Breakthrough in Rare Cholesterol Treatment: FDA Greenlit Novel Evkeeza Therapy Transforms Care for Ultra-Rare Genetic Condition

Regeneron Pharmaceuticals has achieved a significant milestone with the FDA’s approval of Evkeeza (evinacumab-dgnb), marking the first-ever therapeutic intervention targeting ANGPTL3 for patients battling homozygous familial hypercholesterolemia (HoFH)—an exceptionally uncommon inherited disorder affecting only around 1,300 Americans. This approval fundamentally reshapes treatment possibilities for individuals inheriting two copies of FH-causing genes, resulting in dangerously elevated LDL-C levels exceeding 400 mg/dL.

Understanding the Clinical Challenge

HoFH represents one of the most severe manifestations of familial hypercholesterolemia, condemning patients to premature cardiovascular disease and cardiac events as early as adolescence. The baseline LDL-C levels in affected patients average 255 mg/dL or higher, placing them in acute danger despite conventional lipid-lowering interventions. Traditional therapeutic approaches have proven inadequate for the majority of HoFH patients, leaving clinicians with limited options and families facing grim prognoses.

The Clinical Evidence Supporting Approval

The FDA’s decision rests on compelling data from the Phase 3 ELIPSE HoFH trial, which demonstrated evkeeza’s remarkable efficacy. In this randomized study involving 65 patients, those receiving intravenous Evkeeza injections every four weeks (43 participants) plus standard lipid-lowering medications achieved a 49% reduction in LDL-C levels by week 24. By comparison, the control group receiving only standard therapies showed a 2% increase in LDL-C levels, underscoring the treatment’s distinctive value.

Mechanism of Action: A Novel Approach

Evkeeza operates through a unique mechanism—it binds to and inhibits ANGPTL3, a protein critical to lipid metabolism regulation. This innovative approach proves particularly transformative because it effectively lowers LDL-C across all HoFH variants, including patients with minimal LDL receptor activity who previously had virtually no effective options.

Expert Perspectives and Clinical Impact

Daniel J. Rader, M.D., Professor and Chair of Genetics at the University of Pennsylvania and a leading HoFH researcher involved in clinical trials, characterizes evkeeza as “potentially transformational,” emphasizing that existing therapies fall short for most patients. The medication represents a meaningful advancement in controlling cholesterol levels across the full spectrum of HoFH presentations.

Katherine A. Wilemon, Founder and CEO of the FH Foundation, describes the approval as a watershed moment, acknowledging that HoFH patients have long faced devastatingly high cholesterol levels with limited hope. Evkeeza now offers an important new therapeutic pathway for this vulnerable population.

Regeneron’s Achievement

George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron, highlights that this approval exemplifies the company’s development philosophy—leveraging genetic insights and cutting-edge technology to address unmet medical needs. The successful development of evkeeza underscores Regeneron’s commitment to delivering solutions for patient populations with minimal existing treatment options.