Silence Therapeutics' Zerlasiran Has Competitive Concerns: Analyst

On Monday, Silence Therapeutics plc SLN presented end-of-treatment data from its Phase 2 ALPACAR-360 study of zerlasiran in atherosclerotic cardiovascular disease (ASCVD) patients with high lipoprotein(a) [Lp(a)] levels (≥125 nmol/L).

These data were presented at the American Heart Association (AHA) Scientific Sessions.

Results showed that zerlasiran (300 mg every 16 weeks, 300 mg every 24 weeks or 450 mg every 24 weeks) produced greater than 80% mean time-averaged placebo-adjusted reductions from baseline in Lp(a) concentrations over 36 weeks.

This is the first study to report time-averaged Lp(a) analyses, which more accurately evaluate the effects of treatment over time, including intervals between doses.

Maximum Lp(a) reductions exceeded 90%. At the final visit, 60 weeks following initial drug administration, reductions in Lp(a) persisted, and no safety concerns emerged with infrequent dosing.

William Blair notes that while Silence's data shows the drug effectively lowers Lp(a) levels, the Q24W dosing schedule may not be competitive. This is due to a decline in Lp(a) reduction between doses.

This dosing schedule could be an option for maintenance after stable Lp(a) reductions are reached. However, the analyst expects more frequent dosing, possibly every three months, to be needed. This may reduce zerlasiran's competitive edge compared to Amgen Inc.'s AMGN olpasiran.

The analyst writes, "Silence continues to execute on both the zerlasiran and divesiran lead clinical programs. While data for zerlasiran presented at AHA show that zerlasiran is an efficacious Lp(a) lowering agent over 48 weeks with Q24W dosing, we are incrementally negative on zerlasiran's competitive profile given the waning of Lp(a) lowering between the infrequent doses, which has not been demonstrated with olpasiran at a once-quarterly dosing frequency."

Price Action: SLN stock is down 33.80% at $7.20 at the last check on Tuesday.

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