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<a href="https://www.kadimastem.com/">Kadimastem</a> is planning a Phase 2a clinical trial to test if repeat dosing of AstroRx, its investigational therapy for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), can continuously delay the disease&#8217;s progression.
The study will investigate every three-month dosing after findings from an earlier <a href="https://clinicaltrials.gov/ct2/show/NCT03482050">Phase 1/2 trial (NCT03482050)</a> showed a single infusion led to a clinically meaningful <a href="https://alsnewstoday.com/news/astrorx-safe-slows-als-progression-phase-1-2-clinical-trial/">decline in disease progression</a> over the first three months, but lost effectiveness later on.
The company recently submitted an investigational new drug (IND) application asking the U.S. Food and Drug Administration (FDA) to clear the trial.
“The submission of an IND to the FDA is a major milestone. It is very exciting to have arrived at this juncture. We eagerly await the approval to start this trial and wanting to help ALS patients as soon as possible,” said Michel Revel, MD, PhD, founder and chief scientific officer at Kadimastem, in a <a href="https://www.kadimastem.com/post/kadimastem-submits-ind-application-to-the-fda-for-its-phase-iia-clinical-trial-with-astrorx-for-als">company press release</a>.
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AstroRx is an off-the-shelf, investigational cell therapy composed of healthy astrocytes derived from human embryonic stem cells. Astrocytes are star-shaped cells that support nerve cells in the brain and spinal cord, but are believed to go awry in ALS and contribute to disease progression.
Injected directly into the spinal canal (intrathecal administration), it&#8217;s expected to make up for the faulty astrocytes, preventing further damage to nerve cells and slowing disease progression.
AstroRx&#8217;s safety and preliminary signs of efficacy were investigated in the Phase 1/2 study in Israel, which enrolled 10 patients who&#8217;d been diagnosed with ALS in the past two years.
After an initial monitoring period of three months, patients were equally divided to receive a single dose of 100 million AstroRx cells (low dose) or 250 million AstroRx cells (high dose) and were monitored for up to a year.
Results from the open-label trial showed both doses induced a significant decrease in the rate of disease progression over the first three months — a 53% reduction. However, no benefits were observed in either group after six and 12 months&#8217; follow-up, suggesting repeat dosing is necessary to maintain its efficacy.
“For the last year, we’ve reported our plans to submit an IND to the FDA with AstroRx for the treatment of ALS. The submission of the IND marks a significant milestone for the company, and subject to the approval of the FDA we hope to commence this very important multi-site trial and to bring this potential life enhancing therapy to the market and to patients as soon as possible,” said Ronen Twito, Kadimastem’s board executive chairman.
The investigational cell therapy was granted a U.S. patent <a href="https://alsnewstoday.com/news/als-cell-therapy-maker-kadimastem-awarded-patent-astrorx/">in August 2022</a> for treating ALS and other neurodegenerative diseases. Patents are also in place in Japan and Israel. The company also continues to advance its diabetes program, according to Kadimastem CEO Asaf Shiloni.

