Recaticimab delivers promising outcomes in non-FH, mixed hyperlipidaemia

Monotherapy with recaticimab can significantly lower low-density lipoprotein cholesterol (LDL-C) levels in patients with nonfamilial hypercholesterolemia (non-FH) and mixed hyperlipidaemia, according to data from the phase III REMAIN-1 study presented at ESC 2023.

The drug affords LDL-C-lowering benefit even with an infrequent dosing interval, reported principal investigator Prof Junbo Ge of Zhongshan Hospital, Fudan University in Shanghai, China.

LDL-C dropped significantly from baseline with recaticimab 150 mg every 4 weeks (Q4W) and 450 mg every 12 weeks (Q12W) at week 12, as well as with 300 mg every 8 weeks (Q8W) at week 16 than with placebo. The corresponding percentage change in LDL-C was –49.6 percent (–54.9 percent to –44.2 percent; p<0.0001) for 150 mg Q4W, –45.0 percent (–49.0 percent to –41.0 percent; p<0.0001) for 450 mg Q12W, and –52.8 percent (–57.2 percent to –48.3 percent; p<0.0001) for 300 mg Q8W. [Ge J, et al, ESC Congress 2023]

Secondary outcomes

“Recaticimab was also superior to placebo in [terms of] achieving the LDL-lowering target and reducing other key lipid parameters,” Ge noted.

The proportion of patients who achieved LDL-C levels <2.6 mmol/L was 88.2 percent with 150 mg Q4W vs 7.5 percent with placebo and 86.8 percent with 450 mg Q12W vs 3.9 percent with placebo at week 12, and then 91.0 percent with 300 mg Q8W vs 8.2 percent with placebo at week 16.

In addition, compared with those on placebo, patients across all three recaticimab dose groups showed significantly greater reductions in nonhigh-density lipoprotein cholesterol (difference, from –43.4 percent to –47.3 percent; p<0.0001 for all), apolipoprotein B (difference, from –40.3 percent to –43.6 percent; p<0.0001 for all), and lipoprotein (a) (difference, from –18.3 percent to –32.4 percent; p<0.0001 for all).

In all dose groups, the effects of recaticimab on LDL-C percentage change were consistent across subgroups defined by age, BMI, and baseline LDL-C, according to Ge.

Extended treatment period

Additional data from the extended period where patients on recaticimab continued with their treatment and those on placebo switched to recaticimab confirmed that the drug was efficacious. Through 24 weeks of treatment, recaticimab continued to lower LDL-C, with a reduction of 47.3–53.1 percent and with 84.5–92.8 percent of patients achieving the target.

Meanwhile, patients who switched from placebo to recaticimab showed similar LDL-C reduction at week 24 compared with those initially assigned to receive recaticimab, Ge noted.

Safety profile

In terms of safety, the frequency of treatment-related adverse events (TRAEs) across the recaticimab dose groups was low and comparable to the placebo group (week 12-16: 14.1 percent overall vs 11.1 percent; week 24: 25.9 percent). Injection site reaction was the most common TRAE, followed by upper respiratory tract infection and hyperuricaemia.

Recaticimab is a novel humanized IgG1 monoclonal antibody that selectively targets PCSK9. Ge explained that the drug possesses long-acting effects by inhibiting FcRn-mediated antibody catabolism, thereby extending the half-life.

Taken together, these findings suggest that “recaticimab as monotherapy represents a promising lipid-lowering treatment option in patients with non-FH and mixed hyperlipidaemia,” he said.

Ge saw it to be encouraging, given the challenges that come with treating dyslipidaemia, including poor statin therapy compliance due to frequent administration or intolerance, requirement of anti-PCSK9 antibodies, and low rates of LDL-C target achievement, especially in China. [Int J Cardiol 2018;260:196-203]

Antidrug antibodies

At the end of the presentation, several experts raised concerns regarding the long-term use of fully human monoclonal antibodies and a potential increase in antidrug antibodies (ADA). They asked whether this would be a problem considering that REMAIN-1 only presented data covering 24 weeks of treatment as opposed to other studies of monoclonal antibodies with 1 year of data.

In response, Ge pointed out that the purity of recaticimab was quite high at more than 95 percent, adding that the drug would not likely cause problems with respect to ADAs over long periods of use, he said. But as to whether the effect of the drug would wane over that period, Ge could not tell.

REMAIN-1 included adult non-FH and mixed hyperlipidaemia with a fasting LDL-C level of ≥2.6 to <4.9 mmol/L, a fasting triglyceride level of ≥5.6 mmol/L, and a 10-year atherosclerotic cardiovascular disease (ASCVD) risk score of <10 percent. A total of 157, 156, and 155 patients comprised the 150 mg Q4W, 300 mg Q8W, and 450 mg Q12W dose groups, respectively, and 78, 79, and 78 patients comprised the comparator placebo groups.