[Edaily Reporter NA EUN-KYUNG ] CORESTEMCHEMON(166480)CoaStem ChemOn has finalized the direction for the follow-up clinical development in the U.S. of its Lou Gehrig’s disease treatment, “NeuronaTa-R.” Although the company failed to meet the primary endpoint in a previous Phase 3 clinical trial, the U.S. Food and Drug Administration (FDA) has indicated that the approach of validating the efficacy signals observed in the existing clinical trial through a new trial is reasonable.

CORESTEMCHEMON announced on the 19th that it had discussed the follow-up development strategy for its amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease) stem cell therapy “NeuronaTa-R Injection” (active ingredient: 렌주메스트로셀) with the FDA on the 17th (Korean time).

This consultation took place during a Type C meeting, which is the FDA’s official development consultation procedure. A Type C meeting is a process through which a pharmaceutical company seeks the FDA’s opinion on the interpretation of existing clinical results or the design of follow-up trials. This discussion is significant in that it confirmed the direction for continued development of Neuronata-R—which failed to achieve statistical significance in its Phase 3 clinical trial—based on existing data.

The company presented the FDA with efficacy and safety results from Phase 2 and 3 clinical trials, biomarker analyses, long-term follow-up data, and post-marketing surveillance data from South Korea. The FDA expressed the view that it would be reasonable to validate the signals of efficacy observed in the existing clinical trials and long-term follow-up studies through new clinical trials.

CORESTEMCHEMON cited initial differences in lung function between the treatment and control groups as a potential factor that may have influenced the Phase 3 results. At that time, the median forced vital capacity (FVC) in the treatment group was 65–74.5%, which was lower than the control group’s 81%. In contrast, in the Phase 2 trial, lung function in both groups was similar at approximately 74%, and a statistically significant difference in functional scores was observed at the 6-month mark.

For the subsequent Phase 3b clinical trial, a plan was discussed to compare the treatment with a placebo for 24 weeks after administration, followed by treatment for both groups until week 48. The primary endpoint is proposed to be the change in the ALSFRS-R score at 24 weeks, which assesses patients’ daily functions such as speaking, swallowing, walking, and breathing. In accordance with FDA recommendations, mortality is being considered for separate evaluation as a key secondary endpoint.

A proposal was made to use blood levels of neurofilament light chain (NfL)—which indicates the extent of nerve damage—for patient screening. The company confirmed that the disease tends to progress rapidly in patients with NfL levels exceeding 75 pg/mL. While the FDA deemed this approach reasonable, it requested that the company supplement the screening criteria and the rationale for using blood tests based on its own Phase 2 clinical trial data.

Regarding safety, the company explained that the FDA raised no significant concerns regarding the data, which included 388 patients from a post-marketing surveillance study in South Korea.

Reflecting these discussions, CORESTEMCHEMON plans to finalize its Phase 3b clinical trial protocol and hold further discussions with the FDA regarding additional requirements related to manufacturing and quality control (CMC). While the company is reviewing the possibility of follow-up clinical trials and accelerated approval in the U.S., the accelerated approval pathway has not yet been finalized.

NeuronaTa-R is a therapy that uses mesenchymal stem cells harvested from the patient’s own bone marrow and received conditional approval in South Korea in 2014.

A CORESTEMCHEMON official stated, “The fact that the FDA has designated not only Phase 3 but also Phase 2 data as the basis for the subsequent clinical trial design confirms the value of the clinical results we have accumulated so far,” adding, “Now that the direction has been set, the key will be how thoroughly we prepare the data requested by the FDA.”