Silence Therapeutics has reported positive topline data from a Phase I trial of its SLN360 in adults with high lipoprotein(a) (Lp(a)).

An investigational small interfering ribonucleic acid (siRNA) SLN360 can potentially reduce the production of Lp(a) by acting on messenger RNA transcribed from the LPA gene.

The trial analysed the safety, tolerability, pharmacodynamics and pharmacokinetics (PK) of escalating doses of SLN360 in 32 adult subjects.

Trial subjects had plasma concentrations of Lp(a) ≥150nmol/L without any identified cardiovascular disease. 

Participants were randomised to receive either 30mg, 100mg, ≤ 300mg or ≤ 600mg single subcutaneous dose of SLN360 or placebo and were monitored for up to 150 days.

Evaluating treatment-emergent adverse events was the primary safety objective of the trial. 

Findings showed that no clinically relevant safety concerns were identified. 

Low-grade adverse events were noted at the injection site, of which more prominent were reported at the high dose. 

Furthermore, SLN360’s systemic exposures (PK) increased dose proportionally.

Percent change from baseline in Lp(a) was the key efficacy analysis of the trial. 

SLN360 showed to lower Lp(a) from 46% to nearly 98% in a dose-dependent manner while up to an 81% reduction continued at 150 days. 

To analyse the action period further, the follow-up period of the trial was expanded from 150 days to 365 days.

The company expects results from this extended period in the third quarter of this year.

Silence Therapeutics R&D head, executive vice-president and chief medical officer Giles Campion said: “These first-in-human data for SLN360, which align with our pre-clinical findings, reinforce our confidence in its potential to substantially lower Lp(a) levels with long-lasting action and address a major unmet need in cardiovascular disease. 

“More broadly, siRNA is proving to be a powerful modality for treating genetic conditions, both common and rare, by precisely engaging targets that have previously been considered ‘undruggable’.”