Forxiga for HF

1. 1
NEW INDICATION
ID-3774 / Oct 2023
2
FORXIGA is the FIRST SGLT2i approved by BPOM, indicated in adults for
the treatment of symptomatic chronic stable heart failure (NYHA functional
class (II-III) with reduced ejection fraction (left ventricular ejection fraction
(LVEF) < 40%), as an adjunct to standard of care therapy. 1
1. FORXIGA Approve Product Information 2 . McMurray JJV et al. N Engl J Med. 2019;381(21):1995–2008.3. ESC
Guideline 2021.

2. New Indication
FORXIGA® is THE FIRST AND ONLY SGLT2i approved by BPOM, indicated for the treatment of
Symptomatic chronic stable heart failure (NYHA II-III) with reduce ejection fraction, as an adjunct to
standard of care therapy2
1. McMurray JJV et al. N Engl J Med. 2019;381(21):1995–2008. 2. Berg DD et al. JAMA Cardiol. 2021;6(5):499–507

3. 3
NEW INDICATION
ID-3765/Oct 2023
2
FORXIGA is the FIRST SGLT2i approved by BPOM, indicated in adults for
the treatment of symptomatic chronic stable heart failure (NYHA functional
class (II-III) with reduced ejection fraction (left ventricular ejection fraction
(LVEF) < 40%), as an adjunct to standard of care therapy. 1
1. FORXIGA Approve Product Information 2 . McMurray JJV et al. N Engl J Med. 2019;381(21):1995–2008.3. ESC

4. 32% of
patients
Nearly one-third of patients
with HFrEF are at high risk
of hospitalisation or CV death,
including those who appear stable2
Based on NYHA classification over
a 4-year period, from the 2004 CHARM study
Patients with hHF/CV death
Patients event free
HF patients are at very high risk of death and hospitalisation
aBased on a prospective observational study of 3494 US outpatients with chronic HFrEF in the CHAMP-HF registry; bBased on a retrospective analysis of 51,286 patients from a US Military Data Repository admitted to a healthcare facility
for the first time for heart failure. During the 7-year study period (2007–2013), patients were assessed for subsequent hHF, comorbidities,
and mortality data. No distinction was made between patients with reduced or preserved ejection fraction
CV, cardiovascular; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; hHF, hospitalisation for heart failure; NYHA,
New York Heart Association; SoC, standard of care
1. Khariton Y, et al. JACC Heart Fail 2018:6;465–473; 2. Young JB, et al. Circulation 2004;110:26182626; 3. Lin AH, et al. Mil Med 2017;182:e1932–e1937
are symptomatic,
even with current
HF SoC1,a
Each hHF increases
the risk of mortality further3,b
9out of10
PATIENTS

5. Pharmacological treatment of HF in Asian Countries and
Current Common Treatments for HF
1. Ponikowski P, et al. Eur J Heart Fail 2016;37:2129–2200; 2. Reyes, E. B., Ha, J. W., Firdaus, I., Ghazi, A. M., Phrommintikul, A., Sim, D., Vu, Q. N., Siu, C. W., Yin, W. H., & Cowie, M. R. (2016). Heart failure across Asia: Same
healthcare burden but differences in organization of care. International journal of cardiology, 223, 163–167. https://doi.org/10.1016/j.ijcard.2016.07.256 ;
Suboptimal treatment Clinical Inertia
may leads to
Pharmacological
treatment of HF
Indonesia Malaysia Singapore Europe
RAAS inhibitor 78% 67% 74% 89%
β – blocker 32% 72% 65% 87%
Calcium channel blocker - 17% - 10%
Ivabradine - - - -
Diuretic 78% 99% 87% 83%
Digoxin 21% 44% 27% 21%
Lipid-lowering agent - 76% 72% 54%
Anticoagulant - 25% 12% 43%
Pharmacological treatment of HF in some countries or region2
• ACE inhibitor
• ARB
• β blocker
• Loop diuretic
• Mineralocorticoid antagonist
• Sacubitril/valsartan
Current common
treatments for HF1,a

6. The ESC has recognised the benefits of dapagliflozin
in patients with HFrEF
ESC, European Society of Cardiology; HF, heart failure; HFrEF, heart failure with reduced ejection fraction
1. Seferović PM, et al. Eur J Heart Fail 2020;22:1495–1503; 2. McMurray JJV, et al. N Engl J Med 2019;381:1995–2008; 3. Petrie MC, et al. JAMA 2020;323:1353–1368;
4. Solomon SD, et al. JACC Heart Fail 2020;S2213–1779:30254–7 [Epub ahead of print]; 5. Docherty KF, et al. Eur Heart J 2020;41:2379–2392; 6. Dewan P, et al. Eur J Heart Fail 2020;22:1247–1258
“The benefit of dapagliflozin on reducing important clinical events was seen
within weeks of its initiation. Given that HF is associated with severely
impaired survival, a timely initiation of an agent with a proven benefit
on outcomes is of a crucial clinical importance” 1
2020 position statement
Sustained efficacy1 Consistent efficacy
across subgroups2–6
Patients live and feel better

7. Therapeutic algorithm of Class I Therapy Indications for a
patient with heart failure with reduced ejection fraction
European Heart Journal, Volume 42, Issue 36, 21 September 2021, Pages 3599–3726
Dapagliflozin is now
considered to be part of the
management of HFrEF
Class I A

8. 1. McMurray JJV et al. N Engl J Med. 2019;381(21):1995–2008. 2. Berg DD et al. JAMA Cardiol. 2021;6(5):499–507.
In DAPA-HF, dapagliflozin reduced the risk of the primary composite
outcome in patients with HFrEF

