Korean Botulinum Toxin Type A Products in Aesthetic Medicine: Regulatory Status, Formulations, and Clinical Evidence

Introduction

Botulinum toxin type A (BoNT-A) is a protein derived from Clostridium botulinum that temporarily reduces muscle activity by blocking acetylcholine release at the neuromuscular junction [1]. It is one of the most widely used agents in aesthetic medicine for the treatment of dynamic facial lines.

South Korean manufacturers have become major contributors to the global BoNT-A market, with several products gaining regulatory approval in the United States and Europe [2]. However, Korean BoNT-A products do not share the same regulatory status across jurisdictions. Some have received U.S. FDA approval; others are approved only in South Korea or selected regional markets.

Terminology note: “Botox®” is a registered trade name (Allergan/AbbVie) and must not be used as a generic term [3]. This article uses “botulinum toxin type A” (BoNT-A) or individual product/INN names throughout.

Regulatory Framework

In the United States, BoNT-A products are regulated as biologics by the FDA, requiring demonstration of safety and efficacy through clinical trials [4]. In South Korea, the Ministry of Food and Drug Safety (MFDS) regulates these products under the Pharmaceutical Affairs Act [5]. MFDS approval alone does not confer FDA or EMA approval; separate applications are required for each jurisdiction.

Table 1. Regulatory status of Korean-origin BoNT-A products as of mid-2024 (Sources: FDA Purple Book [4]; MFDS Korea [5]).

Product Profiles

Nabota / Jeuveau® (prabotulinumtoxinA)

Manufacturer: Daewoong Pharmaceuticals; distributed in the U.S. by Evolus Inc [6].
FDA approval: 18 February 2019 for moderate-to-severe glabellar lines in adults [7].
Clinical evidence: Two Phase III randomised, double-blind, placebo-controlled trials (EV-001 and EV-002; n=675) showed statistically significant improvement versus placebo at Day 30 (p < 0.001), sustained over repeat cycles [8]. A comparative study (BLOSSOM) demonstrated non-inferiority to onabotulinumtoxinA [9].
Formulation: Lyophilised powder, 900 kDa complex, excipients: human albumin and sodium chloride [10].
Immunogenicity: Neutralising antibodies not detected in trial subjects; long-term post-market surveillance ongoing [10].

Botulax / Letybo® (letibotulinumtoxinA)

Manufacturer: Hugel Inc.; distributed in the U.S. by Hugel America Inc.[11].
FDA approval: 21 February 2024 (seventh BoNT-A product approved in the U.S. for aesthetic use) [12].
Clinical evidence: BLESS Phase III programme showed onset within 2–3 days, peak effect at Day 14, and duration approximately 3–4 months. An active-controlled study demonstrated non-inferiority to onabotulinumtoxinA [13].
Formulation: Lyophilised powder, 900 kDa complex.
Immunogenicity: Neutralising antibody formation was rare in clinical trials; post-marketing surveillance is ongoing per EMA assessment report [14].

Innotox

U.S. status: NOT FDA-approved. The FDA has issued warnings against the use of unapproved BoNT-A products. U.S. clinicians and patients should use only FDA-approved products.
Manufacturer: Medytox Inc. Approved by MFDS Korea and in selected other markets.
Formulation: Ready-to-use liquid (no reconstitution required); 150 kDa core; no human serum albumin (HSA); requires refrigeration at 2–8°C [15].
Clinical evidence: Published studies are predominantly from Asian markets; Phase III data in Western populations meeting FDA/EMA standards are not available in the published literature [16].
Immunogenicity: The absence of complexing proteins and HSA theoretically reduces the immunogenic stimulus; direct comparative data remain limited [17].

Coretox

U.S. status: NOT FDA-approved or EMA-approved.
Manufacturer: Medytox Inc. Approved in South Korea and selected markets.
Formulation: Lyophilised powder containing only the 150 kDa neurotoxin core, without accessory (complexing) proteins, analogous to incobotulinumtoxinA (Xeomin®, FDA-approved 2011) [18].
Immunogenicity rationale: Complexing proteins are thought to act as antigens contributing to neutralising antibody formation over repeated treatments. Protein-free formulations may reduce this risk, as indicated by studies of incobotulinumtoxinA [18,19]. Independent comparative data for Coretox are not yet available.

