Kadimastem Ltd, a clinical stage cell therapy company, has announced promising interim results with cohort A of its Phase 1/2a clinical trial for the treatment of patients with Amyotrophic Lateral Sclerosis (ALS).
Disease progression was reduced in the first three-month post-treatment period, compared to the three-month pre-treatment period. This preliminary result demonstrates a statistically significant decline in disease progression.
No treatment-related serious adverse events nor dose-limiting toxicities were reported.
Final results for cohort A are expected by year-end 2019; results for cohort B are expected in Q3 2020.
The primary objective of the trial is to evaluate the safety of injecting AstroRx®, an “off-the-shelf” clinical-grade astrocyte cell product, developed and manufactured by the Company, into the spinal cord fluid of ALS patients. A secondary objective of the trial includes preliminary efficacy.
An interim analysis to explore possible efficacy was initiated and conducted after all five patients in cohort A completed three months of post-treatment visits.
The five patients included in cohort A received the lowest dose of AstroRx® (100×106 cells). Preliminary efficacy assessment was based on ALS Functional Rating Scale-Revised (ALS-FRS-R), the gold standard criteria to assess ALS progression by monitoring patient muscle functions over time. During the three-month pre-treatment period, the ALS-FRS-R decreased at an average rate of -0.87 per month. This rate of decrease is similar to that reported in the scientific literature. The average ALS-FRS-R change in the three-month post-treatment period was +0.26 per month.
These results demonstrate a statistically significant difference between the slope in the pre-treatment period and the slope in the first three-month post-treatment period (p=0.0023). This indicates that the progression of the disease was reduced in the first post-treatment period compared to the pre-treatment period. Preliminary and interim results of Cohort A will be presented at the prestigious annual NEALS meeting to be held in Florida, at the beginning of October 2019. Final results for cohort A (total six months post-treatment period) are expected by year-end 2019.
Following the recommendation of the trial’s independent Data & Safety Monitoring Board (DSMB) and the approval of the Israeli Ministry of Health, all five patients for cohort B who will receive a higher dose of AstroRx® cells (250×106) were recruited.
“ALS is a devastating disease and there is a critical need for new treatments to more effectively slow down or halt its rapid progression,” stated Dr. Marc Gotkine, Hadassah Medical Center neurologist, head of its ALS Clinic, and the principal investigator of the trial. “These preliminary results on a small subset of patients are encouraging, as the treatment seems to be safe, at this lower dose. The initial data analysis presented to us appears to demonstrate a slowing down of the reported ALSFRS-r deterioration rate over the three months following treatment. The trial is now continuing with higher doses and repeated injections.”
Rami Epstein, Chief Executive Officer of Kadimastem, commented, “To the best of our knowledge, Kadimastem is the only company developing astrocyte-based cell therapy for the treatment of ALS, which may become a breakthrough in ALS treatment. “These results are not only an important milestone in our quest to bring treatment to ALS patients, but also serve as a validation of our unique technology platform and ability to develop and manufacture clinical grade cells in our GMP compliant facilities.”
Prof. Michel Revel, founder, and chief executive officer of the Company, stated, “These interim results show that our AstroRx® cell product, even at the lowest dose, has therapeutic effects. The scientific literature indicates that astrocyte cells play a substantial role in supporting malfunctioning cells also in other neurodegenerative diseases in addition to ALS. Therefore, we intend to study the potential therapeutic effect of our AstroRx® cells in additional neurodegenerative diseases.”
About the Phase 1/2a ALS Clinical Trial
The Phase 1/2a trial is an open label, dose escalating clinical study to evaluate the safety, tolerability, and preliminary efficacy of AstroRx® cells in patients with ALS. The trial is expected to include 21 patients and is being conducted at the Hadassah Medical Center. The primary endpoints of the trial are safety evaluation and tolerability of a single administration of allogeneic astrocytes derived from human Embryonic Stem Cells (hESC), administered in escalating low, medium, and high doses (100×106, 250×106, and 500×106 cells, respectively). The medium dose will also be administered in two consecutive injections, separated by an interval of 60 days. Secondary endpoints include efficacy evaluation and measurements. Treatment is administered in addition to the appropriate standard-of-care.
AstroRx® is a clinical grade cell therapy product developed and manufactured by Kadimastem in its GMP-compliant facility, containing functional healthy astrocytes (nervous system support cells) derived from human Embryonic Stem Cells (hESC) that aim to protect diseased motor neurons through several mechanisms of action. The Company’s technology enables the injection of AstroRx® cells into the spinal cord fluid of patients suffering from Amyotrophic Lateral Sclerosis (ALS) with the goal of supporting the malfunctioning cells in the brain and spinal cord, in order to slow the progression of the disease and improve patients’ quality of life and life expectancy. AstroRx® has been shown to be safe and effective in preclinical studies. AstroRx® has been granted orphan drug designation by the United States Food and Drug Administration.