AstroRx Increases Ability to Perform Daily Functions in ALS Patients, Trial Results Show

Amyotrophic lateral sclerosis (ALS) patients receiving the lowest dose of Kadimastem’s cell therapy candidate, AstroRx, experienced a significant reduction in disease progression in the three or four months after treatment, updated findings from the company’s Phase 1/2 clinical trial show.

In subsequent months, however, the disease deteriorated at similar rates as before treatment, suggesting that repeat dosing or higher doses — both being tested in the ongoing trial — may increase AstroRx’s effectiveness.

No serious treatment-related adverse events or dose-limiting toxicities were reported in the first group of patients at least six months after treatment, suggesting that the lowest dose (100 million cells) is safe and well-tolerated.

“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,” Marc Gotkine, MD, department of neurology at Hadassah Medical Center, Jerusalem, said in a press release.

“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,” said Gotkine, who also is the principal investigator of the trial. “The trial is now continuing with higher doses and repeated injections.”

AstroRx is a cell therapy made of healthy, mature astrocytes, which are star-shaped cells of the central nervous system that normally maintain a healthy brain environment but are abnormal in ALS patients, contributing to disease progression.

The off-the-shelf therapy is derived from human embryonic stem cells and is expected to compensate for diseased astrocytes, preventing the loss of motor nerve cells when injected into a patient’s spinal fluid.

Studies in animals showed that AstroRx is safe and can delay ALS onset, maintain muscle function and increase survival. This led the biotech company in Israel to open a single-site Phase 1/2a clinical trial (NCT03482050) evaluating escalating doses of AstroRx in ALS patients.

The open-label study is being conducted at the Hadassah Ein-Kerem Medical Center and is expected to enroll 21 people with early stage disease. Recruitment is ongoing.

The main goal is to determine safety and tolerability of the therapy. Secondary measures include changes in patients’ ALS Functional Rating Scale revised (ALSFRS-R) scores, respiratory muscle strength, hand grip strength, limb muscle strength, and quality of life.

The company shared data from the first five patients included in the trial, all of whom received a single infusion of 100 million cells – the lowest dose of AstroRx tested – and were followed for at least six months after treatment.

After confirming the treatment’s safety, researchers assessed its efficacy and the duration of therapeutic effects – measured through changes in ALSFRS-R scores, which cover speech, swallowing, dressing and hygiene, among other daily functions.

In the three months preceding AstroRx’s treatment, patients’ ALSFRS-R score dropped by 0.87 points per month, on average, a similar decline in functional status as described in prior ALS studies.

In the three months after treatment, however, ALSFRS-R raised by an average of 0.26 points per month, suggesting that patients’ ability to perform daily activities increased in this period.

Researchers also examined the average ALSFRS-R change at four, five, and six months after treatment. While the rate of disease progression was still significantly lower in the first four months than before treatment (with an average decline of 0.32 points per month), at five and six months it was similar to the pre-treatment period.

That indicates this dose of AstroRx is effective only for a period of three or four months, after which patients see their disease deteriorate at a similar rate as before treatment.

“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,” said Rami Epstein, CEO of Kadimastem. “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.”

The trial is now assessing a higher dose of the therapy (250 million cells) in another group of five patients, all of whom have been enrolled. Kadimastem has recruited the first patient into a third group that will receive two AstroRx injections of 100 million cells, separated by two to three months months.

Results from the second and third groups are expected by August and the first half of 2021, respectively. Pending positive safety and effectiveness results, a fourth group will receive two injections of 250 million cells.

“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,” said Michel Revel, MD, PhD, founder and chief scientific officer of Kadimastem. “Both cohort[s] 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,” he said.