Silence Therapeutics Announces Positive Topline 48-Week Data from Phase 2 Study of Zerlasiran in Patients with Elevated Lipoprotein(a)

Rhea-AI Summary

Silence Therapeutics (Nasdaq: SLN) announced positive topline 48-week data from its ALPACAR-360 Phase 2 study of zerlasiran, a siRNA targeting elevated lipoprotein(a), a key genetic risk factor for cardiovascular disease. The study included 178 subjects with baseline Lp(a) levels of 125 nmol/L or higher, administered doses of 300 mg and 450 mg subcutaneously. Results showed a 90% or greater median reduction in Lp(a) from baseline compared to placebo. Zerlasiran was well tolerated with no serious safety concerns. The company plans to advance to Phase 3 trials.

Positive

• Phase 2 study of zerlasiran showed a 90% or greater reduction in Lp(a) levels.
• Well-tolerated with no serious safety concerns reported.
• Supports advancing zerlasiran to Phase 3 trials.

Negative

• None.

Insights

Medical Research Analyst

Silence Therapeutics' recent data from the phase 2 study of zerlasiran offers noteworthy news for the biotechnology and healthcare sectors. The data indicates a 90% reduction in lipoprotein(a) (Lp(a)) levels, a significant genetic risk factor for cardiovascular disease (CVD). This is promising because elevated Lp(a) is implicated in increased risk for atherosclerotic cardiovascular disease (ASCVD).

From a medical standpoint, a reduction of this magnitude is remarkable. Drugs aiming to reduce Lp(a) typically face substantial challenges in achieving sustained efficacy. The fact that zerlasiran not only achieved but maintained this reduction to week 48 is indicative of its potential as a game-changer in CVD management.

Furthermore, zerlasiran’s favorable safety profile, with no serious safety concerns reported, is important for regulatory approval and patient compliance. The promise of infrequent dosing—potentially every 16 to 24 weeks—enhances its attractiveness, reducing the treatment burden on patients.

In conclusion, these results bolster the case for advancing zerlasiran to phase 3 trials. The continuation of the study to week 60 will be pivotal in confirming these findings.

Financial Analyst

The positive topline data from Silence Therapeutics' phase 2 study of zerlasiran has significant financial implications. The demonstrated efficacy and favorable safety profile greatly enhance the drug's value proposition, potentially positioning it as a leading treatment for patients with elevated lipoprotein(a) levels—a market with significant unmet needs.

For investors, the prospect of advancing to phase 3 trials suggests a clear pathway to potential regulatory approval and commercialization. This could lead to substantial revenue streams given the high prevalence of elevated Lp(a) levels globally, affecting 20% of the population.

In the short term, expect a positive market reaction as confidence in the drug's efficacy and safety grows. Long-term, the success of phase 3 trials could substantially increase the company’s market valuation and attract strategic partnerships or acquisition offers.

However, the financial landscape is not without risks. The costs associated with phase 3 trials are significant and any unforeseen safety issues or lack of efficacy in the extended study period could impact investor sentiment. Therefore, while the data is promising, cautious optimism is advised.

Study demonstrated highly significant and sustained reductions in Lp(a) to week 48

Data support advancing zerlasiran into phase 3 with 300 mg dose

LONDON--(BUSINESS WIRE)-- Silence Therapeutics plc, Nasdaq: SLN (“Silence” or the “Company”), an experienced and innovative biotechnology company committed to transforming people’s lives by silencing diseases through precision engineered medicines, today announced positive topline 48-week data from the ALPACAR-360 phase 2 study of zerlasiran (SLN360) in 178 subjects with baseline lipoprotein(a), or Lp(a), levels at or over 125 nmol/L at high risk of atherosclerotic cardiovascular disease (ASCVD) events. Zerlasiran is a siRNA (short interfering RNA) designed to lower the body’s production of Lp(a), a key genetic risk factor for cardiovascular disease affecting up to 20% of the world’s population.

In the double-blind placebo-controlled treatment period, zerlasiran was administered at 300 mg subcutaneously every 16 or 24 weeks and 450 mg every 24 weeks to patients with a median baseline Lp(a) of approximately 215 nmol/L. These data demonstrated a highly significant reduction from baseline in Lp(a) compared to placebo to 48 weeks (end of treatment and dosing period). Median maximum Lp(a) reduction of approximately 90% or greater was observed for both doses during the treatment period. Zerlasiran was well tolerated with no serious safety concerns. As previously announced, the study met its primary endpoint with a highly significant reduction from baseline in Lp(a) compared to placebo to 36 weeks. The study is ongoing, and patients will be followed through to week 60 (end of study).

