dm+d

703678003

Medicine Compliance Aid Stability

ForxigaAstraZeneca UK Ltd

AstraZeneca UK Ltd
Forxiga
Tablets f/c 5mg, 10mg
A2 · Amber 2No stability data is available, the manufacturer does not, or cannot recommend use in CAs but there are no theoretical concerns with the product.
No special precautions for storage
No special precautions for storage
27 February 2015

New Medicines

Forxiga, Edistride (EU), Farxiga (US)Chronic heart failure, with reduced ejection fraction

Information

Forxiga, Edistride (EU), Farxiga (US)
Licence extension / variation
AstraZeneca
AstraZeneca

Development and Regulatory status

Launched
Launched
Launched
November 2020
Nov 20Approved in EU [20].
Oct 20dapagliflozin has been recommended for an extension of its marketing authorisation in the EU for the treatment of symptomatic chronic heart failure with reduced ejection fraction (HFrEF) in adults with and without type-2 diabetes [19].
Oct 20In DAPA-HF, 4742 pts with a baseline eGFR, 1926 (41%) had eGFR <60 ml/min/1.73m2. The effect of dapagliflozin on cardiovascular death or worsening heart failure did not differ by eGFR category (HR in patients with CKD was 0.71 vs 0.77 with eGFR ≥60 ml/min/1.73m2; p=0.54) [17].
May 20Approved by FDA for the treatment of HF in adults with reduced ejection fraction.[16]
Mar 20Also pre-registration in EU [15].
Jan 20Filed in US with priority review to reduce the risk of CV death or the worsening of HF in adults with HFrEF with and without T2D [13].
Sep 19The FDA has granted Fast Track designation in the US for the development of dapagliflozin to reduce the risk of CV death, or the worsening of heart failure, in adults with heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF) [8].
Dec 18Filings planned for 2020 [5].
Mar 18Data from PIII Dapa-HF expected 2019 [4].

Category

SGLT-2 inhibitor
1-2% of the adult population in developed countries have heart failure, with the prevalence rising to 10% in patients 70 years of age or older. Community estimates of prevalence vary from 1.6 to 4.6 cases per 1,000 in men aged 45-74 years and from 0.9 to 2.2 cases per 1,000 in women [3].
Chronic heart failure, with reduced ejection fraction
Oral

Further information

Yes

Trial or other data

Jul 21Analysis of PIII DAPA-HF study (n=4744) reports that extrapolated event-free (gain of 2.1 years; p = 0.002) and overall (1.7 years; p = 0.03) survival time from a primary composite end point event was longer with dapagliflozin compared with placebo for individuals aged 65 years [21].
Oct 20DAPA-HF reports dapagliflozin had only a small effect on systolic blood pressure in patients with heart failure & reduced ejection fraction and was superior to placebo in improving outcomes (worsening heart failure or cardiovascular death) [18].
Oct 20In DAPA-HF, 4742 pts with a baseline eGFR, 1926 (41%) had eGFR <60 ml/min/1.73m2. The effect of dapagliflozin on cardiovascular death or worsening heart failure did not differ by eGFR category (HR in patients with CKD was 0.71 vs 0.77 with eGFR ≥60 ml/min/1.73m2; p=0.54) [17].
Nov 19A late-breaking subanalysis from the PIII Dapa-HF trial presented at the American Heart Association´s Scientific Sessions showed greater cardiovascular (CV) benefit for patients without diabetes than for those with. Dapagliflozin reduced the risk of CV events by 27% vs placebo in non-diabetic patients vs risk reduction of 25% in patients with the disease. Other endpoint results were more mixed. For CV death, dapagliflozin reduced the risk by 21% in patients with diabetes vs 15% in those without, while for heart failure incidents patients with and without diabetes saw a 23% and 38% risk reduction respectively [14].
Nov 19New data from 5 additional analyses of PIII DAPA-HF trial showed FARXIGA reduced risk of worsening heart failure or death from cardiovascular (CV) causes vs. placebo, when added to standard of care (HR 0.73 [95% CI 0.60, 0.88]).[12]
Sep 19First patient commenced dosing in PIII DETERMINE-reduced study. 300 patients will be randomised to dapagliflozin 10mg daily or placebo, recruited from 9 countries. Primary endpoint is change from baseline in 6 minute walking distance at week 16, with data anticipated H1 20 [11].
Sep 19PIII RCT ( NCT03036124; n=4744) found risk of worsening heart failure or death from CV causes was lower among those on dapagliflozin than on placebo (16.3 vs. 21.2%; HR 0.74; 95% CI, 0.65-0.85; p<0.001), regardless of the presence or absence of diabetes; with no difference in risk of hypoglycaemia [10].
Sep 19Data presented at the European Association for the Study of Diabetes annual meeting presented metabolic and safety data that further support use of dapagliflozin in non-diabetic patients. Results showed greater reductions in HbA1c with dapagliflozin among the 45% of DAPA-HF study patients with type 2 diabetes, while in non-diabetic patients it didn’t make a significant impact. Weight loss was demonstrated in both groups, though diabetic patients saw larger reductions on average, measuring 1.6 kg vs 0.6 kg for patients without diabetes. Both groups saw a decrease in systolic blood pressure, and all patients also saw an increase in hematocrit. Side effects such as hypoglycaemia and ketoacidosis only occurred in the diabetes group [9].
Aug 19PIII DAPA-HF trial showed that dapagliflozin met the primary composite endpoint with a statistically-significant and clinically-meaningful reduction of CV death or worsening of heart failure (hospitalisation or urgent heart failure visit), compared to placebo, in patients with reduced ejection fraction (HFrEF) on standard of care treatment, in patients with and without type-2 diabetes [7].
Jun 19Data from PIII Dapa-HF study H2 19 [6].
Dec 18Data from PIII Dapa-HF study expected 2020 [5].
Aug 18Dapa-HF is recruiting patients. Collection of primary outcome data is expected to complete Dec 19 [2].
Aug 18Global PIII Dapa-HF (NCT03036124) study starts. 4,500 patients with CHF will be recruited in 20 countries and will compare dapagliflozin 10mg/5mg plus standrad of care therapy with placebo. Primary endpoint is time to first occurrence of any of the components of a composite of CV death or hospitilisation for HF or an urgent HF visit [1].

