Evolocumab in patients with homozygous familial hypercholesterolemia in India

Background: Evolocumab is a fully human monoclonal antibody inhibitor of proprotein convertase subtilisin/kexin type 9 approved in India for treatment of homozygous familial hypercholesterolemia (HoFH) in patients aged >= 12 years. Objective: RAMAN (NCT03403374) was a single-country, open-label, phase 4 study evaluating the safety and tolerability of evolocumab in patients with HoFH in India. Methods: Patients >= 12 to <= 80 years of age on stable lipid-lowering therapy with fasting low-density lipoprotein cholesterol (LDL-C) >3.4 mmol/L (>130 mg/dL) received evolocumab 420 mg subcutaneously monthly (every 2 weeks if on apheresis). The primary endpoint was patient incidence of treatment-emergent adverse events. Secondary endpoints included percent changes at week 12 in LDL-C and other lipids. Results: Of 30 enrolled patients, 13 were <18 years of age. Mean +/- SD baseline levels of LDL-C, apolipoprotein B, and lipoprotein(a) were 12.3 +/- 3.5 mmol/L (473.5 +/- 135.2 mg/dL), 2.8 +/- 0.7 g/L (275.3 +/- 69.1 mg/dL), and 201.3 +/- 177.6 nmol/L, respectively. Ten patients (33%) reported treatment-emergent adverse events, with 2 (7%) serious adverse events and none leading to discontinuation; no deaths occurred during evolocumab treatment. At week 12, mean (SE) percent changes from baseline in LDL-C, apolipoprotein B, and lipoprotein(a) were -6.4% (4.2), -6.0% (3.7), and -0.2% (4.9), respectively. Reductions in LDL-C among individual patients were variable and greatest in patients >= 18 years of age and with baseline LDL-C <13 mmol/L (<500 mg/dL). Conclusions: Evolocumab was safe and well tolerated in patients with HoFH in India with smaller reductions in LDL-C and other lipids than those observed in previous studies with HoFH and different populations. (C) 2021 National Lipid Association. Published by Elsevier Inc.