Liztox

U.S. status: NOT FDA-approved.
Manufacturer: Huons Co., Ltd. Approved by MFDS Korea [20].
Formulation: Lyophilised powder, 900 kDa complex. Published analytical data report high purity by SDS-PAGE; however, direct cross-product comparisons are unreliable without a standardised assay methodology applied uniformly across manufacturers [21].
Clinical evidence: Available studies address glabellar lines, with outcomes broadly consistent with the class; Phase III data in Western populations that meet FDA/EMA standards have not been identified in the published literature.

Comparative Overview

Table 2. Key formulation characteristics.

Efficacy: Head-to-head trials across Korean products are limited. Jeuveau® and Letybo® both demonstrated non-inferiority to onabotulinumtoxinA in glabellar line treatment [8,13]. BoNT-A units are not interchangeable across manufacturers; dosing must follow the prescribing information for each product.

Safety: Adverse event profiles for FDA-approved Korean products are consistent with the BoNT-A class: injection-site reactions, headache, and infrequent eyelid ptosis [10,12].

Immunogenicity: Repeated BoNT-A treatment carries a risk of neutralising antibody development. Complexing protein-free formulations theoretically reduce this risk; long-term comparative data across Korean products are not yet available [17-19].

Cost: Korean-origin products have generally entered markets at lower price points than some established Western brands, reflecting manufacturing economics. Clinical decisions must not be driven by cost when regulatory approval and established safety data are relevant factors.

Safety Guidance for Clinicians

• Use only products with current regulatory approval in your jurisdiction (in the U.S., FDA-approved products only).
• Procure BoNT-A products exclusively from licensed, verified distributors. Unregulated online channels carry significant legal and patient safety risks [22]. In the U.S. market, Korean BoNT-A products are available through authorised wholesale distributors such as Filler Cloud.
• BoNT-A units are manufacturer-specific and not interchangeable [10].
• Assess carefully patients with known hypersensitivity to formulation components or neuromuscular junction disorders [10,12].
• Informed consent should specify the product, its regulatory status, and expected benefits and risks.

Conclusion

Two Korean-origin BoNT-A products have achieved FDA approval and are supported by rigorous Phase III evidence: prabotulinumtoxinA (Jeuveau®, 2019) and letibotulinumtoxinA (Letybo®, 2024), both for moderate-to-severe glabellar lines in adults. Innotox, Coretox, and Liztox do not currently hold FDA or EMA approval; their use in the United States or European Union is not consistent with applicable regulatory frameworks.

Product selection should be based on regulatory approval status, available clinical evidence, individual patient factors, and compliance with local regulations. Further research through standardised, adequately powered clinical trials is needed to establish comparative long-term efficacy, safety, and immunogenicity profiles across Korean and other BoNT-A formulations.

