AstroRx for ALS
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What is AstroRx for ALS?
AstroRx is an investigational cell-based therapy that is being tested in early clinical trials for amyotrophic lateral sclerosis (ALS). It aims to slow ALS progression by preventing further damage to nerve cells.
Developed by Kadimastem, the therapy received orphan drug designation from the U.S. Food and Drug Administration in 2018, which provides a range of incentives to accelerate its development for ALS.
Therapy snapshot
| Treatment name: | AstroRx |
| Administration: | An intrathecal (into-the-spinal-canal) injection |
| Clinical testing: | Completed a Phase 1/2a trial in Israel; a Phase 2a study in the U.S. is being planned |
How does AstroRx work in ALS?
ALS is a neurodegenerative condition in which motor neurons — the nerve cells that control muscle movement — become progressively damaged and die, leading to worsening muscle weakness and other symptoms.
The exact causes of ALS are not fully understood, but malfunctioning astrocytes are believed to contribute to disease processes.
Astrocytes are star-shaped cells found in the brain and spinal cord that are needed to maintain a healthy brain environment. In healthy people, these cells promote motor neuron health and survival through multiple mechanisms — including secretion of neuroprotective molecules, boosting nerve cell repair, modulating the immune system, and clearing up toxic molecules in the brain.
In ALS, however, astrocytes go haywire and acquire characteristics that contribute to nerve cell damage and disease progression.
AstroRx is a cell-based therapy designed to compensate for the malfunctioning astrocytes in ALS and to help prevent further damage to motor neurons.
The cells in AstroRx are derived from human embryonic stem cells, which are cells found in embryos during prenatal development that are able to grow into every single type of cell found within the human body. These stem cells are given molecular cues in the lab to turn into astrocyte progenitor cells, which then mature into fully functional astrocytes.
After being expanded to several millions, AstroRx cells are stored in vials for administration into the patient’s spinal canal. This creates an off-the-shelf product that can be immediately used in patients, in contrast to the lengthy process of creating astrocytes from a patient’s own cells.
How will AstroRx be administered in ALS?
AstroRx is an off-the-shelf product that is administered via an intrathecal (into-the-spinal-canal) injection, which delivers the cells to the cerebrospinal fluid, the liquid surrounding the brain and spinal cord.
In ALS clinical trials, the medication has been tested as a single injection containing 100 million or 250 million cells. To prevent an immune reaction against AstroRx cells, patients also receive the immunosuppressive drug mycophenolate mofetil starting two days before the injection and continuing for one month thereafter.
A planned clinical trial now will investigate AstroRx injections given every three months, but the optimal dose and treatment schedule have not yet been announced.
AstroRx in ALS clinical trials
The effectiveness of AstroRx was first tested in animal models of ALS, where the therapy significantly delayed disease onset and improved motor function compared with a sham treatment. This led Kadimastem to begin testing it in clinical trials for ALS patients.
Phase 1/2 trial
A Phase 1/2a clinical trial (NCT03482050), conducted at a single site in Israel, tested escalating doses of AstroRx in people with early ALS — those diagnosed with the disease less than two years before trial enrollment.
A total of 10 patients were included. After an initial run-in period of three months to determine their rate of disease progression, five patients received a single dose of 100 million AstroRx cells (low dose) and five were given an injection containing 250 million cells (high dose).
During the trial, all participants continued to receive stable treatment with Rilutek (riluzole). After the injection, they were monitored for up to one year.
Results showed both doses significantly reduced the rate of disease progression, as measured with the ALS Functional Rating Scale Revised (ALSFRS-R), three months after the injection.
In the low-dose group, AstroRx slowed the decline from a mean of 0.88 points per month in the run-in period to 0.30 points per month over the first three months, representing a 66% reduction in the rate of disease progression. The high-dose treatment slowed that decline by 45%, from a mean of 1.43 points per month before treatment to 0.78 points per month in the first three months. Combined, the two doses led to a 53% reduction in the rate of ALS progression.
The slowing in disease progression was particularly pronounced in people 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%.
While AstroRx’s impact was significant in the first three months, effects wore off thereafter. Assessments at five and six months and at one year showed that rates of progression had returned to pretreatment levels in all groups — indicating a need for repeat dosing.
The Phase 1/2a trial was originally 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 two months apart. However, these additional groups were not treated due to restrictions related to the COVID-19 pandemic.
Future trials
Kadimastem is now planning to conduct a Phase 2a clinical trial at multiple sites in the U.S. that will test repeat dosing of AstroRx in ALS patients. The trial, which has been cleared by the U.S. Food and Drug Administration, will investigate dosing in three-month intervals.
Common side effects of AstroRx
A single administration of AstroRx was found to be safe and well tolerated in a Phase 1/2a clinical trial. All patients experienced a treatment-emergent adverse event, but none of these side effects were deemed associated with the cell-based therapy.
The most common side effects reported, all of which were mild to moderate in severity, included:
- headache associated with the intrathecal injection
- pain in the injection site
- joint and back pain
- muscle contraction
- leg pain.
ALS News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about AstroRx
AstroRx is an investigational therapy that is still in clinical testing and not yet approved for amyotrophic lateral sclerosis (ALS). The cell-based therapy is made of functional astrocytes, cells that provide support to nerve cells in the brain and spinal cord but are malfunctioning in ALS patients. By compensating for the abnormal astrocytes, AstroRx cells are expected to prevent further nerve damage, which may potentially help slow disease progression.
It is still too early to know if or when AstroRx might be approved by the U.S. Food and Drug Administration. The cell-based therapy significantly slowed disease progression over three months in an early Phase 1/2a clinical trial, but repeat dosing might be needed to sustain those therapeutic effects. Additional studies will be needed before any application for approval can be submitted.
In amyotrophic lateral sclerosis (ALS) clinical trials, emergent side effects after treatment with AstroRx were not deemed related to the cells themselves but rather with the injection into the spinal canal. The most common side effects included headache associated with the injection, pain at the injection site, muscle contraction, and joint, back, and leg pain. It is recommended that patients consult with their healthcare team to know which side effects could be expected after treatment with AstroRx and how to manage them.
No studies have properly addressed the interaction between alcohol and AstroRx, so it is not known if patients receiving the cell-based therapy can safely drink alcohol. Patients should speak with their doctor if they are planning to drink while on this therapy.
In an early Phase 1/2a clinical trial, treatment with AstroRx resulted in significant reductions in the rate of disease progression in the first three months after treatment. However, it’s not yet clear how soon a significant effect in disease progression was observed in these patients. Additional analyses will be needed to better understand when an effect may become evident.
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