Silence Therapeutics Announces JAMA Publication of Additional Phase 1 Data for Zerlasiran in Subjects with Elevated Lipoprotein(a)

Rhea-AI Summary

Silence Therapeutics plc, Nasdaq: SLN, announced positive results from the APOLLO phase 1 study of zerlasiran in reducing Lp(a) levels, a genetic risk factor for cardiovascular disease. The findings, published in JAMA, show sustained reductions in Lp(a) concentrations with well-tolerated profiles, promising advancements in addressing cardiovascular disease.

Medical Research Analyst

The recent publication of phase 1 study results for zerlasiran, an siRNA therapeutic aimed at reducing Lp(a) levels, presents a significant development in the field of cardiovascular disease treatment. The study's findings indicate that zerlasiran has a favorable safety profile and efficacy in lowering Lp(a), a genetic risk factor for cardiovascular conditions. Given that up to 20% of the global population is affected by elevated Lp(a) levels, the potential market for such a treatment is substantial.

The data showing sustained reductions in Lp(a) concentrations over a year for high doses and over 201 days for multiple dosing regimens in patients with atherosclerotic cardiovascular disease (ASCVD) suggests that zerlasiran could offer a long-term management solution for patients at risk. This could lead to a paradigm shift in how cardiovascular risk is managed, particularly for patients who do not respond to traditional lipid-lowering therapies.

From a medical research perspective, the use of siRNA technology in this context is noteworthy. It represents a growing area of interest in precision medicine, where treatments are designed to target specific genetic pathways. The success of zerlasiran in clinical trials could catalyze further investment and innovation in siRNA-based therapies.

Financial Analyst

The publication of positive phase 1 study results for zerlasiran in a prestigious journal like JAMA is likely to have favorable implications for Silence Therapeutics' stock performance. Investors often respond well to clinical milestones, especially those published in reputable medical journals, as they validate the scientific progress of a company's pipeline.

Considering the potential market size, due to the prevalence of high Lp(a) levels in the population, the successful development of zerlasiran could lead to significant revenue streams for Silence Therapeutics. However, it is essential to consider the cost of ongoing clinical trials, potential regulatory hurdles and the time frame until market approval when evaluating the financial impact.

Long-term implications for stakeholders include the positioning of Silence Therapeutics as a leader in precision medicine for cardiovascular diseases. Should zerlasiran reach the market, it could also impact the competitive landscape, possibly affecting the stock prices of companies with competing therapies.

Market Research Analyst

The positive outcome of the APOLLO phase 1 study for zerlasiran highlights a significant unmet need in the treatment of cardiovascular diseases associated with high Lp(a) levels. As the current treatment options are limited, a new and effective drug like zerlasiran could capture a considerable share of the cardiovascular disease treatment market.

Market research indicates that patient-centric treatments with fewer side effects and long-term benefits are highly sought after. Zerlasiran's well-tolerated profile and sustained efficacy align with these market demands, potentially leading to strong adoption rates upon commercialization. Additionally, as a precision engineered medicine, zerlasiran could benefit from favorable reimbursement policies, especially in markets with a high focus on innovative treatment solutions.

The interest in personalized medicine is growing and zerlasiran's development aligns with this trend. The market for such targeted therapies is expected to expand, providing opportunities for companies like Silence Therapeutics to establish a strong presence and potentially collaborate with larger pharmaceutical firms.

Published findings demonstrate zerlasiran was well-tolerated and significantly reduced Lp(a) after single and multiple dosing

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 additional results from the APOLLO phase 1 study of zerlasiran (SLN360) in subjects with baseline lipoprotein(a), or Lp(a), levels at or over 150 nmol/L were published in the Journal of the American Medical Association (JAMA), linked here.

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.

“Positive phase 1 data published in JAMA demonstrate treatment with zerlasiran produced sustained reductions in Lp(a) concentrations with a well-tolerated profile using varying dosing regimens,” said Curtis Rambaran, MD, Chief Medical Officer at Silence and senior author of the publication. “The promising findings from this study are particularly encouraging as we complete the phase 2 study for zerlasiran and underscore our commitment to address this major unmet need in cardiovascular disease.”

