Neuronata-R improved function, survival in slow-progressing ALS
ALSummit trial did fail to meet its primary goal in the overall study population
Neuronata-R (lenzumestrocel), an investigational stem cell therapy from Corestemchemon significantly improved function and reduced markers of nerve cell damage in a subgroup of people with slow-progressing amyotrophic lateral sclerosis (ALS), the final results of a Phase 3 clinical trial show.
The ALSummit trial (NCT04745299) failed to meet its primary goal — a combined assessment of function and survival known as CAFS — in the overall study population. However, significant improvements were seen in this and other clinical measures in a subgroup with slowly progressing disease. The recent data comes from a post hoc analysis, or one conducted after the trial has ended and all the data have been gathered. The company plans to meet with the U.S. Food and Drug Administration (FDA) this year to discuss these findings, with the goal being to submit a biologics license application by year’s end and possibly gaining accelerated approval by mid-2026.
Neuronata-R was approved in South Korea for ALS in 2014 and has since been used by more than 400 patients in the clinic with no reports of serious side effects related to treatment. Corestemchemon now seeks to bring the therapy to ALS patients in the U.S. using a regulatory strategy similar to that employed for Qalsody (tofersen), which received accelerated approval based on reductions in the neurofilament light chain (NfL), a marker of nerve damage, rather than traditional clinical endpoints.
“This subgroup analysis lends strong support to a biomarker-driven approval strategy,” a company official said in a press release sent to ALS News Today.
ALS is caused by the progressive loss of nerve cells involved in movement, leading to muscle weakness and wasting, and gradually worsening problems with moving, swallowing, breathing, and speaking.
Effects on ALS patients with slower disease progression
Neuronata-R is a cell-based therapy that uses mesenchymal stem cells (MSCs) to reduce inflammation and improve nerve cell function and survival. MSCs are adult stem cells that can mature into many cell types and are known to secrete factors that modulate inflammation and improve neuronal health. The cells are obtained from a patient’s bone marrow, the spongy tissue found inside bones, and are then expanded in the lab and returned to the patient via intrathecal injections, that is, into the spinal canal.
In a previous Phase 1/2 clinical trial (NCT01363401), two Neuronata-R injections significantly slowed disease progression over a placebo for at least six months, as measured by ALS Functional Rating Scale Revised (ALSFRS-R) declines. ALSummit was designed to confirm these findings in a larger patient population and over a longer follow-up. It enrolled about 115 adults who’d been diagnosed within two years and whose disease was progressing at a rate of about one ALSFRS-R point per month.
The participants were randomly assigned to one of three groups. One received two Neuronata-R injections followed by three placebo injections; one was given five Neuronata-R injections, while a control group received five placebo injections. In all three groups, the first two injections were given 26 days apart and the remaining ones every three months (at 4, 7, and 10 months).
Top-line results announced last year indicated the primary endpoint — CAFS, a functional assessment that combines ALSFRS-R scores and survival — wasn’t met in the overall population.
Data from additional analyses wherein the patients given Neuronata-R were divided based on the rate of disease progression showed that those who progressed more slowly had significant improvements in CAFS, along with slower declines in ALSFRS-R scores and lung function.
Significant improvements were observed in those who progressed slowly in both treatment groups, but those who received five injections of the stem cell therapy tended to see greater benefits. For example, the five-dose group began showing significant improvements in ALSFRS-R by the ninth month, while the two-dose group showed gains at the 10th month.
Lung function also improved in the five-dose group, with differences from the placebo emerging after about eight months. At six months, significant improvements in CAFS were observed in both groups.
NfL levels were significantly reduced in both treatment groups, especially in the five-dose group, at both four and 10 months. This dose-dependent reduction supports the therapy’s biological activity and mirrors the biomarker-based approval strategy used for Biogen’s tofersen.
Those who progressed slowly also had a significant reduction in NfL. Again, greater benefits were seen in the five-dose group, suggesting a dose-dependent effect. In this group, NfL levels were significantly lower than in the placebo group at both four and 10 months.
Corestemchemon is finalizing its FDA submission package in collaboration with a global contract research organization and plans to engage with other regulatory agencies to gain Neuronata-R’s approval worldwide.
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