Pluri enters deal to manufacture Kadimastem’s AstroRx for ALS
Kadimastem to expand clinical testing of AstroRx to US sites
Kadimastem has partnered with Pluri to produce its investigational cell-based therapy AstroRx for an upcoming Phase 2a clinical trial in amyotrophic lateral sclerosis (ALS).
Under the agreement, Pluri will manufacture AstroRx at its 47,000-square-foot cell-therapy production facility under current good manufacturing practices (GMP), a set of standards that help ensure consistent high quality and consistency in the production of pharmaceuticals.
The collaboration will leverage PluriCDMO, Pluri’s recently launched contract development and manufacturing organization platform to help companies manufacture their cell and gene therapies for preclinical and clinical studies as well as commercial purposes. It will help Kadimastem expand the clinical testing of AstroRx into U.S. sites, following clearance of its ALS Phase 2a trial by the U.S. Food and Drug Administration.
“Working with Pluri marks a pivotal milestone, enhancing Kadimastem’s capacity to manufacture our products under GMP conditions,” Ronen Twito, executive chairman and president of Kadimastem, said in a press release. “This collaboration is integral to our strategy as we prepare for clinical trials and expand into the U.S. market with our AstroRx product candidate.”
Astrocytes are star-shaped cells that support nerve cells in the brain and spinal cord in healthy people. However, in ALS, these cells malfunction, increasing nerve cell death and contributing to disease progression.
AstroRx is off-the-shelf cell-based therapy of healthy astrocytes
AstroRx is an off-the-shelf cell-based therapy containing healthy astrocytes that were derived from human embryonic stem cells.
The therapy is administered intrathecally, meaning it is injected into the spinal canal to deliver cells to the cerebrospinal fluid (i.e. the liquid surrounding the brain and spinal cord). Once in the body, AstroRx aims to compensate for the faulty astrocytes and limit further nerve damage to slow disease progression.
An earlier Phase 1/2a clinical trial (NCT03482050), conducted at a single site in Israel, tested AstroRx in 10 patients who had been diagnosed with ALS within the last two years.
Following an initial three-month run-in period to establish each person’s disease progression rate, five patients received a low dose (100 million cells) of AstroRx and the remaining five received a high dose (250 million cells) of the therapy.
After the intrathecal injection, patients were monitored for up to one year. During that period, those on stable doses of standard ALS medications — riluzole (sold as Rilutek and others) and/or Radicava (edaravone) — before entering the trial could continue to receive them.
AstroRx reduced rate of disease progression 3 months after injection
Three months after the injection, results showed AstroRx reduced the rate of disease progression by an average of 53%, as measured with the ALS Functional Rating Scale Revised (ALSFRS-R). Specifically, the low-dose group showed a 66% reduction in the rate of disease progression, while in the high-dose group, AstroRx slowed the decline by 45%.
Participants with rapidly progressing disease — defined as a decline of 1.1 ALSFRS-R points per month in the run-in period — had a particularly pronounced reduction in disease progression, by 58%, after three months.
However, treatment with a single dose of AstroRx at either dose did not result in significant long-lasting therapeutic benefits. When patients were assessed at five and six months, and at one year after the injection, rates of progression had returned to pretreatment levels in all groups.
To address these waning effects, efforts are underway to examine the effects of repeated AstroRx dosing in patients with ALS.
Kadimastem is planning to conduct a multi-site Phase 2a clinical trial in the U.S. to determine if AstroRx injections every three months would continue to delay the disease’s progression. Pluri’s facilities, which allow for production of the cell-based therapy at mass scale, will produce the cells required for this trial.
“We are excited to work with Kadimastem and support their development of cell therapies, potentially improving the lives of patients with ALS,” said Yaky Yanay, CEO and president of Pluri. “This collaboration underscores the versatility of our PluriCDMO platform and our commitment to aiding innovative companies in advancing their life-saving therapies.”
In addition to AstroRx, Pluri will also manufacture another cell therapy developed by Kadimastem, IsletRx, for diabetes.
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