Background
Neuronata-R or Lenzumestrocel is an autologous bone marrow-derived mesenchymal stem cell product for treating Amyotrophic Lateral Sclerosis (ALS) developed by Corestem Chemon. Lenzumestrocel is administered via intrathecal injection and aims to slow ALS/MND progression by targeting neuroinflammation, promoting neuroprotection and preventing motor neuron death (Corestem Chemon website).
Lenzumestrocel was conditionally approved as on orphan drug for the treatment of ALS/MND by the South Korean Ministry of Food and Drug Safety (MFDS, Republic of Korea) in 2013, expecting the data to support a potential full approval in South Korea (Oh et al., 2015).
| Approved In: | Commercial Name: |
| South Korea | NeuroNata-R |
Proposed Mechanism of Action
Lenzumestrocel utilizes autologous bone marrow-derived mesenchymal stem cells (MSCs), which are adult stem cells capable of self-renewal and division. The treatment is prepared extracting bone marrow from the treated person, isolating and culturing the MSCs, and mixing them with cerebrospinal fluid (CSF – collected through spinal tap) from the same individual before administering the final product via intrathecal injection. The first injection of Lenzumestrocel typically occurs about four weeks after the initial bone marrow extraction, followed by a second injection four weeks later. The treatment is thought to target several biological pathways that may stimulate the growth of new nerve cells and regulate the immune response to damaged cells. Additionally, MSCs are thought to produce a range of molecules with modulatory effects, including the release of immune-modulating factors, putatively resulting in a protective effect on motor neurons through the expression of growth factors, and an anti-inflammatory effect (Corestem Chemon press release, Oh et al., 2018).
Clinical Trials
A phase 1 open-label trial assessed the safety and practicality of administering two intrathecal injections of autologous bone marrow-derived mesenchymal stem cells (MSCs) over 12 months in eight people living with ALS/MND. Of the eight people, seven received intrathecal injections and one passed before the first administration. No serious adverse events were observed in the 12 month follow-up period (Oh et al., 2015).
Building on these results, a phase 2 randomized controlled trial with parallel groups (Clinicaltrials.gov ID: NCT01363401) was conducted in 64 participants with a 1:1 treatment to control ratio. Lenzumestrocel was considered safe and well tolerated and, when compared to the control group (n=27), people in the Lenzumestrocel treated group (n=32) showed smaller decline in their ALSFRS-R scores at the four-month (difference of 2.98; 95% CI 1.48–4.47, P < 0.001) and six-month (3.38; 95% CI 1.23–5.54, P = 0.003) marks, but no difference in the long term survival data (up to 75 months post treatment, Oh et al., 2018). Both of these trials allowed for participants to be treated with Riluzole.
In 2023, a long-term survival benefit study on 157 people within two years from diagnosis of ALS/MND and treated with Lenzumestrocel showed a higher survival probability when compared to placebo controls from the PROACT database (Nam et al., 2023). This study has a number of limitations and therefore the results from a phase 3 study are necessary to understand Lenzumestrocel’s efficacy in slowing the disease.
More recently, Corestem Chemon ran a phase 3 multicenter, randomized, double-blind, placebo-controlled trial involving 115 people living with ALS/MND (Clinicaltrials.gov ID: NCT01363401) to evaluate the safety and efficacy of Lenzumestrocel further. This study was designed to: 1) assess the long-term impact of two injections (single cycle) of Lenzumestrocel, with Group 1 receiving a single cycle at 26-day intervals 2) evaluate the long-term safety and effectiveness of multiple Lenzumestrocel injections, where Group 2 received the initial cycle followed by three additional injections spaced three months apart. A third group, Group 3 instead received the placebo injections. The primary outcome measures were monitoring of disease progression (as measured by combined assessment of function and survival, CAFS) at 6 months and 12 months as well as long term efficacy and safety evaluation up to 36 months (Nam et al., 2022). The study was run in five centers in South Korea, and, according to the Korea Biomedical Review website, the topline results from this trial showed no difference in disease progression for the groups treated with Lenzumestrocel when compared with placebo.
Dose and Administration
The dosage is 1.0 x 10^6 cells per kilogram of body weight, administered concurrently with Riluzole. The treatment involves intrathecal administration, with two injections given four weeks apart. Each pre-filled syringe contains 4.0 x 10^7 cells in 4 mL. The product should be stored in a cool place, between 2 and 8°C. The expiration date is 48 hours after manufacturing (Corestem Chemon website).
Reported Side Effects
There was no severe adverse drug reaction found during the safety assessment, lasting a year after the first administration.
Current Status
In 2023, a phase 2 study showed that two intrathecal injections of Lenzumestrocel, combined with Riluzole, slowed disease progression compared to placebo. However, given the small size of the trial, Corestem Chemon ran a phase 3 trial to evaluate its long-term safety and efficacy in people living with ALS/MND. The topline results from the Phase 3 clinical trial suggest that Lenzumestrocel may not have a strong clinical benefit. However, no peer review data was published, which makes interpretation of results challenging at this time.
International Alliance of ALS/MND Associations
February 2025
The original language of communication is English and any translation cannot be guaranteed for accuracy of messaging.
SOURCES
Corestem Chemon website – https://corestemchemon.com/eng/business/business__product.html
Oh et al., 2015 – https://pmc.ncbi.nlm.nih.gov/articles/PMC4449093/
Corestem Chemon press release – https://www.nature.com/articles/d43747-020-00727-8
Oh et al., 2018 – https://onlinelibrary.wiley.com/doi/10.1002/ana.25302
Nam et al., 2023 – https://pubmed.ncbi.nlm.nih.gov/37122380/
Nam et al., 2022 – https://pmc.ncbi.nlm.nih.gov/articles/PMC9115933/
Korea Biomedical Review – https://www.koreabiomed.com/news/articleView.html?idxno=26071