No treatment-related serious adverse events nor dose-limiting toxicities were reported
A statistically significant decline in disease progression was observed during the first 3- 4 months post-treatment period, indicating a clinical benefit of the AstroRx® cell product, suggesting a higher dose and/or repeated treatments may achieve prolonged efficacy
First patient has been enrolled to cohort C which is designed to further assess safety and prolonged efficacy of repeated administrations
NESS ZIONA, ISRAEL – January 02, 2020 – Kadimastem Ltd. (TASE: KDST), a clinical stage cell therapy company, today announced promising results of cohort A of its Phase 1/2a clinical trial for the treatment of patients with Amyotrophic Lateral Sclerosis (ALS). The primary objective of the trial is to evaluate the safety of AstroRx®, an "off-the-shelf" clinical-grade astrocyte cell product, developed and manufactured by the Company. A secondary objective of the trial includes preliminary efficacy assessments. All 5 patients included in cohort A were treated with a dose of 100x106 AstroRx® cells and completed the 6 months post-treatment follow up period.
No treatment related serious adverse events (SAEs) nor dose-limiting toxicities were reported during the 6 months post-treatment follow up period of cohort A, suggesting a positive safety profile of the AstroRx® dose provided.
Efficacy analysis of the 6 months follow up period was performed to assess the time frame during which the treatment maintains its therapeutic effect. The efficacy assessment was based on ALS Functional Rating Scale-Revised (ALSFRS-R), the gold standard criteria to assess ALS progression by monitoring patient muscle functions over time. During the 3 months pre-treatment period, the ALSFRS-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 analysis examined the average rate of disease progression at 3, 4, 5 and 6-months post-treatment periods compared to the average rate during the 3-months pre-treatment period.
The average ALSFRS-R change in the 3 months post-treatment 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 3 months post-treatment period (p=0.0023).
The average ALSFRS-R change in the 4 months post-treatment period was (-0.32) per month. These results also indicate a statistically significant difference between the slope in the pre-treatment period and the slope in the 4 months post-treatment period (p=0.0447).
These findings indicate that for a period of 3-4 months following treatment the progression of the disease was reduced, providing a potentially meaningful clinical benefit to the patients.
In the 5- and 6-months post-treatment periods, a statistically significant difference was not observed between the rate of disease deterioration during these periods and the rate during the pre-treatment period.
These findings indicate a clinical benefit is achieved and sustained for a period of 3-4 months following treatment and further suggest a higher dose and/or repeated administrations may achieve prolonged efficacy. Furthermore, these findings align with the design of the clinical trial as planned for cohort B and C, respectively, as in cohort B the effect of a higher dose is assessed, and cohort C will examine the therapeutic effect of repeated treatments. In cohort B, treatment has been completed with a higher dose of 250x106 AstroRx® cells. First patient has already been enrolled to cohort C, which is intended to further assess safety and prolonged efficacy, with 2 consecutive injections of AstroRx® cells separated by an interval of 2-3 months.
"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, Department of Neurology at Hadassah Medical Center, Jerusalem, and the Principal Investigator of the trial. "These results on a small subset of patients of the first experimental group treated with 100 million AstroRx® cells are encouraging, as the treatment seems to be safe. After completion of 6 months follow up period, initial data analysis presented to us appears to demonstrate a transient efficacy benefit that lasted for 3-4 months post treatment as measured by ALSFRS-R deterioration rate. The trial is now continuing with higher doses and repeated injections".
Rami Epstein, CEO of Kadimastem, stated: "We are very encouraged by the final cohort A results, demonstrating AstroRx® provides a meaningful clinical benefit in terms of the ALSFRS-R rating scale. We look forward to continue our study, assessing the potential long-term benefits of a higher dose regimen as well as repeated administrations of our breakthrough Cell Therapy.”
Prof. Michel Revel, Founder and CSO of the Company, added, "These results clearly support a desirable safety profile of our AstroRx® astrocyte cell-based product. This provides the confidence needed to move forward to the repeated injections in the forthcoming cohort C. Since in cohort A the clinical response was clearly demonstrated to last for at least 3-4 months following cell injection, cohort B will include a higher dose of cells, and cohort C will include repeated injections with approximately 3-month intervals. Both cohort B and C hold a potential promise for a prolonged response. The positive safety profile also allows us to test AstroRx® in other neurodegenerative diseases.”
