AstroRx Slows ALS Progression at All Doses Tested, Trial Shows

AstroRx Slows ALS Progression at All Doses Tested, Trial Shows
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Kadimastem’s cell therapy candidate, AstroRx, significantly lowers the rate of disease progression in people with amyotrophic lateral sclerosis (ALS) for at least three months after treatment, updated findings from the company’s Phase 1/2 clinical trial show.

The company already had reported promising efficacy results in patients receiving the lowest dose of AstroRx, and recent findings from the highest dose group suggests it slows functional decline by more than 50% in both groups, with greater benefits in rapid progressors.

As in the first group of patients, no serious treatment-related adverse events (side effects) or dose-limiting toxicities were reported in the second group, suggesting that the treatment also is safe and well-tolerated at higher doses.

“We are excited by the positive and consistent clinical results, demonstrating both the good safety profile and therapeutic effect of AstroRx,” Rami Epstein, Kadimastem CEO, said in a press release.

“The comparison between the ALSFRS-R change before and after treatment convey a clinically meaningful decline of more than 50% in disease progression rate for a period of 3 months for both cohorts,” Epstein said. “The effect was even more profound in patients who deteriorate rapidly.”

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 so-called “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.

The ongoing Phase 1/2 trial (NCT03482050), conducted at the Hadassah Ein-Kerem Medical Center, Israel, was designed to investigate the safety and efficacy of escalating doses of AstroRx in ALS patients with early stage disease.

Its main goal is to determine the safety and tolerability of the therapy. Secondary measures include changes in patients’ ALS Functional Rating Scale revised (ALSFRS-R) scores — covering speech, swallowing, dressing and hygiene, among other daily functions — as well as measures of muscle strength and quality of life.

Results from the first five patients included in the trial, all of whom received a single infusion of 100 million cells, already had shown that AstroRx slows the rate of disease progression in three-four months after treatment, but that rates of disease progression return to baseline after that period.

In the three months preceding AstroRx’s treatment, these patients were experiencing an average reduction in their ALSFRS-R scores of 0.87 points per month, but their scores raised by an average of 0.26 points per month in the three months after treatment, suggesting that patients gained some ability to perform day-to-day activities in that period.

While benefits from AstroRx were still observed at month four, they wore off after that, suggesting that repeat dosing may increase the therapy’s effectiveness.

The latest data

The company now has shared data from the second group of five patients, who were progressing at a rate of 1.43 ALSFRS-R points per month in the three-four months before treatment, and received a single administration of 250 million cells.

However, in the three months that followed treatment, the average drop in ALSFRS-R was significantly lower: 0.78 points per month, representing a 45% reduction in disease progression rate.

Results were even better when researchers estimated the rate of disease progression onward from day 30 after treatment. In this analysis, ALSFRS-R scores dropped by 0.41 points per month after treatment, a 71% slower decline in functional ability compared with baseline progression.

Final results from this group are expected by year’s end.

A pooled analysis of all 10 patients included in the trial then showed that AstroRx reduced the disease progression rate by 53%, from a drop of 1.15 ALSFRS-R points per month pre-treatment to drops of 0.54 points per month post-treatment.

Also, 70% of patients experienced at least a 25% reduction in their progression rate after receiving AstroRx, and were identified as responders.

Of the 10 patients, five were considered fast progressors, meaning that their ALSFRS-R scores were deteriorating by at least 1.1 points per month before receiving treatment. In these patients, 80% were responders and their rate of disease progression declined by 59% after receiving AstroRx (from 1.58 points per month to 0.65 per month).

In total, these patients had experienced an average reduction of 4.74 points in the three months before treatment. In the three months after treatment, however, only 2.77 points were lost, on average — 1.97 less than in an identical period without AstroRx.

“The current study results are encouraging, as they suggest a clinically meaningful signal of effect. A further randomized, parallel-controlled, clinical trial is needed to confirm these positive effects of AstroRx in the treatment of ALS,” said Marc Gotkine, MD, the trial’s principal investigator.

The trial originally was designed to include two additional groups of patients, one receiving two infusions of 100 million cells, and another given two infusions of 250 million cells. However, the company decided not to enroll these additional patients in the Phase 1/2 trial due to the COVID-19 situation in Israel. Rather, repeated dosing will be assessed in upcoming trials.

“Repeated administrations of the treatment, planned to be assessed in future clinical trials, will hopefully extend the duration of the beneficial effect,” said Epstein. “These results strengthen our commitment to bringing an innovative therapeutic treatment to ALS, a devastating disease currently having no effective treatment.”

The company is working to increase the production of AstroRx and to produce a frozen formulation of this therapy, which will support its regulatory approval, Kadimastem said.

Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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Ana holds a PhD in Immunology from the University of Lisbon and worked as a postdoctoral researcher at Instituto de Medicina Molecular (iMM) in Lisbon, Portugal. She graduated with a BSc in Genetics from the University of Newcastle and received a Masters in Biomolecular Archaeology from the University of Manchester, England. After leaving the lab to pursue a career in Science Communication, she served as the Director of Science Communication at iMM.
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Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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