ACC 2022 – Silence takes on Novartis and Amgen

A couple of years ago the small interfering RNA specialist Silence Therapeutics refocused efforts on SLN360, a project designed to decrease lipoprotein(a) in cardiovascular disease. Now the company has promising, albeit early, data that could see it compete against the likes of Novartis and Amgen. The phase 1 Apollo study, presented at ACC yesterday, found that a single 300mg or 600mg dose of SLN360 decreased lipoprotein(a) levels by 70% and 81% respectively at five months. With the usual caveats about cross-trial comparisons, this looks about in line with regular dosing of the field’s leader, Novartis’s pelacarsen. In phase 2 the highest doses of the latter, 60mg monthly or 20mg weekly, reduced lipoprotein(a) by 72% and 80% respectively at six months. Novartis is testing an 80mg monthly dose in its pivotal Lp(a)Horizon trial. One patient in Apollo, receiving a 30mg dose of SLN360, had liver enzyme elevations, but the most common adverse events were injection site reactions. Phase 2 is due to start later this year. If Silence can keep up this performance it could have a contender on its hands, although it will need a partner to go up against Novartis and Amgen’s marketing muscle.

Projects in clinical development targeting apolipoprotein A
Project Company Description Trial details
Pelacarsen Novartis (licensed from Ionis) ApoA antisense  Ph3 Lp(a)Horizon in pts with CVD & elevated Lp(a) completes May 2025
Olpasiran (AMG 890) Amgen (licensed from Arrowhead) ApoA siRNA Ph2 in pts with CVD & elevated Lp(a); topline data due H1 2022
SLN360 Silence Therapeutics ApoA siRNA Ph1 Apollo in pts with elevated Lp(a); single-dose portion in those without known ASCVD, multi-dose portion in those with ASCVD; ph2 to start H2 2022
ASCVD=Atherosclerotic cardiovascular disease. Source: Evaluate Pharma &

Lp(a) lowering with a single dose of SLN360

Source: Dr Steven Nissen and ACC.

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