Astrocyte Cell Therapy Temporarily Slows ALS Decline
No treatment-emergent adverse events experienced were deemed related to AstroRx, although 9 serious TEAEs did occur.
The astrocyte cell therapy AstroRx (Kadimastem) was well-tolerated and slowed the rate of decline on Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) scores at 3 months post-treatment, according to results from a phase 1/2 clinical trial (NCT03482050) recently published in Journal of Translational Medicine.1
“These results support a further need for a randomized-controlled, clinical trial with repeated doses of AstroRx® in patients with ALS, in order to prolong the clinical effect observed by a single dose," principal investigator Marc Gotkine, MD, Head, ALS Clinic, Department of Neurology, Hadassah Medical Center, Jerusalem, said in a statement.2
Gotkine and colleagues initially screened 24 patients with ALS and enrolled 5 patients in group A, 8 in group B, and 3 in group C.1 All patients in group A received a single administration of low-dose AstroRX (100 × 106 cells) injected into the spinal cord fluid using a standard lumbar puncture procedure; 4 were followed up for 6 months, and 3 enrolled in the extension study and were followed up for 12 months. Five patients in group B received a single administration of high-dose AstroRx (250 × 106 cells), completed 6 months of follow-up and continued to the extension study, and 3 completed 12 months of follow-up. Group C was set to receive 2 administrations of high-dose AstroRx but this cohort was discontinued due to the COVID-19 pandemic and no patients in this group were treated.
Altogether, treated patients experienced a total of 86 treatment-emergent adverse events (TEAEs) during the study -63 mild, 19 moderate, and 4 severe, none of which were deemed related to the AstroRX cell therapy. Nine serious TEAEs that were reported. The most common TEAE was post lumbar puncture headache, which was reported by half of the patients. Other common procedure-related REAEs included injection site pain (30%), arthralgia, back pain, pain in the leg and muscle contraction, each reported by 10% of patients. Four AEs were related to mycophenolate mofetil; these included headache, nausea, anemia, and hyperhidrosis. AEs related to immunosuppression were all mild to moderate and resolved. No clinically significant changes in lab assessments, vital signs, physical examinations, or ECG results were observed throughout the study and no tumor formations in the central nervous system were observed. There were 3 deaths during the study that took place 9 to 10 months after treatment due to respiratory failure associated with disease progression.
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In terms of efficacy, investigators observed an attenuation in rate of decline in ALSFRS-R scores in the first 3 months after treatment which was not maintained after this point. Mean decline attenuated from –0.88 per month in group A to –0.3 per month after 3 months (P = .039) for a 66% attenuation rate. This rate became -0.76 per month and -0.82 per month at months 6 and 12, respectively. Mean decline attenuated from –1.43 per month in group B to –0.78 per month at 3 months (P = .002) for a 45% attenuation rate. These rates were –1.59 per month and –1.29 per month at months 6 and 12. Combined, groups A and B had an attenuation rate of 53% in the first 3 months after AstroRx treatment (P <.001). Change in decline was also analyzed superficially in a subpopulation of 5 rapid progressors from both groups, whose rate of attenuation was 58% from –1.58 per month to –0.65 per month (P <. 001).
“We would like to thank the Hadassah Hospital clinical team, patients, and their families for their contribution. These are the fruits of Kadimastem's dedicated team. We are very excited to move toward our next Phase IIa clinical study with new off-the-shelf (“thaw and inject”) AstroRx® cell product which will be tested using repeated intrathecal injections of AstroRx,” Michal Izrael, vice president, research and development, Kadimastem, added to the statement.2
AstroRx is set to be further evaluated in a phase 2a trial to be conducted in the US, unlike the initial trial, which was conducted in Israel.3 The FDA approved the investigational new drug application (IND) for the trial in March 2023 to evaluate repeated doses of AstroRx in patients with ALS in 3-month intervals.
“The approval of submission of the IND to the FDA is a major achievement and moment of pride for me in the company that I have founded [sic] years ago, with an amazing team. It is very exciting, and we eagerly await tostart this trial and wish to help ALS patients as soon as possible,” Professor Michel Revel, Founder and Chief Scientific Officer, Kadimastem, said in a statement about the IND approval.3
