# Zilebesiran: A First-in-Class RNAi Therapy for Hypertension

**URL:** <https://www.medboundhub.com/t/zilebesiran-a-first-in-class-rnai-therapy-for-hypertension/8932>\
**Category:** Pharmacy\
**Tags:** drugs, rna-interference, hypertension\
**Created:** [September 25, 2025, 2:00pm UTC](https://www.medboundhub.com/t/zilebesiran-a-first-in-class-rnai-therapy-for-hypertension/8932 "2025-09-25T14:00:41Z")\
**Posts on this page:** 3\
**Page:** 1

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**Author:** ![Nikunj](https://yyz1.discourse-cdn.com/flex033/user_avatar/www.medboundhub.com/nikunj/32/1584_2.png) [@Nikunj](https://www.medboundhub.com/u/Nikunj)\
**Post date:** [September 25, 2025, 2:00pm UTC](https://www.medboundhub.com/t/zilebesiran-a-first-in-class-rnai-therapy-for-hypertension/8932/1 "2025-09-25T14:00:41Z")

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_Zilebesiran_ is an investigational **small interfering RNA (siRNA) therapy** developed by Alnylam pharmaceuticals for **mild to moderate**  **hypertension**.

➡ M.O.A: It targets **angiotensinogen (AGT)** in the liver, suppressing the renin–angiotensin–aldosterone system and lowering blood pressure.

➡ R.O.A: Injected subcutaneously, it offers long-acting control with dosing every 3–6 months.

➡ Results of phase 1 trials: Single doses ≥200 mg produced sustained systolic blood pressure (SBP) reductions (10–20 mmHg) for up to 24 weeks with good tolerability.

[DOI:10.1056/NEJMoa2208391](https://www.nejm.org/doi/full/10.1056/NEJMoa2208391)

➡ Results of phase 2 trials (KARDIA) **:** Doses ranging from 150–600 mg reduced SBP by ~10–20 mmHg versus placebo, both as monotherapy and add-on therapy. Main side effects were mild injection-site reactions.

[doi:10.1001/jama.2024.0728](https://jamanetwork.com/journals/jama/fullarticle/2815379#249517330)

➡ Phase 3 trial however is planned but not yet started.

Since it is a first-in-class medication specifically for hypertension, do you think it will be as popular as other antihypertensives?

MBH/PS

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**Author:** ![Ashwini](https://avatars.discourse-cdn.com/v4/letter/a/b5ac83/32.png) [@Ashwini](https://www.medboundhub.com/u/Ashwini)\
**Post date:** [September 25, 2025, 2:05pm UTC](https://www.medboundhub.com/t/zilebesiran-a-first-in-class-rnai-therapy-for-hypertension/8932/2 "2025-09-25T14:05:16Z")

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Informative

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**Author:** ![Khelaharichandana](https://yyz1.discourse-cdn.com/flex033/user_avatar/www.medboundhub.com/khelaharichandana/32/1634_2.png) [@Khelaharichandana](https://www.medboundhub.com/u/Khelaharichandana)\
**Post date:** [September 25, 2025, 2:54pm UTC](https://www.medboundhub.com/t/zilebesiran-a-first-in-class-rnai-therapy-for-hypertension/8932/3 "2025-09-25T14:54:45Z")

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Informative! thanks for sharing.