FDA Approves Farxiga to Improve Glycemic Control in Pediatric Patients with Type 2 Diabetes

The FDA has approved AstraZeneca’s Farxiga (dapagliflozin) to improve glycemic control in patients 10 years of age and older with type 2 diabetes (T2D). Farxiga is a sodium-glucose cotransporter 2 inhibitor previously FDA-approved as an adjunct to diet and exercise to improve glycemic control in adults with T2D mellitus.¹

“The prevalence of [T2D] continues to rise in children and adolescents, yet oral treatment options have remained limited for this population,” said Ruud Dobber, executive vice president, BioPharmaceuticals Business Unit, AstraZeneca, in a press release.” [The] approval represents an important milestone for pediatric patients living with [T2D] in the US, extending this medicine’s potential benefits to even more patients facing high unmet needs and reinforcing AstraZeneca’s commitment to delivering innovative treatments across cardiovascular, renal and metabolic diseases.”¹

In addition to the indications in diabetes, Farxiga has also been approved by the FDA to lower the risk of hospitalization for heart failure (HF) in adults with T2D mellitus and either established cardiovascular disease (CVD) or multiple CVD risk factors; to decrease the risk of CVD death and hospitalization for HF in adults with reduced ejection fraction; to lower the risk of sustained estimated glomerular filtration rate decline, end-state kidney disease, cardiovascular death, and hospitalization for HF in adults with chronic kidney disease at risk of progression.²

The latest approval was based on data from the randomized, double-blind, placebo-controlled, pediatric T2NOW Phase III trial (NCT03199053). The trial analyzed the effectiveness and safety of Farxiga as add-on treatment in pediatric patients with T2D administered metformin, insulin, or both. Investigators randomly assigned participants to receive dapagliflozin, saxagliptin, or placebo.

Patients currently treated with an active drug were further randomly assigned to continue with their current dose or increase to a higher dose of the same active treatment. The trial’s primary endpoint was change in A1C following 26 weeks compared with placebo for Farxiga (5 or 10 mg) or saxagliptin (2.5 or 5 mg), with secondary endpoints that included change in fasting plasma glucose and proportion of patients (A1C ≥7% at baseline) reaching A1C <7.0% (53 mmol/mol).

The results showed a significant decrease in A1C among patients administered Farxiga compared with those administered placebo, at -0.62% in the Farxiga cohort compared with +0.41% with placebo, which translates to a difference of -1.03% (95% CI: -1.57-0.49; p<0.001).^1,3 In terms of safety, adverse events (AEs) and serious AEs were reported by 72.8% and 8.6% of patients administered Farxiga, respectively, 69.3% and 8.0% of patients administered saxagliptin, respectively, and 71.1% and 6.6% of patients administered placebo, respectively.

Severe hypoglycemia was observed in 4.9%, 4.5%, and 7.9% of patients in each group, respectively. The most frequently reported AE during the 52-week trial was headache, with most AEs deemed mild and none considered serious or leading to treatment discontinuation.³

“[Farxiga], but not saxagliptin, showed significant improvement in A1C compared with placebo. Nonserious headaches were more common in participants treated with dapagliflozin than in those receiving placebo,” the investigators wrote of the results in a study published in The New England Journal of Medicine.³

In a press release, AstraZeneca stated that it will evaluate additional regulatory submissions and rollout plans pending further market evaluations.

References

1. AstraZeneca. June 12, 2024. Accessed June 12, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/farxiga-approved-in-the-us-for-the-treatment-of-paediatric-type-2-diabetes.html#

2. Schechter M, Jongs N, Chertow GM, et al. Effects of dapagliflozin on hospitalizations in patients with chronic kidney disease: a post hoc analysis of DAPA-CKD. Ann Intern Med. Published December 6, 2022. doi:10.7326/m22-2115.

3. Shehadeh N, et al. Dapagliflozin or Saxagliptin in Pediatric Type 2 Diabetes. NEJM Evid 2023;2(12). DOI: 10.1056/EVIDoa2300210. https://evidence.nejm.org/doi/abs/10.1056/EVIDoa2300210