Evidence based evaluations

Forxiga, Edistride (EU), Farxiga (US)Chronic kidney disease

Information

Forxiga, Edistride (EU), Farxiga (US)
Licence extension / variation
AstraZeneca
AstraZeneca

Development and Regulatory status

Launched
Launched
Launched
August 2021
Aug 21 Licence extension approved by MHRA and in EU. The new indication is use in adults for the treatment of chronic kidney disease [16]
Jun 21Recommended for EU approval by CHMP – the new indication is “use in adults for the treatment of chronic kidney disease [15].
May 21Approved in US [14]
Jan 21US FDA grant priority review [13].
Dec 20Has been filed to the EMA. AstraZeneca intends to also file to the MHRA [12].
Apr 20Astrazeneca intend to file sNDA H2 20 [8].
Aug 19FDA award fast track designation to Farxiga to delay the progression of renal failure and prevent CV and renal death in patients with CKD.[7]
Dec 18Filings planned for 2021 or later [6].
Mar 18Data from PIII Dapa-CKD expected 2020 [5].
Mar 17PIII study starts [2].

Category

SGLT-2 inhibitor
A large primary care study (practice population 162,113) suggests an age standardised prevalence of stage 3-5 CKD of 8.5% (10.6% in females and 5.8% in males) [1].
Chronic kidney disease
Oral

Further information

Yes

Trial or other data

Sep 20Dapagliflozin is the first SGLT2 inhibitor proven (in the DAPA-CKD trial) to significantly prolong survival of pts with CKD with and without type 2 diabetes [10].
Sep 20PIII DAPA-CKD RCT (n=4304) found that regardless of presence/absence of diabetes, risk of composite of sustained decline in GFR≥ 50%, end-stage kidney disease, or death from renal or CV causes was significantly lower with dapagliflozin vs. placebo (9.2 vs. 14.5%; HR 0.61; 95% CI 0.51-0.72) [11].
Sep 20Further data from the DAPA-CKD trial, which evaluated 4304 pts with 10mg dapaglifozin vs. placebo, show that with standard of care, dapagliflozin decreased the composite measure of worsening of renal function or risk of CV or renal death (primary outcome measure) by 39% vs. placebo. This was in pts with CKD Stages 2-4 and elevated urinary albumin excretion with no differences between pts with/without type 2 diabetes. The trial also hit all secondary endpoints, including a 31% decrease in death from any cause vs. placebo.[10]
Jul 20Data from Dapa CKD trial (n=4304) demonstrated a statistically significant and clinically meaningful effects of dapagliflozin plus std of care. Farxiga 10mg daily vs. placebo in pts with CKD Stages 2-4 and elevated urinary albumin excretion+/- type 2 diabetes resulted in ≥ 50% sustained decline in eGFR, onset of end stage kidney disease (ESKD) or cardiovascular (CV) or renal death in adults with CKD.[9]
Mar 20AstraZeneca announce PIII Dapa-CKD study will be stopped early following a recommendation from an independent Data Monitoring Committee based on its determination of overwhelming efficacy [7].
Dec 17NCT03036150 is currently recruiting; estimated primary completion date Nov 20 [4].
Feb 17PIII (NCT03036150) study to evaluate the effect of dapagliflozin versus placebo, given once daily in addition to standard of care, to prevent the progression of chronic kidney disease (CKD) or cardiovascular (CV)/renal death starts. 4000 adults will be recruited from sites including the US and EU (incl. UK). Collection of primary outcome data (time to first occurrence of any components of the composite (50% or more sustained decline in eGFR or reaching ESRD or CV death or renal death) should complete in Nov 20 [3].

Evidence based evaluations

Forxiga, Edistride (EU), Farxiga (US) Chronic heart failure, with preserved ejection fraction

Information

Forxiga, Edistride (EU), Farxiga (US)
Licence extension / variation
AstraZeneca
AstraZeneca

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials

Category

SGLT-2 inhibitor
1-2% of the adult population in developed countries have heart failure, with the prevalence rising to 10% in patients 70 years of age or older. Community estimates of prevalence vary from 1.6 to 4.6 cases per 1,000 in men aged 45-74 years and from 0.9 to 2.2 cases per 1,000 in women [1].
Chronic heart failure, with preserved ejection fraction
Oral

Evidence based evaluations

Forxiga, Edistride (EU), Farxiga (US) Reduction in risk of hospitalisation with heart failure (HF) and risk of cardiovascular death following acute myocardial infarction (MI)

Information

Forxiga, Edistride (EU), Farxiga (US)
Licence extension / variation
AstraZeneca
AstraZeneca

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
None

Category

SGLT-2 inhibitor
HF is the major cause of death after the acute phase of MI [3]. In 2018-19, there were 74,331 admissions for acute MI [4].
Reduction in risk of hospitalisation with heart failure (HF) and risk of cardiovascular death following acute myocardial infarction (MI)
Oral