Lipoprotein(a) slashed by 98% in APOLLO trial

Results from the first-in-human, phase 1 APOLLO study showed that the investigational short interfering RNA (siRNA) therapy called SLN360 was safe and lowered lipoprotein(a) (Lp[a]) by up to 98%.

Prof. Steven Nissen (Cleveland Clinic, OH, USA) presented the findings of the phase 1 APOLLO study (NCT04606602), which was simultaneously published in JAMA [1,2]. The primary outcome measures of APOLLO were the safety, tolerability, pharmacokinetics, and pharmacodynamics of SLN360 after single ascending subcutaneous doses in 32 participants with elevated Lp(a) levels and no known cardiovascular disease. The main secondary outcome was a change in Lp(a) plasma concentration after a follow-up of no more than 150 days.

Prof. Nissen explained that study participants (mean age 50 years; 53% women) were randomised into several cohorts to receive either placebo (n=8) or subcutaneous single doses of SLN360 siRNA at 30 mg (n=6), 100 mg (n=6), 300 mg (n=6), or 600 mg (n=6). All participants completed the trial.

The primary endpoint was met, and although 1 participant had 2 serious adverse events that required hospitalisation, neither event was attributed to the study drug. All other participants had no or minor adverse events to SLN360, which the independent committee determined to be well tolerated.

With regard to the lipid-lowering efficacy, reduction in baseline Lp(a) plasma levels showed a dose response to SLN360 concentrations, corresponding to a median reduction of 46%, 86%, 96%, and 98% at about 45 to 60 days with 30 mg, 100 mg, 300 mg, and 600 mg doses, respectively.

Collectively, the data from this early phase siRNA treatment for lipid reduction appears to be safe and effective but will require additional clinical testing to determine the effect on cardiovascular outcomes.

1. 
   
   1. Nissen S, et al. Magnitude And Duration Of Effects Of A Short-interfering RNA Targeting Lipoprotein(a): A Placebo-controlled Double-blind Dose-ranging Trial. Abstract 405–14, ACC 2022, 2–4 April, Washington DC, USA.
   2. Nissen SE, et al. JAMA. 2022;327(17):1679–87.

 

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Posted on 15 June 202223 April 2024