About the Phase 1/2a ALS Clinical Trial
The Phase 1/2a trial is an open label, dose escalating clinical trial intended to evaluate the safety and tolerability of AstroRx® cells in patients with ALS. The trial is expected to include 21 patients and is being conducted at the Hadassah Medical Center, Jerusalem, Israel. The primary endpoints of the trial are safety evaluation and tolerability of a single and repeated administrations of allogeneic astrocytes derived from human Embryonic Stem Cells (hESC), produced in accordance with a process developed by the Company and administered in escalating doses. Secondary endpoints include efficacy evaluation and measurements.
Treatment is administered in addition to the appropriate standard-of-care. An amendment to the protocol is in process. The purpose of the amendment is to assess the safety and efficacy of a repeated dose administration of 100x106 of AstroRx® in cohort C, in 2 consecutive injections, separated by an interval of 2-3 months, rather than the repeated administrations of the 250x106 dose, as originally planned. As part of the proposed protocol amendment, cohort D will include a repeated dose of (250x106) AstroRx® cells (as originally planned in cohort C). Performance of cohort D will be discretionary, based on the results of previous cohorts. Results of cohort B are expected to be reported during August 2020. Results of cohort C are expected in the first half of 2021.
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 cerebrospinal cord fluid (CSF) using standard lumbar puncture procedure, 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 trials and is currently undergoing a Phase 1/2a clinical trial. AstroRx® has been granted orphan drug designation by the FDA. Scientific literature indicates that astrocyte cells play a substantial role in supporting malfunctioning cells also in other neurodegenerative diseases, in addition to ALS. The Company is evaluating other potential applications of the AstroRx® cell product accordingly.
Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive fatal neurodegenerative disease causing dysfunction in the upper and lower motor nerves that control muscle function. ALS leads to muscle weakness, loss of motor function, paralysis, breathing problems, and eventually death. The average life expectancy of ALS patients is 2-5 years. According to the ALS Therapy Development Institute, it is estimated that there are approximately 450,000 ALS patients worldwide of which 30,000 reside in the US. According to the ALS Foundation for Life, the annual average healthcare costs of an ALS patient in the US are estimated at US$ 200,000. Thus, the annual healthcare costs of ALS patients in the US alone amount to US$ 6 Billion.
Kadimastem is a clinical stage cell therapy company, developing and manufacturing "off-the-shelf" allogeneic proprietary cell products based on its platform technology for the expansion and differentiation of Human Embryonic Stem Cells (hESCs) into clinical grade functional cells. AstroRx®, the Company's lead program, is a clinical-grade astrocyte cell therapy for the treatment of ALS, currently undergoing a Phase 1/2a clinical trial. Another program is the Company’s IsletRx pancreatic functional islet cells for the treatment of insulin dependent diabetes, which demonstrated safety and efficacy in a proof of concept preclinical trial. Kadimastem was founded by Prof. Michel Revel, CSO of the Company and Professor Emeritus of Molecular Genetics at the Weizmann Institute of Science. Prof. Revel received the Israel Prize for the invention and development of Rebif®, a multiple sclerosis blockbuster drug sold worldwide. Kadimastem is traded on the Tel Aviv Stock Exchange (TASE: KDST).
Forward Looking Statement
This document may include forward-looking information as defined in the Securities Law, 5728 – 1968. Forward-looking information is uncertain and mostly is not under the Company’s control and the realization or non-realization of forward-looking information will be affected, among other things, by the risk factors characterizing the Company’s activity, as well as developments in the general environment and external factors affecting the Company’s activity. The Company’s results and achievements in the future may differ materially from any presented herein and the Company makes no undertaking to update or revise such projection or estimate and does not undertake to update this document. This document does not constitute a proposal to purchase the Company’s securities or an invitation to receive such offers. Investment in securities in general and in the Company in particular bears risks. One should take into account that past performance does not necessarily indicate performance in the future.
Yossi Nizhar, CFO
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