[Good Brain 2026] "GLP-1 CNS Drugs Must Prove BBB Penetration and Safety Margin"

Evidence Required for New Indications: Mechanism of Action and Data from Disease Animal Models
High-Dose or Long-Term Use Requires Repeat Toxicity Studies and Safety Margin Assessment Against Clinical Use

It has been pointed out that, to expand the use of glucagon-like peptide-1 (GLP-1) class drugs from the treatment of obesity and diabetes to central nervous system (CNS) disorders such as dementia and Parkinson's disease, more robust data are needed regarding not only the mechanisms of action and efficacy for new indications but also whether the drugs actually reach the brain. It was also suggested that the "safety margin," which involves comparing the safety levels obtained from nonclinical studies with the dosage used in clinical trials, must be carefully scrutinized.

Sohee Kim, Director of the Circulatory Nervous System Drug Division at the Ministry of Food and Drug Safety, is giving a lecture at the "2026 Good Brain Conference" hosted by The Asia Business Daily on the 3rd at the Western Chosun Hotel Seoul in Jung-gu, Seoul. Photo by Hyunmin Kim

Sohee Kim, Director of the Circulatory Nervous System Drug Division at the Ministry of Food and Drug Safety, explained these points during her lecture on “The Role of Policy in the Era of GLP-1-Based Innovative Drugs” at the “2026 Good Brain Conference,” held on September 3, 2026, at the Westin Chosun Hotel Seoul in Jung-gu, Seoul, hosted by The Asia Business Daily under the theme of “Brain Revolution: How GLP-1 Will Change the Future of Humanity.”

Director Kim emphasized that the application of GLP-1 to CNS indications should be regarded as the development of "new indications." Therefore, it is essential to distinguish between the data that can be leveraged from the treatment processes for obesity and diabetes and the data that must be newly obtained. If the new indications fall within the CNS field, such as dementia or alcohol use disorder, data supporting the underlying mechanism of action and efficacy studies using animal models representative of the targeted disease are required.

In the case of developing new drugs as CNS therapeutics, whether the drug can cross the blood-brain barrier (BBB) is an especially critical consideration. Director Kim remarked, "It is necessary to investigate whether the drug exerts its effect by crossing the BBB or by some other mechanism," adding, "If the drug does cross the BBB, then factors such as the degree of crossing and the extent to which it is distributed in the brain, as well as the evidence supporting efficacy for CNS indications, all become subjects for review."

If the administered dose is higher than those used for obesity or diabetes treatment, additional toxicity data may be required. Specifically, it is crucial to assess the safety margin by comparing the clinical dose to the no-observed-adverse-effect-level (NOAEL) identified in nonclinical studies. Director Kim explained, "If earlier toxicology studies only demonstrated a 0.5-fold margin, but now, for a clinical trial, the planned dose is increased to about twice the previous amount, the Ministry of Food and Drug Safety would inevitably have concerns," emphasizing the need to secure a sufficient safety margin between the high doses intended for clinical use and the safety levels confirmed in nonclinical studies.

For CNS drugs intended for long-term administration, it is also necessary to obtain repeat-dose toxicity data corresponding to the actual period of use. The required duration of toxicity testing varies depending on the clinical development stage and the anticipated administration period, and if long-term treatment is expected, appropriate nonclinical safety data will be necessary.

Director Kim advised, "Companies preparing to develop new CNS indications for GLP-1 should consult with the Ministry of Food and Drug Safety early in the development process to determine the required data." Through its pre-consultation service for innovative products, the Ministry provides consultations on research, nonclinical, and clinical development strategies and trial design before clinical trials begin, as well as offering safety and efficacy checklists (60 general items and 10 items specific to biologics) and a risk management plan (RMP) checklist reflecting frequently requested supplementations, enabling companies to self-assess their readiness.

Director Kim added, "Since this year, the Ministry of Food and Drug Safety has also launched a project to develop guidelines for accelerated drug development, including considerations for drug development using artificial intelligence (AI) and guidelines for developing therapeutics for Parkinson's disease." She continued, "Guidelines for nonclinical and clinical fields are continually being prepared for companies developing medicines based on new technologies or new concepts."

Sohee Kim, Director of the Neurocirculatory Drugs Division at the Ministry of Food and Drug Safety, is giving a lecture on the 3rd at the Western Chosun Hotel Seoul in Jung-gu, Seoul, hosted by The Asia Business Daily at the '2026 Good Brain Conference'. Photo by Hyunmin Kim

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