Zilebesiran by Alnylam Pharmaceuticals: status and timeline

Zilebesiran

Show that steady, round-the-clock blood pressure control from two shots a year cuts heart attacks, strokes, heart failure and cardiovascular deaths in people whose pressure stays high on standard pills.

PilotStage 3 of 5

In the 11,000-patient ZENITH outcomes trial with Roche; first patient dosed Oct 2025.

Updated 1 Oct 2025Checked 11 Oct0 updates this week

Milestones

Next · Enrol ~11,000 patients in 35 countries

Roche partnership: Roche pays 60% of development24 Jul 2023Complete.
KARDIA-1: up to 16.7 mmHg lower 24-hour pressureNov 2023Complete.
KARDIA-2: adds up to 12.1 mmHg on top of standard pills7 Apr 2024Complete.
KARDIA-3 results at ESC; move to Phase 3 decided30 Aug 2025Complete.
First patient dosed in ZENITH outcomes trial1 Oct 2025Complete.
Enrol ~11,000 patients in 35 countriesTarget 2026Current milestone.

Most important updates

Upcoming

2026Enrol ~11,000 patients in 35 countries (next)

Current obstacles

Smaller effect in the sickest patientsIn KARDIA-3, high-risk patients on several drugs saw only a 5.0 mmHg office drop at 300 mg; the 600 mg dose missed significance.
Proving fewer heart attacks and strokesLower pressure alone may not win broad use. ZENITH must show fewer cardiovascular events, which takes thousands of patients and years.
Potassium and kidney signalsKARDIA-2: high potassium in 3.2-6.8% of treated patients (1.3-1.7% confirmed); 8.5-12.7% had a 30%+ kidney-filtering dip, mostly mild and brief.

Physics limits

Blocking one pressure system has a ceilingBlood pressure is set by several overlapping systems: nerves, kidneys, salt and vessel stiffness. Shutting one hormone chain lowers pressure only so far, which is why it works best combined with a diuretic.
This hormone chain also guards potassium and kidneysThe same hormones help the kidneys keep filtering and control potassium. Turning them down strongly can raise potassium or reduce filtering, especially in people with weak kidneys.
A long-acting drug can't be switched off fastMonths of gene silencing are the selling point, but if pressure drops too low during illness or dehydration, the effect can't be withdrawn quickly; doctors must counter it with other measures.

How it works

3 parts

Target

Cut the supply at the source

Angiotensinogen, made in the liver, is the first link in the hormone chain that tightens blood vessels and holds salt. Less of it means lower pressure.

RNAi

Silencing the gene's message

A short double-stranded RNA makes liver cells destroy the messenger copy of the angiotensinogen gene, so the protein is not built. Levels fell 88-98%.

Duration

Two shots a year

One injection keeps working for months, giving steady 24-hour control instead of daily pills that patients often skip or that wear off overnight.

Spec sheet

Spec	Zilebesiran
Phase 3 dose	300 mg every 6 months^R (reported)
Angiotensinogen cut (KARDIA-1)	88-98%^R (reported)
24-h systolic drop, 300 mg (KARDIA-1)	16.7 mmHg vs placebo at 3 months^R (reported)
Added drop on a diuretic (KARDIA-2)	12.1 mmHg vs placebo at 3 months^R (reported)
Office drop, high-risk (KARDIA-3)	5.0 mmHg vs placebo at 3 months^R (reported)
ZENITH trial size	~11,000 patients, 35 countries^R (reported)

^R reported by the company

Update log

4 updates

About Alnylam Pharmaceuticals

The team behind Zilebesiran

Alnylam Pharmaceuticals

RNA interference, RNAi medicines, Amvuttra, TTR amyloidosis

Alnylam develops RNAi therapeutics that silence disease-causing genes. Amvuttra exceeded $1B quarterly revenue in Q2 2026.

Alnylam commercialized RNAi technology, filing four approved medicines by 2023.
Amvuttra hit $1.01B quarterly revenue in Q2 2026, up 106%, about 15 months after ATTR-CM launch.
Pipeline includes next-gen nucresiran, mivelsiran (Alzheimer's), and programs for diabetes, obesity.

alnylam.com (opens alnylam.com)Company profile →

Founded: 200224 yrs
Headquarters: United States
Status: Public
Valuation: public
Staff: ~2,500
Works in: BiotechRNA medicines
Coverage: 3 programs · 8 updateslatest 3 Aug 2026checked 10 Oct
Partners: Roche (opens roche.com)Regeneron (opens regeneron.com)Inceptive (opens inceptive.co)
People: Yvonne Greenstreet (opens investors.alnylam.com)Chief Executive Officer

Spec

Zilebesiran

Phase 3 dose

300 mg every 6 months^R (reported)

Angiotensinogen cut (KARDIA-1)

88-98%^R (reported)

24-h systolic drop, 300 mg (KARDIA-1)

16.7 mmHg vs placebo at 3 months^R (reported)

Added drop on a diuretic (KARDIA-2)

12.1 mmHg vs placebo at 3 months^R (reported)

Office drop, high-risk (KARDIA-3)

5.0 mmHg vs placebo at 3 months^R (reported)

ZENITH trial size

~11,000 patients, 35 countries^R (reported)

Zilebesiran

Milestones

Most important updates

Upcoming

Current obstacles

Physics limits

How it works

Cut the supply at the source

Silencing the gene's message

Two shots a year

Spec sheet

Update log

Wed 1 Oct 2025

Sat 30 Aug 2025

Sun 7 Apr 2024

Nov 2023

About Alnylam Pharmaceuticals

Current obstacles

Physics limits

How it works

Cut the supply at the source

Silencing the gene's message

Two shots a year

Spec sheet

Update log

Wed 1 Oct 2025

Sat 30 Aug 2025

Sun 7 Apr 2024

Nov 2023

About Alnylam Pharmaceuticals