AstraZeneca’s Dapagliflozin (Forxiga) approved in India for treatment of patients with Heart Failure

Dapagliflozin (Forxiga) is the first SGLT-2 inhibitor proven to significantly reduce the risk of Cardiovascular death and hospitalisation for heart failure in patients with HFrEF.

AstraZeneca Pharma India Limited (AstraZeneca India), a leading science-led biopharmaceutical company, today received the Marketing Authorization for Dapagliflozin (Forxiga),  for the treatment of patients with heart failure with reduced ejection fraction (HFrEF). This is the first in class SGLT-2 inhibitor drug approved for the treatment of  HFrEF and is the first drug proven to significantly reduce the risk of Cardiovascular death and hospitalisation for Heart Failure in patients with HFrEF.

The approval follows positive results from the landmark Phase III DAPA-HF trial,  that proved that Dapagliflozin in addition to standard of care, reduced the risk of the composite outcome of Cardiovascular death or the worsening of Heart Failure versus placebo by 26%.¹   About one-fourth patients in the study population were  from Asian region including India.

Heart failure is a life threatening disease in which the heart muscle is unable to pump enough blood to meet the body’s needs for blood and oxygen².It affects around ~6.4 crore people worldwide (at least half of which have reduced ejection fraction), including at least 8 to 10  million patients in India³. It is a chronic, degenerative  disease where half of patients die within five years of diagnosis. Heart Failure remains as fatal as some of the most common cancers in both men (prostate and bladder cancers) and women (breast cancer) ⁴. It is the leading cause of hospitalisation for those over the age of 65 and represents a significant clinical and economic burden⁵.  Further, the mean age of  Heart Failure is 61.2 years in Indians,  atleast a decade  earlier than western population.^3,4,5

Gagandeep Singh, Managing Director, AstraZeneca Pharma India Limited said, “ Heart Failure is a serious health condition that affects ~6.4 crore people worldwide and at least 8–10 million in India. The accelerated regulatory approval in India will provide the much-needed treatment to help patients reduce their disease burden & live longer”

Dr. Anil Kukreja, Vice President – Medical Affairs & Regulatory, AstraZeneca India said, “Despite currently available therapies for management of Heart failure,  significant unmet needs exist globally as well as in India. This approval for Dapaglifozin (Forxiga) based on significant and clinically meaningful results from Dapa-HF trial provides much required confidence on a novel pharmacological approach, first in class SGLT2 inhibitor, for management of patients with HFrEF. This approval is boon for HFrEF patients in India where considerable efforts are required to address significant unmet needs of frequent hospitalization, urgent visits to hospital emergency room and cardiovascular death in HF patients despite available therapies ”

The U.S. Food and Drug Administration approved Dapagliflozin to be used in management of patients with heart failure with reduced ejection fraction. The Canadian Cardiovascular Society has updated their guidelines  and recommend the use of SGLT2i drugs like Dapagliflozin to manage heart failure  to provide better patient care.

Dapaglifozin (Forxiga) is also indicated as an adjunct to diet and exercise to improve glycaemic control in adults with T2D in India. The drug is also approved for reduction of risk of hospitalisation due to Heart failure in Type 2 Diabetes patients with high risk factors.

The current estimates about incidence of HF in India vary widely from 8 to 10 million  with HFrEF being  predominantly observed in 53% of population^3,6. Indian patients present with HF at a younger age⁶.Prevalence of hypertension and diabetes as comorbidities are very high⁶. Hospital-stay in Indian HF patients is higher due to higher prevalence of comorbidities⁶. Prognosis of HF in Indian patients appears to be worse with In-hospital mortality of 9.7%,⁴ One-year mortality of 23%⁸ and 3 years the mortality of 44.8%.⁴ Optimal therapy (OMT) could be initiated in less than 50% of HF patients (BB-48.8%, ACEI/ARB-47.6%) due to multiple comorbidities in Indian patients⁹.

1. Detailed results from Phase III DAPA-HF trial showed Farxiga significantly reduced both the incidence of cardiovascular death and the worsening of heart failure. Accessed from: https://www.astrazeneca.com/media-centre/press-releases/2019/detailed-results-from-phase-iii-dapa-hf-trial-showed-farxiga-significantly-reduced-both-the-incidence-of-cardiovascular-death-and-the-worsening-of-heart-failure-01092019.html
2. Mayo Clinic. Heart failure; 2017 [cited 2019 Aug 14]. Available from URL: https://www.mayoclinic.org/diseases-conditions/heart-failure/symptoms-causes/syc-20373142.
3. Vos T et al. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. The Lancet 2017; 390(10100):1211–59.
4. Mozaffarian D et al. Circulation. 2016 Jan 26;133(4):e38-360 and the CDC: https://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_heart_failure.htm
5. Bhuiyan, Taslima, and Mathew S Maurer. “Heart Failure with Preserved Ejection Fraction: Persistent Diagnosis, Therapeutic Enigma.” Current cardiovascular risk reports vol. 5,5 (2011): 440-449. doi:10.1007/s12170-011-0184-2
6. Mamas, M. A., Sperrin, M., Watson, M. C., Coutts, A., Wilde, K., Burton, C., … Myint, P. K. (2017). Do patients have worse outcomes in heart failure than in cancer? A primary care-based cohort study with 10-year follow-up in Scotland. European Journal of Heart Failure, 19(9), 1095-1104.https://doi.org/10.1002/ejhf.822
7. Dokainish H,  et al. INTER-CHF Investigators. Global mortality variations in patients with heart failure: results from the International Congestive Heart Failure (INTER-CHF) prospective cohort study. Lancet Glob Health. 2017 Jul;5(7):e665-e672.
8. Sanjay G et al. In-Hospital and Three-Year Outcomes of Heart Failure Patients in South India: The Trivandrum Heart Failure Registry. J Card Fail. 2018 Dec;24(12):842-848.
9. Azad N, Lemay G.  Management of chronic heart failure in the older population. J Geriatr Cardiol. 2014;11:329-337.