Phase 3 Trial of Stem Cell Therapy NeuroNata-R Enrolling in Korea

Note: This story was updated March 31, 2021, to note that the ALSummit trial has been approved by the U.S. Food and Drug Administration but will proceed only in Korea; there are no plans to open additional sites in the U.S. or elsewhere.

A Phase 3 clinical trial is recruiting adults with amyotrophic lateral sclerosis (ALS) to evaluate the safety and effectiveness of NeuroNata-R (lenzumestrocel), a stem cell therapy approved to treat ALS in South Korea.

Enrollment is currently ongoing in South Korea, and patients interested in participating must be able to stay in the country for at least 14 months, Corestem, the therapy’s developer, stated in an email to ALS News Today.

ALS is a progressive neurodegenerative disorder caused by the gradual loss of motor neurons — the specialized nerve cells responsible for controlling voluntary movements — in the spinal cord and brain, leading to muscle weakness and shrinkage.

Stem cell therapy is emerging as a potential way of treating ALS. Taking advantage of stem cells’ unique ability to give rise to many types of specialized cells, the approach is expected to help regenerate damaged or dying neurons and key cells that support them.

NeuroNata-R, Corestem’s lead product, makes use of a patient’s own mesenchymal stem cells (MSCs), which are capable of maturing into many other cell types that may help to promote nerve cell repair.

The treatment involves isolating MSCs from a person’s bone marrow, growing them in the lab, and returning them to the patient, mixed with their cerebrospinal fluid (CSF), via an injection directly into the spinal canal. CSF is the liquid that surrounds the brain and spinal cord.

The first NeuroNata-R injection typically takes place one month after bone marrow extraction, followed by a second injection about a month later.

Prior studies highlighted the immunosuppressive, anti-inflammatory, and neuroprotective properties of NeuroNata-R. As such, the therapy is expected to promote motor neuron growth and prevent the death of these cells, slowing ALS progression.

The therapy was previously tested as an add-on to riluzole (marketed as Rilutek, Tiglutik, and Exservan) in a Phase 1/2 clinical trial (NCT01363401) conducted in South Korea.

Results showed that NeuroNata-R, given as two intrathecal (into the spinal canal) injections, safely and effectively slowed disease progression — as assessed with the ALS Functional Rating Scale (ALSFRS-R) — in 32 ALS patients for at least six months.

These findings supported the conditional approval of NeuroNata-R in South Korea in 2014 as the first stem cell therapy for ALS. Its continued use, and full approval, requires further verification and description of clinical benefit in a larger, longer-term confirmatory study.

It was designated an orphan drug as a potential ALS treatment in the U.S. in 2018, followed by a similar designation in Europe about six months later. Both designations are meant to accelerate its development and review.

Corestem also reports that both U.S. and Korean regulatory authorities have approved its request to conduct a Phase 3 clinical trial of NeuroNata-R in Korea.

This study, called ALSummit (NCT04745299) is designed to evaluate the long-term safety and effectiveness of NeuroNata-R in up to 115 adults, ages 25–75, diagnosed with ALS within the previous two years.

Participants will be randomly assigned to either NeuroNata-R — followed or not by three injections, given three months apart — or to a placebo injection (CSF without stem cells). All enrolled will also receive riluzole.

The trial’s main goal is to assess changes in a combined measure of function, based on the ALSFRS-R score, and survival benefits. Secondary goals include other measures of function and quality of life.

These assessments will be conducted at six months for patients receiving one treatment cycle, and at one year for those given three additional injections.

Eligible patients may also be asked to enter a supplementary study that will continue to week 48 (nearly a year), and long-term efficacy and safety will be evaluated during an observation period of 36 months from first NeuroNata-R injection.

According to Corestem, more than 300 ALS patients have been treated with NeuroNata-R in South Korea as of December, including at least 49 people who traveled from their home countries for the treatment.

“Not many patients are aware of the existence of Neuronata-R, so we are eager to let the community know its existence,” Eunsan Cho, the assistant manager of Corestem’s marketing team, said in the email.