Experts concerned as AZ's Forxiga withdrawn from Korea amid U.S. pediatric approval

AstraZeneca's SGLT-2 inhibitor Forxiga (dapagliflozin), recently withdrawn from the Korean market, has expanded its indication to treat pediatric type 2 diabetes in the U.S.

This has raised concerns among diabetes experts for Korean patients.

Although HK inno.N, AZ’s Korean partner drugmaker, has transferred Forxiga's existing cardio-renal indication to Dapa.N (dapagliflozin) in exchange for completing Forxiga's post-marketing studies (PMS), it is unclear whether the new indication approved in the U.S. will be available in Korea.

The U.S. FDA approved the use of Forxiga for the control of blood glucose in children 10 years of age and older with type 2 diabetes.

The FDA approval was based on results from the T2NOW phase 3 trial, which evaluated Forxiga as an add-on treatment compared to a placebo in pediatric patients with type 2 diabetes who were already receiving metformin, insulin, or both

Results from the T2NOW study, published in the New England Journal of Medicine (NEJM), showed a significant reduction in glycated hemoglobin (A1C) in the Forxiga treatment group compared to the placebo group. Comparing the change in A1C in the two groups at week 26 of treatment, there was a 0.62 percent decrease in A1C in the Forxiga treatment group compared to a 0.41 percent increase in the placebo group, a difference of 1.03 percentage points.

Announcing the U.S. approval, AstraZeneca said Forxiga is already approved and used to treat adult patients with type 2 diabetes in 126 countries worldwide, including 56 in Europe, and is already available in pediatric patients based on results from another phase 3 study, T2GO.

The company added that additional applications for pediatric indications are planned based on future market assessments.

The news of Forxiga's pediatric indication expansion was met with concern by diabetes experts in Korea.

This concern arises because AstraZeneca Korea withdrew Forxiga from the Korean market following the voluntary cancellation of the drug's regulatory approval on April 25.

AstraZeneca Korea abruptly announced late last year that it was pulling Forxiga from the Korean market. It must have been a difficult decision, given that Forxiga and its lung cancer drug Tagrisso (osimertinib) were the company's revenue-driving duo in the Korean market.

The withdrawal of Forxiga also came as a shock to patients and healthcare providers in the country. Although there are already a number of dapagliflozin-based generics in Korea, the withdrawal of the original drug, which has a patent for its use, comes at a time when new indications are expanding beyond type 2 diabetes to include chronic heart failure and chronic kidney disease.

Korean patients prescribed Forxiga for chronic kidney disease and chronic renal failure without type 2 diabetes were faced with an immediate change in medication.

Furthermore, Forxiga had not completed its PMS obligations. So if it were to withdraw from the domestic market, the regulator, the Ministry of Food and Drug Safety, would allow generics to enter the market without ensuring the safety of the dapagliflozin component.

In the end, the MFDS had no choice but to allow AZ’s local partner HK Inno.N to transfer the heart and kidney indication to Dapa.N in exchange for completing Forxiga's PMS. 

However, the MFDS will face a bigger challenge in the future. Even if the existing Forxiga indications are transferred, there is no way to review new indications approved in other countries.

This is a concern for diabetes experts in Korea. There is a long-awaited drug for pediatric diabetes, which has been lacking treatment options other than metformin and insulin, and there is no way to use it in Korea

Although Korean patients were included in the T2NOW study, which was the basis for the U.S. approval, if the MFDS grants Dapa.N exclusive rights to the pediatric indication, other generic companies are expected to backfire.

Dr. Kim Dae-Jung, an endocrinologist at Ajou University Hospital, posted on Facebook about the U.S. approval of Forxiga and expressed his curiosity about the expansion of indications in Korea. 

He pointed out that with Forxiga's withdrawal from the Korean market, it is unclear who is applying for an expanded indication for pediatric type 2 diabetes.

"Currently, pediatric patients with type 2 diabetes are required to use additional insulin when metformin alone fails to control their blood sugar," said Kim. "Pediatric patients often have severe obesity, and Forxiga may be a better option than insulin for weight loss," he added, emphasizing the need for Forxiga.