References

1. Carruthers A, Carruthers J. History of the cosmetic use of Botulinum A exotoxin. Dermatol Surg. 1998 Nov;24(11):1168-70. doi: 10.1111/j.1524-4725.1998.tb04092.x.
2. Rho NK, Han KH, Kim HS. An update on the cosmetic use of Botulinum toxin: the pattern of practice among Korean dermatologists. Toxins (Basel). 2022 May 4;14(5):329. doi: 10.3390/toxins14050329.
3. Allergan Aesthetics (AbbVie). Botox® Cosmetic Prescribing Information. North Chicago, IL: AbbVie Inc.; 2023.
4. U.S. Food and Drug Administration. Guidance for Industry: Biologics License Applications. Available at: www.fda.gov.
5. Ministry of Food and Drug Safety (MFDS), Republic of Korea. Pharmaceutical Affairs Act Guidelines. [Accessed 2024].
6. Evolus Inc. Annual Report 2023. Santa Barbara, CA: Evolus Inc.; 2023.
7. U.S. FDA. FDA approves Jeuveau (prabotulinumtoxinA-xvfs). FDA Press Release. 18 February 2019. Available at: www.fda.gov.
8. Beer KR, Shamban AT, Avelar RL, Gross JE, Jonker A. Efficacy and safety of prabotulinumtoxinA for the treatment of glabellar lines in adult subjects: results from 2 identical phase III studies. Dermatol Surg. 2019 Nov;45(11):1381-1393. doi: 10.1097/DSS.0000000000001903.
9. Solish N, Ascher B, Avelar RL, et al. PrabotulinumtoxinA vs onabotulinumtoxinA for the treatment of adult males with moderate to severe glabellar lines: post-hoc analyses of the phase III clinical study data. Aesthet Surg J. 2022 Dec 14;42(12):1460-1469. doi: 10.1093/asj/sjac210.
10. Evolus Inc. Jeuveau® Prescribing Information. Santa Barbara, CA: Evolus Inc.; 2023.
11. Hugel Inc. Corporate Information. Available at: www.hugel.co.kr [Accessed 2024].
12. U.S. FDA. FDA approves Letybo (letibotulinumtoxinA-wlbg). FDA Press Release. 21 February 2024. Available at: www.fda.gov
13. Gold M, Taylor S, Mueller DS, et al. Efficacy and safety of letibotulinumtoxinA in the treatment of moderate and severe glabellar lines in females 35 to 50 years of age: post hoc analyses of the phase 3 clinical study data. Aesthet Surg J Open Forum. 2024 Feb 23;6:ojae010. doi: 10.1093/asjof/ojae010.
14. European Medicines Agency. Letybo: European Public Assessment Report. Amsterdam: EMA; 2023.
15. Samizadeh S, De Boulle K. Botulinum neurotoxin formulations: overcoming the confusion. Clin Cosmet Investig Dermatol. 2018 May 30;11:273-287. doi: 10.2147/CCID.S156851.
16. Carruthers JA, Lowe NJ, Menter MA, et al. BOTOX Glabellar Lines I Study Group. A multicenter, double-blind, randomized, placebo-controlled study of the efficacy and safety of botulinum toxin type A in the treatment of glabellar lines. J Am Acad Dermatol. 2002 Jun;46(6):840-9. doi: 10.1067/mjd.2002.121356.
17. Dressler D. Clinical presentation and management of antibody-induced failure of botulinum toxin therapy. Mov Disord. 2004 Mar;19 Suppl 8:S92-S100. doi: 10.1002/mds.20022.
18. Martin MU, Frevert J, Tay CM. Complexing protein-free Botulinum Neurotoxin A formulations: implications of excipients for immunogenicity. Toxins (Basel). 2024 Feb 10;16(2):101. doi: 10.3390/toxins16020101.
19. Frevert J. Xeomin is free from complexing proteins. Toxicon. 2009 Oct;54(5):697-701. doi: 10.1016/j.toxicon.2009.03.010.
20. Huons Co. Ltd. Liztox product information. MFDS registration data. [Accessed 2024].
21. Hong JY, Kim JH, Jin JE, Shin SH, Park KY. Practical Application of Novel Test Methods to Evaluate the Potency of Botulinum Toxin: A Comparison Analysis among Widely Used Products in Korea. Toxins (Basel). 2021 Nov 23;13(12):833. doi: 10.3390/toxins13120833. PMID: 34941671; PMCID: PMC8707463.
22. U.S. FDA. FDA warns about risk of purchasing unapproved botulinum toxin. FDA Safety Communication. 2023. Available at: www.fda.gov

Disclaimer: This article is for informational purposes only and does not constitute medical, legal, or regulatory advice. Regulatory status, indications, and safety information may vary by jurisdiction and change over time. Healthcare professionals should consult current prescribing information, local regulations, and appropriate regulatory authorities before using or recommending any botulinum toxin product. Open MedScience does not endorse any specific product, manufacturer, or distributor and accepts no liability for decisions made based on this content.

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