韩国胆碱制剂临床再评价失败与医保追缴风险已被系统近72小时内处理

Health authorities have recently accelerated follow-up procedures surrounding choline preparations because pharmaceutical companies submitted the results of a clinical reassessment for the mild cognitive impairment indication last month. As the submitted clinical results failed to meet the primary endpoint, the outlook for whether the indication will be maintained and the scale of the health insurance reimbursement clawback is expected to take shape soon.
According to the pharmaceutical and biotech industry on the 26th, a clinical reassessment is a procedure to re-verify the efficacy of an already-approved and marketed drug through clinical trials. This is the first large-scale confirmatory clinical trial conducted on choline preparations in Korea. When choline preparations received domestic approval in 2000, the "foreign pharmacopoeia-based system" applied, under which an ingredient listed in a pharmacopoeia of an advanced country could receive indication approval and health insurance coverage without a separate clinical trial.
The controversy surrounding choline preparations was set off in earnest when a public interest audit — arguing that "more than 1 trillion won in health insurance funds is being spent on a drug without evidence" — was filed with the Board of Audit and Inspection in 2019. Among the eight countries Korea references for its drug pricing policy (A8: the U.S., U.K., Germany, France, Italy, Switzerland, Japan and Canada), seven excluding Italy treat choline preparations as food ingredients or health functional foods, and even Italy, which developed choline preparations, classifies them as drugs but does not apply health insurance coverage.
Accordingly, the Ministry of Health and Welfare in 2020, 20 years after their introduction, decided to reduce reimbursement (converting to selective reimbursement) for some indications including mild cognitive impairment. Furthermore, the Ministry of Food and Drug Safety required pharmaceutical companies to prove efficacy through a clinical reassessment and stated it would delete the indications if they failed to do so. The National Health Insurance Service (NHIS) also signed conditional clawback contracts with the pharmaceutical companies to recover 20% of prescription amounts paid from the date of clinical trial plan approval to the point of deletion, in the event the indications are deleted.
Currently, the only thing pharmaceutical companies can rely on is the formal clinical reassessment result. This is because they have suffered successive losses in the lawsuit to cancel the reimbursement reduction, the lawsuit to cancel the clawback negotiation order, and the lawsuit to nullify the clawback negotiation contract, filed against the government. Earlier, the pharmaceutical companies filed a lawsuit to cancel the reimbursement reduction, a lawsuit to cancel the clawback negotiation order, and a lawsuit to nullify the clawback negotiation contract against the government, but lost them one after another. The Supreme Court ultimately ruled in favor of the government in the clawback negotiation order cancellation lawsuit and the reimbursement reduction cancellation lawsuit in 2024 and 2025, respectively. The clawback negotiation contract nullification lawsuit lost at the first trial at the Seoul Administrative Court last year and is currently in the appellate stage.
The government had originally planned to reduce reimbursement at the same time as its announcement and to complete the clinical reassessment by 2025. However, as the lawsuits surrounding choline preparations continued for five years and the clinical trials were delayed due to COVID-19, the reimbursement reduction was carried out last year, and the final results of the mild cognitive impairment clinical trial were submitted only last month.
The problem is that the choline preparation clinical trial for mild cognitive impairment (degenerative and vascular) conducted by pharmaceutical companies failed to achieve the primary endpoint. There was no significant difference in the maintenance or improvement of cognitive function between the group that took choline preparations and the patient group that did not. In a supplementary analysis targeting a patient group that faithfully followed certain medication standards (PPS), a difference of 7.76 percentage points was found, but there is a problem that PPS may be biased toward patient groups that manage their health well due to its nature, so it is uncertain whether the Ministry of Food and Drug Safety will accept it. A Ministry of Food and Drug Safety official said, "As the reassessment result report has been submitted, we plan to review it based on scientific validity." The clinical trial for the Alzheimer's-type dementia indication is scheduled to submit results in December next year.
If the Ministry of Food and Drug Safety ultimately decides to delete the indication, the NHIS will begin a large-scale clawback procedure. According to pharmaceutical market research firm UBIST, choline preparation prescription amounts were 622.3 billion won in 2023, 612.3 billion won in 2024, and 545.6 billion won in 2025, maintaining an annual market of 500 billion to 600 billion won until recently. Applying a simple 20% to prescription amounts from June 2021, when the clinical trials began, to the present, the clawback scale exceeds 500 billion won. An official from the Pharmacists for Democratic Society, which filed the public interest audit, argued, "In the case of choline preparations, the possibility of side effects such as stroke and cerebral hemorrhage from long-term use has been raised, so maintaining the indication is not the only answer."
Reflecting this situation, pharmaceutical companies selling choline preparations are reflecting clawback contingent liabilities in their accounting. Estimated liabilities reflected by Daewoong Bio and Chong Kun Dang, which have the largest prescription volumes, assuming failure of the clinical reassessment, each approach 100 billion won. Hanmi Pharmaceutical, Alico Pharmaceutical, Dongkoo Bio & Pharma, Kukje Pharma, Dongkwang Pharmaceutical, Genuone Pharma, Dongkook Pharmaceutical and Whanin Pharmaceutical are also reflecting potential clawback amounts ranging from tens of billions to hundreds of billions of won in their financial statements.