According to the pharmaceutical and biotech industry on the 18th, 130 NATURECELL CO.,LTD. shareholders recently refiled a complaint with the Seoul Metropolitan Police Agency against MFDS Commissioner Oh Yu-kyung, relevant officials, and members of the Central Pharmaceutical Affairs Deliberation Committee, accusing them of dereliction of duty, abuse of authority, and obstruction of the exercise of rights.
Previously, in 2023, 263 shareholders of NATURECELL CO.,LTD. had filed a complaint with the prosecution against MFDS officials and committee members, alleging dereliction of duty and obstruction of business during the review process for JointStem’s marketing authorization. However, the prosecution decided not to indict them in October of that year, ruling there was insufficient evidence. At the time, the prosecution reportedly cited, among other reasons, the fact that it was difficult to conclude that Albio (now R&L Regenerative Medicine Research Institute)—an affiliate of NATURECELL CO.,LTD. and the developer of JointStem—possessed a specific right to obtain marketing authorization.
R&L Regenerative Medicine Research Institute—which changed its name from Albio—subsequently submitted supplementary data and reapplied for marketing authorization, but filed an administrative lawsuit after the application was rejected again in August of last year. Following the Seoul Administrative Court’s ruling last month to overturn the MFDS’s rejection, the shareholders used this as new evidence to file a fresh complaint.
The court held that since statistical significance was confirmed in the Phase 3 clinical trial for Jointstem, it would be difficult to conclude that it lacks clinical significance. Furthermore, the court determined that the MFDS’s requirement that Jointstem demonstrate superior efficacy compared to already approved treatments constituted the addition of a criterion without legal basis.
Attorney Yoon Yong-jin, who represented the plaintiffs in the re-filed complaint, stated, “The court clearly ruled that if statistical significance is recognized, clinical significance must also be recognized, and that there is no legal basis for requiring superiority over other treatments,” adding, “This effectively means that approval cannot be denied based on the reasons presented so far.”
Efficacy Cannot Be Determined by p-Value Alone… The Key Is the Scope of Regulatory DiscretionOf course, the act
ofa regulatory agency
reviewinga drug’s efficacy or clinical significance is not, in itself, illegal or unusual.
Statistical significance means that the difference between the treatment group and the control group in a clinical trial is unlikely to have occurred by chance. Generally, if the p-value—the standard for determining statistical significance—is less than 0.05, it is considered to have “achieved statistical significance.” However, with a large number of patients, even a small effect can appear statistically significant; therefore, a separate assessment is needed to determine whether the drug’s efficacy is actually noticeable to patients.
In fact, the U.S. Food and Drug Administration (FDA) specifies in its official guidelines, based on the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH), that to demonstrate the efficacy of a drug, the effect size, confidence interval, and p-value from individual clinical trials must be presented together; presenting only the p-value is not sufficient. It also requires that the clinical significance of the outcome measure and the actual observed effect size be evaluated separately. The Ministry of Food and Drug Safety (MFDS), an ICH member, has also incorporated these same regulatory principles into domestic regulations.
There have also been cases where different regulatory agencies reached differing conclusions based on the same clinical data. This was the result of a comprehensive assessment that took into account the effect size, reproducibility, and safety, even when statistical significance was confirmed.
Biogen’s Alzheimer’s disease treatment “Aduhelm” (active ingredient: aducanumab) achieved statistical significance in one of its two Phase 3 clinical trials, with a p-value of 0.012. However, the European Medicines Agency (EMA) determined that the clinical significance was uncertain, as the difference from the placebo group on the Clinical Dementia Rating Scale-Short Form (CDR-SB)—which assesses cognitive and functional decline—was only 0.39 points (the threshold set was 0.5 points). Taking safety risks into account as well, the EMA ultimately reached a negative conclusion regarding approval. In contrast, the FDA granted accelerated approval to Aduhelm, concluding that the surrogate endpoint—a reduction in amyloid-beta plaques in the brain—had the potential to predict future clinical benefit.
Consequently, some analysts suggest that the MFDS’s review of whether the effect size of Jointstem is meaningful to patients cannot be viewed as deviating from international review practices. A biotech industry official stated, “The MFDS will likely assess whether the drug demonstrates clinical significance and meets the standard of being superior to existing treatments,” adding, “In the future, the scope of discretion allowed to regulatory agencies is likely to become a major point of contention.”
The issue raised by the Administrative Court in this case also concerns the criteria for comparison with existing treatments. The court pointed out that if a product is required to demonstrate superior efficacy compared to existing treatments to receive marketing authorization, this would result in the protection of existing drugs and restrict the market entry of new drugs. The court’s reasoning is that, as this restricts free competition and the freedom to develop and market new drugs, a clear legal basis is necessary.
Conflict of Interest Among Review Committee Members Also a Point of Controversy The issue of potential conflicts of interest among review committee membershas resurfaced. The court ruling determined that an individual who actively presented a negative opinion during the first Central Drug Review Committee meeting was in a potential competitive relationship with Albio in the field of stem cell therapy development. Shareholders identify this individual as Professor Oh Il-hwan of the Catholic University of Korea College of Medicine, who served as the chair of the Central Drug Review Committee at the time.
The shareholders argue that since Professor Oh, who founded a stem cell-related company, participated in the JointStem review, there was a potential conflict of interest, and that the Ministry of Food and Drug Safety (MFDS) should have verified this and excluded him from the review. They also cited the court’s remark that it appeared the committee member in question had intended to block the product’s market launch as grounds for refiling the complaint.
However, Professor Oh refuted the claim that RegeneInnoPharm, the company he founded, is a stem cell therapy firm competing with JointStem, stating that it is not true. Professor Oh stated, “Regen InnoPharm is not a company that administers stem cells directly; rather, it develops therapies that activate the body’s regenerative functions using synthetic substances such as peptides and ribonucleic acid (RNA),” adding, “We have never conducted research on arthritis or developed treatments for it.”
In fact, Regene Inopharm’s publicly disclosed pipeline contains no candidates for the treatment of osteoarthritis or cell therapies. Its main pipeline includes: △PU001 (indication: diabetic foot ulcers) △RH001 (acute myocardial infarction) △PN001 (cerebral infarction) △PN002 (Alzheimer’s disease) △RR001(retinal disease), and △PV001 (vascular disease). Rather than administering stem cells directly, the approach involves using molecular substances such as RNA and peptides to activate the patient’s own stem cells and regenerative functions.
Based solely on product types and indications, it is difficult to categorically label Regene InnoPharm as a direct competitor of Jointstem. However, in that both companies aim to regenerate damaged tissue, they both fall within the field of regenerative medicine in a broad sense. The key issue is whether to narrowly assess potential conflicts of interest based on shared indications and the development of similar products, or to take a broader view that includes business and academic interests within the regenerative medicine sector.
Some argue that the related allegations were already resolved in 2023 when the prosecution decided not to indict. However, the shareholders contend that new evidence has emerged, given that the Administrative Court explicitly addressed the MFDS review process and competition issues in its ruling.
Attorney Yoon stated, “If there had been no new ruling, it would have been pointless to file another complaint based on the same grounds,” adding, “Since the Administrative Court specifically pointed out in its ruling the aspects that the previous investigation had deemed unproblematic, we viewed this as new circumstances and evidence and filed a renewed complaint.”
