Silence's siRNA therapy proves long-term efficacy in cardiovascular study

Silence Therapeutics announced promising long-term results from the Phase II ALPACAR-360 study of its gene silencing therapy, zerlasiran (SLN360). The drug showed significant and sustained reductions in lipoprotein(a) [Lp(a)] levels over 48 weeks in patients at high risk of atherosclerotic cardiovascular disease events. This study, which included 178 participants with baseline Lp(a) levels of 125 nmol/L or higher, found that administering zerlasiran doses of 300mg subcutaneously every 16 or 24 weeks, or 450mg every 24 weeks, led to a median maximum reduction in Lp(a) levels of approximately 90% or more during the treatment period.

Encouraged by these findings, Steven Romano, the Chief of R&D at Silence Therapeutics, indicated that the results support a less frequent dosing regimen, potentially extending to at least quarterly doses of 300mg. The company plans to advance zerlasiran into Phase III trials. The 48-week data build on earlier positive results at the 36-week mark, where the primary endpoint of the study was met with significant reductions in Lp(a) levels compared to a placebo group. Full results from this 60-week study will be presented at a future scientific meeting.

These developments are part of a series of positive milestones for Silence Therapeutics. Earlier this year, AstraZeneca, a partner in Silence’s 2020 siRNA collaboration, initiated a Phase I trial for the first product candidate from this partnership, which triggered a $10-million milestone payment to Silence. The agreement with AstraZeneca includes potential milestone payments up to $400 million for each of five targets, with the possibility of extending the deal to cover an additional five targets.

In addition to these clinical advancements, Silence Therapeutics bolstered its financial standing in February with a $120-million private placement. This funding round was oversubscribed, indicating strong interest from both new and existing institutional investors. The funds are allocated to support the company’s ongoing clinical programs, including the advancement of zerlasiran. Moreover, the financial injection will assist in moving Silence’s siRNA therapeutic divesiran (SLN124) into Phase II for polycythemia vera, as well as further development of its mRNAi GOLD platform.

Silence Therapeutics’ progress with zerlasiran, alongside its strengthened financial position, highlights the company’s strategic forward momentum in the field of gene silencing therapies. The promising data from the ALPACAR-360 study not only underscore the potential of zerlasiran in reducing Lp(a) levels but also pave the way for future research and clinical applications, marking a significant step in addressing atherosclerotic cardiovascular disease.