Kadimastem asks for FDA to clear new AstroRx clinical trial

<a href="https://www.kadimastem.com">Kadimastem</a>’s experimental cell-based therapy <a href="https://alsnewstoday.com/stem-cell-gene-therapy-for-als/astrorx/">AstroRx</a> was safe and significantly slowed disease progression in the first three months among people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), a Phase 1/2 clinical study shows.
The findings are in line with <a href="https://alsnewstoday.com/news/astrorx-slows-als-progression-at-all-doses-tested-trial-shows/">initial data</a> released by the company in 2020, with AstroRx more than halving the rate of disease progression when given at either a low or high dose. However, the therapy&#8217;s  benefits began to wane after the first three months, with the rate of disease progression at six months being similar to that observed before treatment.
Results indicate that repeat injections of AstroRx “may prolong its beneficial effect in ALS,” researchers wrote. The company now plans to launch <a href="https://alsnewstoday.com/news/als-cell-therapy-maker-kadimastem-awarded-patent-astrorx/">Phase 2a clinical study</a> in the U.S. to examine the effects of AstroRx injections given every three months.
The study’s full data, “<a href="https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03903-3">Safety and efficacy of first-in-man intrathecal injection of human astrocytes (AstroRx) in ALS patients: phase I/IIa clinical trial results</a>,” were now published in the <a href="https://translational-medicine.biomedcentral.com">Journal of Translational Medicine</a>.
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Astrocytes are star-shaped cells that support the survival and normal function of nerve cells in the brain and spinal cord. In ALS, however, astrocytes are thought to go awry and contribute to disease progression.
AstroRx contains healthy astrocytes derived from human embryonic stem cells, which can mature into multiple cell types. Given directly into the spinal canal via an intrathecal injection, AstroRx is expected to make up for the lack of functional astrocytes in ALS patients and prevent further damage to nerve cells.
“A cell therapy approach that includes intrathecal injection of healthy and functional astrocytes may compensate for the diseased endogenous astrocytes and attenuate the disease progression,” the researchers wrote.
The safety and preliminary signs of efficacy of AstroRx were investigated in a <a href="https://clinicaltrials.gov/ct2/show/NCT03482050">Phase 1/2 trial (NCT03482050)</a> in Israel. The open-label study included 10 patients, whose mean age was in the early 60s, and who had been diagnosed with ALS within the past two years.
<h3>Different doses of AstroRx</h3>
Participants were monitored monthly over a run-in period of three months to determine their rate of disease progression. Then, five patients received a single dose of 100 million AstroRx cells (low dose), and five patients received the high dose of 250 million AstroRx cells. After the injection, they were monitored for up to one year.
Results showed that both low- and high-dose AstroRx induced a significant decrease in the rate of disease progression.
Over the run-in period, patients in the low-dose group lost a mean of 0.88 points per month on the ALS Functional Rating Scale Revised (ALSFRS-R), a validated measure of disease progression. That decline fell to a mean of 0.30 points per month over the first three months after the injection — a significant, 66% reduction in the rate of disease progression.
Similar observations were made in the high-dose group, where the rate of ALSFRS-R declines dropped from a mean of 1.43 points per month in the run-in period to a mean of 0.78 points per month in the first three months after treatment — a 45% reduction.
Combined data from the two groups showed that AstroRx more than halved the rate of disease progression — a 53% reduction — over the three months after the injection. The effect was even more pronounced in a group of patients with rapidly progressing disease — defined as a decline of 1.1 ALSFRS-R points or more per month in the run-in period — in whom the rate of progression was lowered by 58%.
However, the effect was not maintained at the six- and 12-month follow-up visits, with rates of progression going back to those observed in the run-in period in all groups.
Similar improvements after three months and wearing off at six and 12 months were observed in muscle strength tests, although the differences at three months failed to reach statistical significance.
<h3>Study&#8217;s scope amended</h3>
The study initially planned to included two more groups of patients to investigate the impact of two injections of low- or high-dose AstroRx given two months apart. However, this part of the study was not conducted due to COVID-19 restrictions in place at the time.
All patients reported at least one side effect, but none was deemed related to AstroRx. Half of the patients reported a headache after the injection. Other side effects related to the injection included pain at the injection site, joint pain, back pain, and muscle contraction. All “were mild to moderate, and all resolved either spontaneously or with treatment,” the researchers wrote.
Three patients — one in the low-dose group and two in the high-dose group — died during the course of the study due to <a href="https://alsnewstoday.com/symptoms-of-als/#Breathing_difficulties">breathing difficulties</a> resulting from disease progression.
&#8220;To further determine the clinical effect of AstroRx in ALS, additional powered, controlled clinical studies to evaluate repeated administration of AstroRx, e.g. every 3 months, are required,&#8221; the team concluded.

Tag: Kadimastem

Kadimastem asks for FDA to clear new AstroRx clinical trial

AstroRx slows ALS progression in Phase 1/2 study