9. 1. McMurray JJV et al. N Engl J Med. 2019;381(21):1995–2008.2. McMurray JJV. Oral presentation at the European Society of Cardiology Annual Meeting; 31 August –4 September 2019;
Paris, France. Hot Line Session

10. 1. Petrie MC et al. JAMA. 2020;323(14):1353–1368

11. The KCCQ is a patient self-administered instrument
that measures QoL in patients with HF
KCCQ, Kansas City Cardiomyopathy Questionnaire; HF, heart failure, QoL, quality of life
US Food and Drug Administration. Available at: https://www.fda.gov/media/108301/download#:~:text=KCCQ%20Symptom%20Domain%20quantifies%20the,and%20severity%20are%20also%20available
(Accessed March 2021)
What is the KCCQ?
Self-administered questionnaire
measuring patient perception of HF
impact on six domains:
• Physical function/limitations
• Symptoms
• Symptom stability
• Social interference
• Quality of life
• Self-efficacy
Oedema
Dyspnoea
Fatigue
Shortness of breath
Key HF symptoms

12. Dapagliflozin improved patient QoL from baseline to month 4
and sustained the improvement at month 8
Exploratory post hoc analysis:
Change in KCCQ-OSS from baseline1,a
Patients taking FORXIGA reported a significant
reduction in physical and social limitations,
allowing them to live life more fully1
Time from randomisation
Baseline 4 months 8 months
Secondary endpoint:
Treatment with FORXIGA resulted in a clinically
meaningful benefit over placebo in heart failure
symptoms, as measured by change from baseline
at month 8
in the KCCQ-TSS
(Win ratio: 1.18 [95% CI: 1.11, 1.26]; P<0.0001)2
aThe key secondary endpoint was the KCCQ-TSS. A total of 4443 patients had available KCCQ data at baseline; of these, 4141 and 3955 patients had KCCQ data evaluated at 4 and 8 months, respectively. Treatment with dapagliflozin
resulted in a clinically meaningful benefit over placebo in heart failure symptoms, as measured by change from baseline at month 8 in the KCCQ-TSS (Win ratio: 1.18 [95% CI: 1.11, 1.26]; P<0.0001). A change in 5 points in the KCCQ-OSS
is generally considered to be clinically meaningful
CI, confidence interval; KCCQ, Kansas City Cardiomyopathy Questionnaire; OSS, Overall Summary Score; QoL, quality of life; SoC, standard of care; TSS, Total Symptom Score
1. Kosiborod MN, et al. Circulation 2020;141:90–99; 2. AstraZeneca AB. Forxiga 10 mg EU Summary of Product Characteristics, 2020. Available at: https://www.medicines.org.uk/emc/product/7607/smpc#CLINICAL_PRECAUTIONS
(Accessed March 2021)
Adjusted
mean
KCCQ
score
85
80
75
70
65
60
 1.7439
P<0.0001
 2.3114
P<0.0001
0
Forxiga helped patients feel better and do more
FORXIGA with SoC
Placebo with SoC

13. Data are based on an exploratory post hoc analysis of 4443 patients
CI, confidence interval; ESC, European Society of Cardiology; KCCQ, Kansas City Cardiomyopathy Questionnaire; HFrEF, heart failure with reduced ejection fraction; OR, odds ratio;
QoL, quality of life; TSS, Total Symptom Score
1. Kosiborod MN, et al. Circulation 2020;141:90–99; 2. Seferović PM, et al. Eur J Heart Fail 2020;22:1495–1503
2020 position statement
A sub-analysis of the DAPA-HF trial
demonstrated dapagliflozin can
produce a significant improvement
in quality of life as assessed
by the KCCQ in patients with HFrEF,
which is of high clinical value2
50.9
47.6 48.2
58.30
54.50 54.00
0
10
20
30
40
50
60
70
80
Patients
(%)
≥5 points ≥15 points
≥10 points
P<0.0001 P<0.0001
P<0.0001
OR 1.15
95% CI: 1.08, 1.23
OR 1.15
95% CI: 1.08, 1.22
OR 1.14
95% CI: 1.07, 1.22
Dapagliflozin
Placebo
Improvement in KCCQ-TSS from baseline to month 81
Increase in KCCQ-TSS
Dapagliflozin improved patient QoL from baseline to 8 months

14. Safety and tolerability
considerations

15. Adverse Effect of dapagliflozin1
*Reported in ≥2% of subjects and ≥1% more and at least 3 more subjects treated with dapagliflozin 10 mg compared to placebo.
**Reported by the investigator as possibly related, probably related or related to study treatment and reported in ≥ 0.2% of subjects and ≥ 0.1% more and at least 3 more subjects treated with dapagliflozin 10 mg
compared to placebo
GI: Gastrointestinal; UTI: Urinary Track Infection.
Reference: 1. FORXIGA Approved Product Information
System organ class Very common Common* Uncommon** Rare
Infections and infestations Vulvovaginitis,
balanitis, and related
genital infections*;
UTI*
Fungal infection**
Metabolism and nutrition
disorders
Hypoglycaemia
(when used with SU
or insulin)
Volume depletion;
Thirst**
Diabetic
ketoacidosis
Nervous system disorders Dizziness
GI disorders Constipation**;
dry mouth**
Skin and subcutaneous
tissue disorders
Rash
Musculoskeletal and
connective tissue disorders
Back pain*
Renal and urinary disorders Dysuria polyuria* Nocturia**
Reproductive system
and breast disorders
Vulvovaginal
pruritus**;
pruritus genital**
Investigations ↑ haematocrit;
↓ creatinine renal
clearance during
initial treatment;
dyslipidaemia
↑ blood creatinine;
↑ blood urea**;
↓ weight**

16. 1. McMurray JJV et al. N Engl J Med. 2019;381(21):1995–2008. 2. Forxiga Approved Product Information
≥30 ml/min/1.73m2