medwireNews: Recaticimab monotherapy significantly lowers low-density lipoprotein (LDL) cholesterol even at infrequent dosing intervals in patients with nonfamilial hypercholesterolemia and mixed hyperlipemia, shows the REMAIN-1 study published in the Journal of the American College of Cardiology.
All patients had residual dyslipidemia at the study start, despite existing medication, and were at low-to-moderate risk of atherosclerotic cardiovascular disease (ASCVD), with a 10-year risk of less than 10%.
LDL cholesterol was a mean of 3.7 mmol/L at baseline and recaticimab, a long-acting proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, significantly reduced the level by 50.4% at 12 weeks in participants given 150 mg every 4 weeks, by 50.5% at 16 weeks in those given 300 mg every 8 weeks, and by 45.6% at 12 weeks in those given 450 mg every 12 weeks. By comparison, LDL cholesterol levels in the placebo groups fell by 0.8%, increased by 2.3%, and decreased by 0.6%, respectively.
“The capacity to […] reduce LDL-[cholesterol] levels via PCSK9 inhibition presents an opportunity for early intervention,” comment study investigators JunBo Ge (Zhongshan Hospital, Shanghai, China) and colleagues. They note that the efficacy and safety of recaticimab was evident even at infrequent dosing intervals of up to 12 weeks, providing the option of flexible administration strategies.
The team also comments that “[t]his extended dosing interval could substantially improve the convenience and adherence to medication for patients, thereby supporting the sustainable management of disease over time.”
Editorialists Michael Shapiro (Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA) and colleagues highlight several limitations in REMAIN-1, including the exclusively Chinese study population which precludes generalizability of the findings, and the lack of cardiovascular outcomes data, but they say that “if these challenges are addressed, recaticimab could become a valuable addition to the lipid-lowering armamentarium.”
Ge et al assessed the three recaticimab dosing strategies in 703 Han Chinese patients (46.2% to 58.0% men, median age 42 to 48 years) who were required to discontinue any other lipid-lowering therapies and maintain a healthy lifestyle including a lipid-lowering diet throughout the study.
The increased reduction in LDL-cholesterol achieved with recaticimab (n=468) relative to placebo (n=235) at the end of the treatment period was a significant 49.6 percentage points at week 12 with recaticimab 150 mg every 4 weeks, 52.8 percentage points at week 16 with 300 mg every 8 weeks, and 45.0 percentage points at week 12 with 450 mg every 12 weeks.
This equated to absolute reductions relative to placebo of 1.8 mmol/L, 1.9 mmol/L, and 1.6 mmol/L, respectively.
The researchers also found that significantly more patients on recaticimab achieved a reduction in their LDL-cholesterol to a target of below 2.6 mmol/L (86.9 to 91.0% vs 3.9 to 8.2%), and several other atherogenic lipids were also lower in patients who received recaticimab rather than placebo, including non-high-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a), but not triglyceride.
Within the treatment period, treatment-related adverse events (TRAEs) were reported in 14.1% of recaticimab-treated patients overall and 11.1% of placebo-treated patients, with the most common being injection-site reactions (3.0 vs 1.7%, respectively) and upper respiratory tract infections (1.7 vs 2.1%).
Around 5.4% of recaticimab-treated patients developed antidrug antibodies (ADA) and neutralizing antibodies were detected in 1.2%; however, the investigators say: “There was no difference in the effect of recaticimab on lowering LDL-[cholesterol] between ADA-positive and -negative patients, as well as the occurrence of TRAEs.”
The immunogenicity of PCSK9 inhibitors is a key focus, notes Shapiro and fellow editorialists, who add that the findings for recaticimab suggest “the observed immunogenicity does not compromise the therapeutic benefits or safety profile of the drug.”
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