Bempedoic 

Acid for Treating

Hypercholesterolemia
Presented By:

Samar Al-Omair, B.Sc

Contents:

• Hypercholesterolemia
• Bempedoic acid
• Approval status
• Availability
• Mechanism of action
• Adverse effects
• Advantage over statin
• Clinical trials on Bempedoic acid
• Conclusion
• References

2
Hypercholesterolemia

• Hypercholesterlomia is a form of hyperlipidemia, and

hyperlipoproteinemia.

• Cholesterol is transported in the blood plasma within protein

particles (lipoproteins).

• Cholesterol is required for various body functions including the

synthesis of cell membranes.

3
Hypercholesterolemia (Cont.)

• Too high level of cholesterol increase the risk of coronary heart

disease.

• High cholesterol is defined as a LDL-cholesterol greater than

190 mg/dl, greater than 160 mg/dl with one major risk factor,
or greater than 130 mg/dl with two cardiovascular risk factors.

4
Cholesterol-lowering drugs

Statins Ezetimibe
Inhibit cholesterol Reduce cholesterol
production  absorption

Bempedoic
acid ???

Niacin Bile acid

in high doses Make liver converts
increase HDL more cholesterol into
cholesterol bile acids
5
Objectives:

• Evaluate the efficacy and safety of bempedoic acid

alone or when added to background lipid-modifying
therapy in patients with a history of statin intolerance
who require additional LDL-C lowering.

• Future recommendations for the role of bempedoic acid

will include whether bempedoic acid can reduce
cardiovascular events in patients with statin
intolerance.

6
Bempedoic acid

• Bempedoic acid is a novel non-statin drug that inhibits

cholesterol biosynthesis in the same pathway as statins.

7
Approval status

•  Bempedoic acid was approved by FDA in February

2020 as an adjunct to diet and maximally tolerated
statin therapy for the treatment of adults with
heterozygous familiar hypercholesterolemia or
established atherosclerotic cardiovascular disease who
require additional lowering of LDL-C.

8
Availability

• Oral dosage form of 180 mg

(branded as NEXLETOL™).

• A fixed-dose combination as 180mg bempedoic

acid/10mg ezetimibe tablets
(branded as NEXLIZET™).

9
Mechanism of action

• Bempedoic acid inhibit the cholesterol synthesis by

inhibiting ATP-citrate lyase (ACL).

10
Adverse effects

• Hyperuricemia and gout symptoms

• A slightly increased risk of tendon rupture
• Upper respiratory tract infection,
• Back pain,
• Abdominal pain or discomfort,
• Bronchitis,
• Pain in extremity,
• Anemia,
• Elevated liver enzymes

11
Advantage over statin

• Bempedoic acid is not associated with muscular

disorder as statin .
• ( lack of active metabolites in skeletal muscles).

12
Examples of
Clinical
Trials on
Bempedoic
Acid

13
Clinical trials

Conclusion :
Bempedoic acid added to
maximally tolerated
statin therapy did not
lead to a higher incidence
of overall adverse events
than placebo and led to
significantly lower LDL
cholesterol levels

14
Clinical trials

Conclusion:
Bempedoic acid
offers a safe and
effective oral
therapeutic option
for lipid lowering
in patients who
cannot tolerate
statins
15
Clinical trials

Conclusion:
Bempedoic acid
seems to have
unfavorable effects on
serum uric acid,
creatinine level and
the incidence of gout
16
Clinical trials

Conclusions:
The Bempedoic acid and
ezetimibe fixed-dose
combination
significantly lowered
LDL-cholesterol versus
placebo or other oral
monotherapies 
This combination had
favorable safety profile

17
CLEAR cardiovascular outcomes trial

• Is a phase 3, event-driven, randomized, multicenter, double-blind,

placebo-controlled trial.

• Designed to evaluate whether treatment with Bempedoic acid

reduces the risk of cardiovascular events.

Actual Study Start November 18, 2016

Date  :
Estimated Study December 2022
Completion Date  :

18
Conclusion

• Bempedoic acid is a novel class of non-statin therapy that targets

hepatic cholesterol.

• It demonstrated significant LDL-c lowering ability as

monotherapy and in combination with ezetimibe.

• If long term safety are favorable, Bempedoic acid will improve

cardiovascular risk prevention in statin-intolerant patients.

19
References
1. Ibrahim MA, Asuka E, Jialal I. Hypercholesterolemia. [Updated 2020 Aug 30]. In:
Statpearls [Internet]. Treasure Island (FL): Statpearls Publishing; 2020 Jan-. Available
from: https://www.ncbi.nlm.nih.gov/books/nbk459188/
2. Mandal A. 2019. Hypercholesterolemia Treatment. News-medical, Accessed 26 October
2020. Available from: https://www.news-medical.net/health/hypercholesterolemia-
treatment.aspx
3. Ogbru O and  Marks JW. 2019. Bile Acid Sequestrants. Medicine Net, Accessed 26
October 2020. Available from:
https://www.medicinenet.com/bile_acid_sequestrants/article.htm#how_do_bile_acid_se
questrants_work
4. Tibuakuu M ,  Blumenthal RS,  Martin SS. 2020. Bempedoic Acid For LDL-C
Lowering: What Do We Know? Accessed 25 October 2020. Available from:
https://www.acc.org/latest-in-cardiology/articles/2020/08/10/08/21/bempedoic-acid-for-
ldl-c-lowering
5. Ballantyne CM, Laufs U, Ray KK, et al. Bempedoic Acid Plus Ezetimibe Fixed-dose
Combination In Patients With Hypercholesterolemia And High CVD Risk Treated
With Maximally Tolerated Statin Therapy. Eur J Prev Cardiol. 2020 Apr;27(6):593-
603. Doi: 10.1177/2047487319864671. 
20
Thank you for your attention.

ANY Questions?

21