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ALS Cell Therapy Receives US Patent

AstroRx previously demonstrated clinically meaningful reductions in the rate of disease progression.

Israeli cell therapy company Kadimastem has been granted a patent from the United States Patent and Trademark Office for AstroRx, a cell therapy consisting of astrocytes derived from human embryonic stem cells intended for the treatment of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS).1

“The ALS program is progressing well," Michel Revel, MD, PhD, founder and chief scientist, Kadimastem, said in a statement regarding the news. "The company’s broad patent portfolio was strengthened today, and we are on track to begin the much anticipated clinical trial of AstroRx within months. I am excited to see our original vision come to fruition. The goal is to improve the treatment of ALS patients.”

Kadimastem previously announced positive results from cohort B of its phase 1/2a clinical trial of AstroRx (NCT03482050) in late 2020. During the 6 month post-treatment follow-up of the 5 patients dosed in the higher-dose cohort (Cohort B), there were no treatment-related serious adverse events nor dose limiting toxicities reported.2

"The results after 6 months of follow up are encouraging, as they suggest a clinically meaningful signal of effect for a period of 3 months by a single administration of AstroRx and confirm the safety of AstroRx,” Marc Gotkine, head of the ALS Clinic at the Department of Neurology at Hadassah Medical Center, Jerusalem, and principal investigator of the trial, said in a statement at the time.2 “These results support a further, randomized-controlled, clinical trial with repeated doses of AstroRx in patients with ALS, in order to prolong the clinical effect observed by a single dose.”

AstroRx was shown to provide a clinically meaningful reduction in the rate of disease progression measured on the ALS Functional Rating Scale-Revised (ALSFRS-R), from -1.43/month in the 3 to 4 months prior to treatment to -0.78/month during the 3-4 months after treatment. However, this 45% decline (P = .0023) in disease progression rate did not persist, and by the end of the 6-month period ALSFRS-R progression had returned to a rate similar to pre-treatment rates, indicating that continuous doses might be needed for sustained efficacy. Data from 5 patients in the lower dose cohort (Cohort A), reported earlier in 2020, displayed similar results in terms of efficacy and safety.

“The 6-month follow up data demonstrates the safety of AstroRx as a treatment for ALS,” Revel added to the statement.2 “The results also support the strategy of a repeated administration of the AstroRx cells using the intrathecal route. As such, we are planning to continue with this strategy during the next phase of the clinical development program.”

As of January 2021, the open-label, dose-escalation trial had recruited 16 participants between the ages of 18 and 70 years who had been diagnosed with probable or definite ALS. Participants were required to have an ALS-FRS-R score of at least 30 and an ALS diagnosis of 2 years or less, and patients being treated with Riluzole and/or Radicava were required to have been on a stable dose with these medications for at least 30 days. Patients who had past infections with or a positive test for HBV, HCV, or HIV were excluded from the study, as were patients in need of respiratory support, and those who scored lower than 10/12 in the ALSFRS-R respiratory parameters or below 70% of predicted slow vital capacity (SVC).

AstroRx was administered via intrathecal injection. Patients in cohort A were treated with a dose of 100x106 AstroRx cells and patients in cohort B received a dose of 250x106 AstroRx cells. The primary end point is the number of participants who experienced treatment emergent adverse events. Secondary end points include the change in the ALS functional rating scale, change in predicted SVC, changes in muscle strength grading measured by JAMAR grip strength and handheld dynamometer, and the change in the ALSAQ-40 quality of life questionnaire.

Kadimastem has announced their intention to submit an investigational new drug application by the end of 2022 and is currently preparing for the start of the phase 2a study in the US in 2023.1

REFERENCES
1. Kadimastem receives US patent for amyotrophic lateral sclerosis (ALS) treatment. News release. Kadimastem Ltd. August 9, 2022. https://www.kadimastem.com/post/kadimastem-receives-us-patent-for-a-treatment-of-amyotrophic-lateral-sclerosis-als
2. Encouraging results of Cohort B of its phase 1/2a clinical trial of AstroRx for ALS. News release. Kadimastem Ltd. December 15, 2020. https://www.kadimastem.com/post/encouraging-results-of-cohort-b-of-its-phase-1-2a-clinical-trial-of-astrorx-for-als