Shares of Silence Therapeutics SLN plunged 36.8% on Tuesday despite reporting positive end-of-treatment data from a mid-stage study of lead candidate, zerlasiran, to treat atherosclerotic cardiovascular disease (ASCVD) patients with high lipoprotein(a) or Lp(a), a key genetic risk factor for cardiovascular disease. The stock price drop is likely due to investors’ skepticism regarding the effectiveness of the candidate compared to other treatments being developed for the same indication.

The results from the phase II ALPACAR-360 study of zerlasiran for the ASCVD indication were presented at a medical conference in Chicago, IL, and simultaneously published in the Journal of the American Medical Association.

Per the data readout, zerlasiran, administered at doses of 300 mg every 16 or 24 weeks or 450 mg every 24 weeks, achieved more than 80% mean time-averaged placebo-adjusted reductions in Lp(a) levels over 36 weeks, with maximum reductions surpassing 90%. At the final follow-up, 60 weeks after the initial dose, Lp(a) reductions were sustained, and the treatment remained safe with infrequent dosing.

However, it was also observed that Lp(a) reduction levels with zerlasiran in the ALPACAR-360 study declined between the 16 weeks and 24 weeks 300mg doses, signifying diminishing efficacy. This has raised questions regarding the competitive profile of the drug compared to a therapeutic candidate being developed by Amgen AMGN for the same indication.

Year to date, shares of Silence Therapeutics have plunged 59.9% compared with the industry’s 6.9% decline.

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SLN Competes With Amgen in the ASCVD Market

Amgen is also currently evaluating a potentially best-in-class siRNA molecule, olpasiran, for reducing Lp(a) synthesis in ASCVD patients in a late-stage cardiovascular outcomes study. Last year, Amgen reported final data from the phase II OCEAN(a)-DOSE study of the candidate for the ASCVD indication.

During the off-treatment extension period, olpasiran demonstrated a lasting impact on Lp(a) levels, maintaining a 40-50% placebo-adjusted reduction nearly a year after the last dose. In 2022, Amgen reported that doses of olpasiran ≥75 mg, administered every 12 weeks, reduced Lp(a) by more than 95% at week 36. No new safety concerns emerged during the off-treatment phase.

Silence Therapeutics believes that at least 20% of the global population is affected by elevated Lp(a) levels, which is a major cause of morbidity and mortality in ASCVD patients. Based on the mid-stage study results, Silence Therapeutics is currently analyzing available information to select the best dose and dosing interval for future late-stage studies of zerlasiran to treat ASCVD patients with high Lp(a).

Apart from zerlasiran, Silence Therapeutics has another clinical-stage candidate, divesiran, in its pipeline which is being evaluated in a phase I/II study for polycythemia vera.

Silence Therapeutics PLC Sponsored ADR Price and Consensus

Silence Therapeutics PLC Sponsored ADR price-consensus-chart | Silence Therapeutics PLC Sponsored ADR Quote

SLN’s Zacks Rank and Stocks to Consider

Silence Therapeutics currently carries a Zacks Rank #3 (Hold).

Some better-ranked pharma stocks are Allogene Therapeutics ALLO and Pfizer PFE, each carrying a Zacks Rank #2 (Buy) at present. You can see the complete list of today’s Zacks #1 Rank (Strong Buy) stocks here.

Over the past 60 days, Allogene Therapeutics’ estimates for loss per share have narrowed from $1.40 to $1.35 for 2024, and that for 2025 has narrowed from $1.46 to $1.34. ALLO shares have lost 34% year to date.

Allogene Therapeutics’ earnings beat estimates in three of the trailing four quarters and matched once, delivering an average surprise of 9.42%.

Over the past 60 days, Pfizer’s earnings estimates have risen from $2.62 to $2.91 per share for 2024, while that for 2025 has increased from $2.85 to $2.92. PFE shares have lost 12.8% year to date.

Pfizer’s earnings beat estimates in each of the trailing four quarters, delivering an average surprise of 74.50%.

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