“We are encouraged by the strength of the phase 2 data and emerging competitive profile of zerlasiran, which support an infrequent dosing regimen of at least quarterly with the 300 mg dose,” said Steven Romano, MD, Head of Research and Development at Silence. “We look forward to advancing zerlasiran to phase 3 as a potential treatment for this major unmet need in cardiovascular disease.”

The Company plans to provide full results at a future scientific meeting or publication following completion of the study.

About Silence Therapeutics
Silence Therapeutics is developing a new generation of medicines by harnessing the body's natural mechanism of RNA interference, or RNAi, to inhibit the expression of specific target genes thought to play a role in the pathology of diseases with significant unmet need. Silence's proprietary mRNAi GOLD™ platform can be used to create siRNAs (short interfering RNAs) that precisely target and silence disease-associated genes in the liver, which represents a substantial opportunity. Silence's wholly owned product candidates include zerlasiran designed to address the high and prevalent unmet medical need in reducing cardiovascular risk in people born with elevated levels of lipoprotein(a) and divesiran designed to address rare hematological diseases, including polycythemia vera. Silence also maintains ongoing research and development collaborations with AstraZeneca and Hansoh Pharma, among others. For more information, please visit https://www.silence-therapeutics.com/.

Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All statements in this press release other than statements of historical facts are “forward-looking statements. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding: the Company’s clinical development plans of zerlasiran; the assessment of the data from the ALPACAR-360 study of zerlasiran; the efficacy and safety of zerlasiran; the estimated world’s [adult population] who have Lp(a), a key genetic risk factor for cardiovascular disease; the Company’s plans to advance zerlasiran into a Phase 3 registrational program in patients with baseline Lp(a); the potential clinical benefits of zerlasiran; and the Company’s plans to submit additional data from the ALPACAR-360 study for publication at a conference or in a peer-reviewed journal. These forward-looking statements are based on the Company’s expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties that could cause the Company’s clinical development programs, future results or performance to differ materially from those expressed or implied by the forward-looking statements. Many factors may cause differences between current expectations and actual results, including: the potential that success in preclinical testing and earlier clinical trials does not ensure that later clinical trials will generate the same results or otherwise provide adequate data to demonstrate the efficacy and safety of a product candidate; the impacts of macroeconomic conditions, including the conflict in Ukraine and the conflict between Israel and Hamas, heightened inflation and uncertain credit and financial markets, on the Company’s business, clinical trials and financial position; unexpected safety or efficacy data observed during preclinical studies or clinical trials; clinical trial site activation or enrollment rates that are lower than expected; the Company’s ability to realize the benefits of its collaborations and license agreements; changes in expected or existing competition; changes in the regulatory environment; the uncertainties and timing of the regulatory approval process; and unexpected litigation or other disputes. Other factors that may cause the Company’s actual results to differ from those expressed or implied in the forward-looking statements in this press release are identified in the section titled "Risk Factors" in the Company’s Annual Report on Form 20-F for the year ended December 31, 2023 filed with the U.S. Securities and Exchange Commission (the “SEC”) on March 13, 2024 as well as its other documents subsequently filed with or furnished to the SEC. The Company expressly disclaims any obligation to update any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise, except as otherwise required by law.

View source version on businesswire.com: https://www.businesswire.com/news/home/20240620544030/en/

Inquiries:

Silence Therapeutics plc

Gem Hopkins, VP, IR and Corporate Communications

ir@silence-therapeutics.com

+1 (646) 637-3208

Source: Silence Therapeutics plc

FAQ

What is the latest data on Silence Therapeutics' zerlasiran?

Silence Therapeutics announced positive topline 48-week data from its Phase 2 study of zerlasiran, showing a 90% or greater reduction in Lp(a) levels.

What were the dosages used in the Phase 2 study of zerlasiran?

In the Phase 2 study, zerlasiran was administered at doses of 300 mg subcutaneously every 16 or 24 weeks and 450 mg every 24 weeks.

How effective was zerlasiran in reducing lipoprotein(a) levels?

The Phase 2 study demonstrated a highly significant median reduction of approximately 90% or greater in Lp(a) levels from baseline.

Were there any safety concerns in the Phase 2 study of zerlasiran?

Zerlasiran was well tolerated with no serious safety concerns reported in the Phase 2 study.

What is the next step for zerlasiran after the Phase 2 study?

Silence Therapeutics plans to advance zerlasiran to Phase 3 trials following the positive results from the Phase 2 study.