The single ascending and multiple dose trial enrolled 32 healthy participants and 36 patients with atherosclerotic cardiovascular disease (ASCVD) and Lp(a) concentrations ≥150 nmol/L. Results from the single ascending dose portion of the trial in healthy participants were previously published in the April 2022 issue of JAMA, linked here. Today’s JAMA publication reviews findings from the extended 365 day follow up of healthy participants who received the two highest zerlasiran doses (300 or 600 mg) and 201 days of follow up for ASCVD patients administered 2 doses.

Healthy participants were randomized and received a single subcutaneous dose of placebo, 300 mg or 600 mg; ASCVD patients received two doses of placebo, 200 mg at a 4-week interval or 300 mg or 450 mg at an 8-week interval. The primary outcome was safety and tolerability. Secondary outcomes included the serum levels of zerlasiran and effects on Lp(a) serum concentrations.

Zerlasiran was safe and well tolerated. The median change from baseline in serum Lp(a) concentrations 365 days after single doses for placebo, 300 mg, and 600 mg were +14%, −30%, and −29% respectively. The maximal median change from baseline after two doses of placebo, 200 mg, 300 mg and 450 mg were +7%, -97%, -98% and -99%, attenuating to 0.3%, -60%, 90% and 89% respectively, after 201 days.

Zerlasiran is currently being evaluated in the ALPACAR-360 phase 2 study in subjects with baseline Lp(a) levels at or over 125 nmol/L at high risk of ASCVD events.

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 high levels of lipoprotein(a) and divesiran designed to address 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

Certain statements made in this announcement are forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995 and other securities laws, including with respect to the Company’s cash runway and forecast operating cash flow, the Company’s clinical and commercial prospects, regulatory approvals of the Company’s product candidates, potential partnerships or collaborations or payments under new and existing collaborations, the initiation or completion of the Company’s clinical trials and the anticipated timing or outcomes of data reports from the Company’s clinical trials. These forward-looking statements are not historical facts but rather are based on the Company's current assumptions, beliefs, expectations, estimates and projections about its industry. Words such as “anticipate,” “expect,” “intend,” “plan,” “believe,” “seek,” “estimate,” and similar expressions are intended to identify forward-looking statements. These statements are not guarantees of future performance and are subject to known and unknown risks, uncertainties, and other factors, some of which are beyond the Company's control, are difficult to predict, and could cause actual results to differ materially from those expressed or forecasted in the forward-looking statements, including those risks identified in the Company’s most recent Admission Document and its Annual Report on Form 20-F filed with the U.S. Securities and Exchange Commission on March 13, 2024. The Company cautions security holders and prospective security holders not to place undue reliance on these forward-looking statements, which reflect the view of the Company only as of the date of this announcement. The forward-looking statements made in this announcement relate only to events as of the date on which the statements are made. The Company will not undertake any obligation to release publicly any revisions or updates to these forward-looking statements to reflect events, circumstances, or unanticipated events occurring after the date of this announcement except as required by law or by any appropriate regulatory authority.

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Inquiries:



Silence Therapeutics plc

Gem Hopkins, VP, IR and Corporate Communications

Tel: +1 (646) 637-3208

ir@silence-therapeutics.com



Media Relations

MKC Strategies

Mary Conway

Tel: +1 (516) 606-6545

mconway@mkcstrategies.com

Source: Silence Therapeutics plc

FAQ

What is the purpose of the APOLLO phase 1 study of zerlasiran (SLN360)?

The purpose of the study is to lower the body's production of Lp(a), a genetic risk factor for cardiovascular disease, through precision engineered medicines.

Where were the results of the APOLLO phase 1 study published?

The results were published in the Journal of the American Medical Association (JAMA).

What were the primary outcomes of the single ascending and multiple dose trial of zerlasiran?

The primary outcomes were safety and tolerability, with secondary outcomes focusing on serum levels of zerlasiran and effects on Lp(a) serum concentrations.

What were the median changes from baseline in serum Lp(a) concentrations after single and multiple doses of zerlasiran?

After single doses, the median changes were +14% for placebo, -30% for 300 mg, and -29% for 600 mg. After two doses, the changes were +7% for placebo, -97% for 200 mg, -98% for 300 mg, and -99% for 450 mg.

Which phase is zerlasiran currently being evaluated in?

Zerlasiran is currently being evaluated in the ALPACAR-360 phase 2 study in subjects with baseline Lp(a) levels at or over 125 nmol/L at high risk of ASCVD events.