SGLT-2 inhibitors’ reimbursement expansion to heart failure patients reignites originality debate

The government has decided to expand reimbursement for SGLT-2 inhibitors to patients with chronic heart failure, upending the related market.

However, among many generics with the dapagliflozin ingredient, this coverage included only Dapa.N Tab 10 milligrams, which will likely reignite the controversy over originality that arose when Forxiga withdrew from the domestic market.

The Ministry of Health and Welfare recently said SGLT-2 inhibitors will be covered from February for treating non-diabetic chronic heart failure patients.

Specifically, SGLT-2 inhibitors will be covered for “patients with chronic heart failure with a left ventricular ejection fraction (LVEF) of 40 percent or less who are receiving a stable dose of standard therapy” and for “patients with symptoms and signs of heart failure with an LVEF >40 percent who have left ventricular diastolic dysfunction/increased left ventricular filling pressure (NT-. proBNP ≥125 pg/mL or BNP ≥35 pg/mL) and have objective evidence of cardiac structure or function abnormalities consistent with abnormalities in left ventricular diastolic function/increased left ventricular filling pressure (NT- proBNP ≥125 pg/mL or BNP ≥35 pg/mL) or have an emergency department visit or hospitalization for worsening heart failure within 12 months.

This coverage expansion paves the way for SGLT-2 inhibitors to become the standard of care for people with chronic heart failure but not diabetes, following type 2 diabetes patients.

However, the ministry has specified that the drugs to be covered are Dapa.N Tablet 10 mg (dapagliflozin) and Jardiance Tablet 10 mg (empagliflozin).

This means that the Ministry of Health and Welfare restricted its reimbursement targets to the two drugs currently approved by the Ministry of Food and Drug Safety (MFDS) for the indication of “chronic heart failure.”

From the standpoint of the Health and Welfare Ministry, the decision was made by the MFDS' approval. However, domestic pharmaceutical companies that did not receive the same benefit for their generics are not without something to say.

That’s because the problems raised when Dapa.N took over Forxiga's indication remain unchanged in this benefit expansion.

In late 2023, AstraZeneca Korea abruptly withdrew Forxiga from the Korean market. AstraZeneca was targeting the Chinese market for Forxiga, but the drug's low price in South Korea, the reference country, emerged as an issue.

The Korean government also appeared embarrassed by the unprecedented decision to declare the withdrawal of the original product, which had sold more than 100 billion won ($69.5 million) from the domestic market.

Although there were no risks of dapagliflozin running out of stock because there were generics on the market, patients who were prescribed Forxiga for chronic kidney failure and chronic kidney diseases without diabetes had to change their medication abruptly.

In addition, Forxiga had not completed its post-marketing surveillance (PMS) obligations. So, its withdrawal from the Korean market meant that the regulator faced a situation where it permitted the distribution of generics even before securing the safety of dapagliflozin, the ingredient of their original drug.

In the end, the MFDS allowed HK inno.N to take over Forxiga's cardiac and renal indications to Dapa.N on the condition that the company complete Forxiga's PMS, which was still under patent.

It meant that Dapa.N, which, like other generics, had only demonstrated bioequivalence to Forxiga, could secure the untested heart and kidney indication even without clinical trials.

In the meantime, Forxiga's PMS was completed in 2024. That explains why market insiders predict domestic pharmaceutical companies with dapagliflozin genetics will likely raise equity issues with Dapa.N over this administrative notice.