Evinacumab was found to be safe and well-tolerated and was associated with a sustained reduction in the levels of low-density lipoprotein cholesterol in patients diagnosed with refractory hypercholesterolemia.
Individuals diagnosed with refractory hypercholesterolemia do not achieve the target levels of low-density lipoprotein cholesterol (LDL-C) despite lipid-lowering treatment at maximally tolerated dosages. These refractory hypercholesterolemia patients are at greater risk for atherosclerotic cardiovascular disease.
In a recent double-blind randomized controlled trial, researchers assessed the safety and efficacy of long-term treatment with evinacumab in refractory hypercholesterolemia patients. The findings are published in the Journal of the American Medical Association.
Baseline Characteristics
The study included a total of 96 patients with a mean age of 54.4 ± 11.3 years. The study population comprised 54.2% females. Approximately 91.7% of the participants completed the 48-week open-label treatment period (OLTP). Of the study population, 82.3% were diagnosed with heterozygous familial hypercholesterolemia (HeFH).
Evinacumab and Low-Density Lipoprotein Cholesterol Levels
At the end of OLTP, the administration of 15 mg/kg of evinacumab led to a reduction in LDL-C levels from the baseline, with a mean percentage change in the LDL-C levels of 45.5 ± 28.7% in the overall pool of participants. The mean absolute reduction in the levels of LDL-C at week 72 compared to the baseline was 72.2 ± 55.4 mg/dL in the overall cohort. The percentage of patients who achieved LDL-C levels < 55 mg/dL, < 70 mg/dL, and < 100 mg/dL at the end of OLTP was 31.3%, 52.5%, and 82.5%, respectively.
Safety Profile of Evinacumab in Refractory Hypercholesterolemia Patients
Of the total participants, 81.3% reported a minimum of one treatment-emergent adverse event (TEAE) over the OLTP. The most common TEAE in patients administered 15 mg/kg evinacumab was nasopharyngitis, experienced by 12.5% of the patients. Four patients from the study cohort reported at least one TEAE attributed to the treatment. These adverse events included mild influenza-like illness, moderate increase in LDL-C levels, frequent bowel movements, and malaise. Serious TEAEs were reported in 9.4% of the patients. These included carotid artery stenosis, dyspnea, atrial fibrillation, palpitations, chest pain, infection with coronavirus, impaired gastrointestinal motility, gallbladder polyp, pulmonary embolism, transitional cell carcinoma, and joint effusion.
Source:
Rosenson, R. S., Burgess, L., Ebenbichler, C., Baum, S., Stroes, E. S., Ali, S., Khilla, N., McGinniss, J., Gaudet, D., & Pordy, R. (2023). Longer-Term efficacy and safety of Evinacumab in patients with refractory hypercholesterolemia. JAMA Cardiology, 8(11), 1070. https://doi.org/10.1001/jamacardio.2023.2921
