LEQVIO (Inclisiran) is a small interfering RNA that inhibits PCSK9, which normally breaks down LDL receptors in the liver, leading to increased LDL cholesterol levels. Inclisiran is administered as two initial doses within 3 months, followed by twice yearly doses, to lower LDL cholesterol in adults with atherosclerotic cardiovascular disease who are already taking statins. By silencing the PCSK9 gene, inclisiran prevents PCSK9 from reducing LDL receptors on liver cells, allowing more LDL cholesterol to be removed from the bloodstream. Clinical trials showed inclisiran reduced LDL cholesterol by 50% compared to placebo when added to statin therapy.

1. LEQVIO (Inclisiran)
Presented by Suraj Mungase
Department of Pharmacy Practice
M Pharm 2nd sem

2. Flow of presentation
● What is LEQVIO ?
● What is (ASCVD)?
● What is PCSK9?
● What is mechanism of action?
● Effect of drug on pregnancy
● Reference

3.  Leqvio is a small interfering RNA (siRNA) that inhibits the
PCSK9( proprotein convertase subtilism –kexin Type 9).
 PCSK9 is a novel, well-validated target for lowering LDL
cholesterol.
 Inclisiran is an injectable medicine used along with diet & other
lipids lowering agents in adults with( ASCVD )
 Generally given to patients who already had previous
cardiovascular events to reduce the chance of having another.

4. What is (ASCVD)?
● Atherosclerotic cardiovascular disease.
● The build-up of fats and cholesterol plaque in the walls of arteries.
● Arteries are the blood vessels who carry blood to all over the body ,
which are lined by thin-layer cells called the endothelium.
● Atherosclerosis begins with the damage of the endothelium.
Obstruction of blood flow
Decrease blood supply to heart muscles

5. The heart is unable to pump the blood.
Heart attacks, stroke, angina
Causes: High cholesterol ( especially LDL-C )
Obesity
Smoking
Stress
Recommended LDL-C level for people with ASCVD is less than
70mg/dL

6. What is PCSK9?
● Proprotein convertase subtilisin-kexin type 9.
● Low–density lipoprotein receptors are present on the cells
surface plays a critical role in regulating blood cholesterol
levels
● LDL receptor is abundant in the liver (the organ responsible
for removing most excess cholesterol from the body)
● PCSK9 breaks down the LDL protein receptors before
reaching the cell surface.
● So LDL level is increased in bloodstream.

7. Mechanism of action
Interaction between GalNAc & ASPGR
The inclusion of the ASPGR/Inclisiran complex into endosomes
where a double strand of inclisiran is released into the cytoplasm
of the liver cell.
A free double strand of inclisiran is caught by the RNA-induced
silencing complex & sense strand is released.

8. mRNA of PCSK9 enters the cytoplasm where it interacts with the
corresponding antisense strand of inclisiran
The RNA induced silencing complex(RISC) destroys the m RNA of
PCSK9
Decrease the synthesis of PCSK9

9. Mechanism of action of leqvio

10. Dosage & administration
C/I
None
Limitation of use
The effect of LEQVIO on cardiovascular
morbidity and mortality has not been
determined.
Adverse reaction
Common adverse reactions in
clinical trials :
Injection site reaction, urinary
tract infection ,
diarrhea,bronchitis, pain in
extremity
The recommended dose of leqvio in
combination with a statin is 284 mg
administered as a single SC injection
initially again at 3 months & then
every 6 months.

11. Pregnancy
Discontinue Leqvio when pregnancy is recognized.
It lowers LDL-C levels in the circulation, thus
decreasing the cholesterol& possibly other
biologically active substances derived from
cholesterol.
Therefore it may cause fatal harm when
administered to a pregnant patient

12. Dosing schedule
That’s 2
doses a
year
Then once
every 6
months
Another 3
months
later
Initial
dose

13. People who intervene with LEQVIO, their LDL-C level is
decreased by 50 % & people who are on placebo, their LDL-C
level is as it is
-60
-50
-40
-30
-20
-10
0
1 2 3 4
Comparision between Statin+Placebo& Statin +LEQVIO
Statin + Placebo Statin+ LEQVIO

14. leqvio
2
Doses a year
together with statin
Other injectable treatments
12 OR
Together with
statin or without
statin
24
Together with
statin or without
statin

15. Is leqvio affordable?
●
For 1 dose =3250$ =248535₹
●
After 1 year=6500$=497071₹

17. REFERENCE
● https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/2
14012lbl.pdf
● https://www.bhf.org.uk/informationsupport/heart-matters-
magazine/medical/inclisiran-new-cholesterol-drug#Heading2