Kadimastem plans to submit an amendment to the protocol of its ongoing Phase 1/2a trial in Israel assessing the use of AstroRx, an “off-the-shelf” stem cell therapy, for the treatment of amyotrophic lateral sclerosis (ALS).
The company wants to change the planned dosage in one of the study’s cohorts and test repeated injections of a low dose of AstroRx, instead of the medium dose that was originally planned.
The request is based on positive interim data from the first set of five patients given a single intrathecal (into the spinal canal) injection of the lowest dose (100 x 106 cells) of AstroRx. At this dose, the therapy was found to be safe with no serious side effects or dose-limiting toxicities identified, according to the data, which was released in September.
Moreover, AstroRx significantly reduced disease progression after three months of treatment, compared to the start (baseline) of the trial. The ALS Functional Rating Scale revised (ALSFRS-R) score decreased on average by 0.87 per month during the three months before treatment; however, it started to increase again (on average by 0.26 per month) in the three months after treatment. The ALSFRS-R score is a validated assessment of disability progression, with lower scores indicating greater motor impairment.
Evidence suggests that poorly working astrocytes (cells which support and protect neurons) are involved in the progression of ALS. AstroRx is composed of healthy functional astrocytes, which have been derived from human embryonic stem cells. The treatment, injected into a patient’s spinal fluid, is thought to compensate for the diseased astrocytes and prevent the death of motor neurons, thereby slowing disease progression.
AstroRx was granted orphan drug status by the U.S. Food and Drug Administration in November 2018 for the treatment of ALS.
Preclinical (in the lab) studies have shown that AstroRx was safe, delayed disease onset, maintained muscle function, and increased survival in rodent models of ALS.
The ongoing open-label Phase 1/2a clinical trial (NCT03482050) is testing the safety and effectiveness of AstroRx in ALS patients. The trial is being conducted at Hadassah Ein-Kerem Medical Center in Israel where it recruited 21 patients with early stage disease.
The trial’s original protocol included four doses of AstroRx delivered into the spinal canal: a low (100 x 106 cells), medium (250 x 106 cells), or high (500 x 106 cells) dose.
The primary outcome of the trial is to assess the safety and tolerability of AstroRx. Secondary outcome measures include changes in patients’ ALSFRS-R scores, respiratory muscle strength, hand grip strength, limb muscle strength, and quality of life.
In cohort A, participants received a single low dose of the therapy. In cohort B, participants received a single medium dose of the therapy. Results from cohort A are expected to be reported by the end of 2019, and cohort B results are expected in 2020.
Based on the positive interim results from cohort A, Kadimastem is seeking to amend the therapy regime being assessed in cohort C and D, so that cohort C will receive two injections of the low dose (instead of the originally planned medium dose), with the injections being separated by two to three months. Results from this section of the trial are expected to be reported in the first half of 2021. Under the amendment, cohort D participants will receive the regimen originally planned for cohort C (repeated administration of the medium dose, 250 x 106). Cohort D dosing will be dependent on the results of the previous cohorts.
“We are the first to treat ALS patients with astrocyte cells. Following our positive interim results, we look forward to achieving a prolonged therapeutic effect in the repeated low dose administration, bringing new hope for patients with this incurable disease” Rami Epstein, CEO of Kadimastem, said in a press release.
Kadimastem expects to submit an investigational new drug application to the U.S. Food and Drug Administration by mid-2021 with the aim of testing AstroRx in a multi-center clinical trial, which will compare the current and frozen version of the therapy.