AstraZeneca's Farxiga scores FDA nod to cut risk of hospitalization for heart failure in diabetics
While the FDA recently spurned an application to allow AstraZeneca’s blockbuster drug Farxiga for type 1 diabetes that cannot be controlled by insulin, citing safety concerns — the US regulator has endorsed the use of the SGLT2 treatment to reduce the risk of hospitalisation for heart failure in patients with type-2 diabetes and established cardiovascular disease or multiple CV risk factors.
Farxiga is the first SGLT2 in the United States to secure approval in this patient population, AstraZeneca indicated on Monday.
Patients with diabetes are often afflicted with other comorbidities, such as obesity, CV disease, and kidney problems. SGLT2 makers have been clamoring for a broader market share by differentiating their drugs on the basis of therapeutic impact on these intersecting indications — but the major, most lucrative battleground is the heart.
The approval emanates from data tabulated in the DECLARE-TIMI 58 study, which tracked the CV impact of Farxiga versus a placebo over a period of up to five years in more than 17,000 adults. In the trial, the therapy hit one of two primary efficacy endpoints.
The results showed that the Farxiga treatment did trigger a lower rate of hospitalization for heart failure — but the therapy was not better or worse than placebo in its impact on the rate of major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, or ischemic stroke.
On the primary goal of MACE — 8.8% of Farxiga patients and 9.4% in the placebo group suffered MACE events (hazard ratio: 0.93; P=0.17), although the difference was not deemed statistically significant. On the other endpoint, Farxiga did result in a lower rate of cardiovascular death or hospitalization for heart failure (4.9% in the Farxiga arm vs. 5.8% on the placebo group; P=0.005), which reflected a lower rate of hospitalization for heart failure (hazard ratio, 0.73); there was no between-group difference in cardiovascular death.
The FDA approval follows a similar update to the drug’s label by the EMA in August.
Farxiga, akin to Invokana from J&J $JNJ and Jardiance from Eli Lilly $LLY, belongs to a class of diabetes drugs called sodium-glucose co-transporter 2 (SGLT2) inhibitors, which work by curbing the absorption of glucose via the kidneys so that surplus glucose is excreted through urination. Although the class of drugs is united by similarities, Invokana’s label is crippled with the risk of amputation, unlike Jardiance and Farxiga.
In September, AstraZeneca unveiled data from the DAPA-HF trial, which showed the drug cut the risk of CV death or the worsening of heart failure in patients with heart disease.
The 4,744-patient trial tested Farxiga in patients with reduced ejection fraction (HFrEF) — in which the heart muscle is not able to contract amply and, therefore, expels less oxygen-rich blood into the body — on standard of care treatment, including those with and without type-II diabetes.
Farxiga reduced the composite endpoint of cardiovascular (CV) death or worsening of heart failure by 26% (p<0.0001) — including a reduction in each of the individual components of the endpoint. Data showed there was a 30% decrease (p<0.0001) in the risk of experiencing a first episode of worsening heart failure and an 18% cut (p=0.0294) in the risk of death from cardiovascular causes.
Farxiga, which was approved for use in type-II diabetes back in 2014 — whose sales underwhelmed analyst expectations in the second quarter — is also being evaluated for patients with heart failure in the DELIVER (HFpEF) and DETERMINE (HFrEF and HFpEF) trials, in addition to chronic kidney disease in the DAPA-CKD trial. Its rivals are testing their diabetes offerings in a range of heart and kidney trials as well.
Late last month, the FDA expanded Invokana’s label to slow the progression of diabetic nephropathy (DKD), as well as to reduce the risk of hospitalization for heart failure in patients with type II diabetes and DKD — an indication that no other type II diabetes medicine is approved for.