Add-on recaticimab cuts bad cholesterol in non-FH, mixed hyperlipidaemia patients

In the phase III REMAIN-2 trial, add-on recaticimab – a novel, long-acting anti-PCSK9 monoclonal antibody (mAb) – led to reductions in bad cholesterol and other lipids in patients with non-familial hypercholesterolaemia (non-FH) and mixed hyperlipidaemia inadequately controlled on background statin therapy.

At week 24, there were greater LDL-C* reductions with recaticimab vs placebo, with similar efficacy across the different dosing regimens. The least squares mean (LSM) changes from baseline for the 150-mg Q4W, 300-mg Q8W, and 450-mg Q12W doses were -62.2, -59.7, and -53.2 percent, respectively. All comparisons against placebo yielded p-values of <0.0001.

These reductions were maintained through week 48 (-60.1, -64.0, and -48.4 percent for the respective 150-, 300-, and 450-mg doses; p<0.0001 for all).

Moreover, the LDL-C reductions across all recaticimab doses occurred regardless of age, BMI, baseline LDL-C, ASCVD** history, or type 2 diabetes. [AHA 2023, session LBS.06]

LDL-C control at 24 weeks was also better with recaticimab than placebo. In the overall cohort, 86–94 percent of participants on recaticimab achieved the LDL-C goal, as opposed to 14–16 percent in the placebo arm. This effect was similarly seen in participants with or without ASCVD.

Other lipid parameters, safety

Recaticimab also trumped placebo in terms of reductions in other key lipid parameters such as non-HDL-C*, Apolipoprotein B (ApoB), and lipoprotein(a). The LSM changes from baseline in non-HDL-C ranged between -47.6 and -56.6 percent across all three recaticimab doses (p<0.0001 for all). For ApoB, the reductions were between -44.4 and -53.3 percent, while for lipoprotein(a), the reductions fell between -28.1 and -36.1 percent (p<0.0001 for all).

“Recaticimab reduced these key lipid parameters by a magnitude similar to other PCSK9 inhibitors, providing further evidence of profound benefits with the treatment despite less frequent dosing,” said lead author Dr Xin Du from the Beijing Anzhen Hospital and Capital Medical University, Beijing, China, at AHA 2023.

Recaticimab was well tolerated over 48 weeks, with a similar overall incidence of treatment-related adverse events (TRAEs) between recaticimab and placebo. The most common TRAEs tied to recaticimab were elevations in alanine transaminase (4.6 percent) and blood creatine phosphokinase levels (4.4 percent).

Frequent dosing limits compliance

Despite the reported efficacy of approved anti-PCSK9 mAbs, the frequent dosing regimens limit compliance in the real-world setting. [Int J Cardiol 2018;260:196-203; N Engl J Med 2014;370:1809-1819; N Engl J Med 2015;372:1489-1499]

“[Up to] 40 percent of people discontinue their current PCSK9 therapies given every 2–4 weeks, during or after 6 months of starting treatment,” Du said. Given the more flexible dosing of recaticimab, more individuals with elevated LDL-C levels may be encouraged to stick to their regimens, Du added.

The team randomized 692 patients (mean age 55.8 years, 64 percent men) 2:2:2:1:1:1 to recaticimab 150 mg Q4W, 300 mg Q8W, 450 mg Q12W, or matching placebo for 48 weeks. More than 85 percent of patients were on moderate-intensity background statins (atorvastatin or rosuvastatin). About 10 percent were on concomitant ezetimibe. Mean LDL-C at baseline was 2.8 mmol/L.

Infrequent dosing offers flexibility

“[REMAIN-2 showed that] add-on recaticimab [is] an effective therapeutic option with an infrequent dosing interval in patients with non-FH and mixed hyperlipidaemia inadequately controlled on stable statin therapy,” Du said.

“Since all doses and frequencies had similar efficacy and safety, this may someday provide patients and physicians with more flexible options,” Du added. “Further studies will be conducted to explore the possible benefits of recaticimab in reducing cardiovascular risk.”

REMAIN-3 is underway to ascertain the potential of recaticimab to deliver a lipid-lowering benefit in individuals with heterozygous familial hypercholesterolaemia.