Pharma Update
Zilebesiran with best-in-disease potential in hypertension
New MoA with tight upstream blockade of AGT pathway and strong early results
Zilebesiran (siRNA targeting AGT)
Alnylam
Roche
PHARMACEUTICALS
AGT
Zilebesiran
No AGT
synthesis
0
Renin
Angl
Angli
나이
ABPM
ACE
GO
ABPM
Aldosterone
09
००
Serum AGT change from baseline %
-40-
-60-
-80-
-100-
0
Ph I results in hypertension¹
Change in serum angiotensinogen
Mean change in 24-h ambulatory diastolic and
systolic blood pressure
Placebo 10 mg A25 mg 450 mg +100 mg *200 mg 400 mg ▶800 mg
Week 8
Week 24
+
Change from Baseline (mm Hg)
30-
30-
25-
15-
15-
10-
10-
5- 0.5
1.1
5-
0-
0-
-5-
-5-
-10-
-10-
-5.6
-15-
-7.9
-15-
-5.4
-20-
-10.9
-10.4
-9.0
-20-
-5.7
-25-
-25-
-12.5
-9.3
-10.8
-30-
-30-
-35-
-40-
-16.8
-35-
-22.5
-40
Placebo
(N=27)
Zilebesiran,
200 mg
(N=7)
Zilebesiran,
400 mg.
(N=8)
Zilebesiran,
800 mg
(N=8)
Zilebesiran,
200 mg
(N=6)
Zilebesiran,
400 mg
(N=8)
Zilebesiran,
800 mg
(N=8)
12
24
Study week
Diastolic blood pressure
Systolic blood pressure
• siRNA targeting angiotensinogen, the
precursor of all angiotensin peptides may
avoid RAAS escape
• Consistent + durable blood pressure control
with potential for improved adherence
• Positive Ph I results:
>90% reduction of serum AGT for up to 6 months at single SC dose of zilebesiran ≥100mg
Decreases in systolic blood pressure (>10 mm Hg) and diastolic blood pressure (>5 mm Hg) by week 8
and sustained at 24 weeks at single SC dose of zilebesian ≥200mg
• Well tolerated, only mild-to-moderate injection site reactions and no TRAES, hypotension or significant
alterations of renal/liver function
1 Desai et al. N Engl J Med 2023;389:228-38; MoA-mode of action; siRNA-small interfering RNA; SC=subcutaneous; RAAS-renin angiotensin aldosterone system; AGT-angiotensinogen; Angl/II-angiotensin I/II;
ACE-angiotensin-converting enzyme; ABPM-ambulatory blood pressure monitoring; SoC-standard of care; TRAES-treatment related serious adverse events; zilebesiran in partnership with Alnylam Pharmaceuticals
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