Eli Lilly Launches Phase 3 Trial in China for Lepodisiran, a Twice-Yearly RNAi Therapy Targeting Cardiovascular Disease

Jul 02, 2024 15:30 CST Updated 15:31

Eli Lilly

Global Pharmaceutical R&D and Production Company

▎Edited by the WuXi AppTec content team

The latest disclosure from the China Drug Clinical Trial Registration and Information Disclosure Platform shows,Eli Lilly and Company has launched alepodisiran（LY3819469）TheInternational Multicenter (including China) Phase 3 Clinical Study, Indication:InAccompanying Elevated Lipoprotein(a) Levels in Diagnosed Atherosclerotic Cardiovascular Disease (ASCVD)Assessment of Lepodisiran in Adult Patients at Risk of Elevated First Cardiovascular EventsReduceRisk of Major Adverse Cardiovascular Events (MACE).ThisThe study plans to enroll 700 participants in China and 12,500 participants internationally.In terms of drug administration,lepodisiran400mg subcutaneous injection, once every 6 months.

Public information shows that lepodisiran is aGalNAc-conjugated small interfering RNA (siRNA) drugs.In the first human study results previously announced by Eli Lilly, a single dose of lepodisiran was shown to safely, potently, and durably (up to 337 days) reduce serum Lp(a) levels in subjects compared to placebo. In the 608mg dose group, subjects experienced a significant reduction in Lp(a) levels.The maximum median reduction reached 97% at Week 48.

Screenshot source:China Drug Clinical Trial Registry and Information Disclosure Platform

RNAi TherapyIt has become one of the important directions in the field of innovative drug research and development.In 2018, Eli Lilly and Company partnered with Dicerna, a company focused on developing RNAi therapies (which has since beenNovo NordiskApproximately USD 3.3 billionAcquisition) Reach a global licensing and R&DCooperation, leveraging the latter's proprietary GalXC RNAi platform to develop the next generation of RNAi therapies,Focus on Potential New Therapies in Cardiometabolic Diseases, Neurodegenerative Diseases, and Pain FieldsThe research and development and commercialization, the two parties plan to cooperate with a target of over 10 targets.

LepodisiranIt is precisely the second product jointly developed by the two parties.RNAi TherapyLaw, thisYesATargetedLPAGeneticSmall interfering RNA, itsBy disrupting the production of apolipoprotein in the liver(a)mRNA to reduceLipoprotein(a) [Lp(a)]The production,Being studied for the treatment ofAtherosclerotic Cardiovascular Disease (ASCVD)。A large number of studies have shown that even if the level of low-density lipoprotein cholesterol (LDL-C) in patients with atherosclerotic cardiovascular disease is effectively reduced, Lp(a) will still increase the risk of future cardiovascular disease. Therefore,Targeting Lp(a) as a new therapeutic target holds significant clinical importance.。

November 2023, Eli Lilly and CompanyAt the American Heart Association Scientific SessionThe first-in-human study results of lepodisiran were published.48 participants with an average Lp(a)Volunteers with a level of 110 nmol/L receivedOne subcutaneous injectionAmong them, 12 were randomly assigned to receive a placebo, and 36 received different doses of lepodisiran. The main results showed:

Drug levels rose rapidly and returned to baseline within 48 hours, indicating a swift transfer of the drug from the bloodstream to the liver.
At the highest dose (608mg) of lepodisiran, Lp(a)Rapid decline in levels,Became undetectable on Day 29, remaining undetectable from day 29 to day 281, then slightly increasing,At 48 weeks, Lp(a)The horizontal median decreased by 94%.Maximum Median Change97%。
At lower doses of lepodisiran, Lp(a)The duration of the reduction was shortened, but in patients receiving the 304 mg dose, it was still maintained at 48 weeks.75%The decline.

The studyThe results showed that,A single injection of lepodisiran reduces Lp(a)The level has dropped to undetectable levels within the past year.This important research finding was simultaneously published in the authoritative medical journal, *The Journal of the American Medical Association* (JAMA).

Atherosclerotic Cardiovascular Disease (ASCVD) is a general term for a series of diseases based on atherosclerosis as the pathological foundation and is one of the leading causes of disability and mortality worldwide. Over the past several years, despite continuous attempts by researchers to find new and effective treatments, millions of people are still suffering from the pain and distress caused by ASCVD. It is hoped that Eli Lilly's RNAi therapy under research will proceed smoothly in subsequent studies and achieve positive results, bringing new treatment options to patients as soon as possible.

References:

[1] China Drug Clinical Trial Registration and Information Disclosure Platform. Retrieved Jun 25，2024, From http://www.chinadrugtrials.org.cn/index.html

[2] One dose of experimental therapy reduced lipoprotein(a) more than 94% for nearly a year. Retrieved November 13, 2023, from https://newsroom.heart.org/news/one-dose-of-experimental-therapy-reduced-lipoprotein-a-more-than-94-for-nearly-a-year

[3] Steven E. Nissen et al., Lepodisiran, an Extended-Duration Short Interfering RNA Targeting Lipoprotein(a): A Randomized Dose-Ascending Clinical Trial. JAMA. doi:10.1001/jama.2023.21835

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