It results from inheriting a gene that causes FH from one parent. Without treatment, cardiovascular disease typically develops during middle adulthood.
HoFH is significantly rarer, occurring in approximately 1 in 300,000 births. It results from inheriting FH genes from both parents, leading to substantially higher cholesterol levels that are often more difficult to treat. Without intervention, cardiovascular disease can begin as early as childhood.
Both forms of FH are characterized by disrupted processing of LDL-C due to genetic mutations, resulting in dangerously high LDL-C levels. Despite their serious health implications, both HeFH and HoFH remain underdiagnosed and undertreated.
Commercial and Patent Implications
The advancement to Phase 3 trials carries significant strategic importance for Esperion beyond the clinical benefits for pediatric patients. Successful completion of pediatric studies will secure an additional six-month patent extension for bempedoic acid, extending protection through June 2031.
Bempedoic acid is currently approved for adult patients with elevated LDL-C who are at risk for cardiovascular disease. The medication's efficacy and safety in adults were demonstrated in the CLEAR Cardiovascular Outcomes Trial, which enrolled nearly 14,000 patients.
The pediatric development program represents an important expansion of Esperion's portfolio and addresses a significant unmet need in children with genetic cholesterol disorders. Early intervention in these patients is critical, as controlling LDL cholesterol from a young age can significantly reduce the risk of premature cardiovascular disease.
Future Outlook
Esperion continues to build on its success with bempedoic acid while advancing its next-generation program focused on developing ATP citrate lyase inhibitors (ACLYi). The company reports that new insights into the structure and function of ACLYi have enabled rational drug design and the opportunity to develop highly potent and specific inhibitors with allosteric mechanisms.
As Esperion evolves into a global biopharmaceutical company, its strategy encompasses commercial execution, international partnerships, and advancement of its pre-clinical pipeline. The pediatric development program for bempedoic acid represents an important step in this broader strategy, potentially bringing a new treatment option to children with a serious genetic disorder while extending the commercial lifecycle of the company's lead product.
