dm+d

Unassigned

New Medicines

NurOwnAmyotrophic lateral sclerosis (motor neurone disease)

Information

NurOwn
New molecular entity
BrainStorm Cell Therapeutics
BrainStorm Cell Therapeutics

Development and Regulatory status

None
None
Phase III Clinical Trials
Yes
Yes
Feb 21BrainStorm Cell announces it recently met with the FDA and received feedback on a high-level data summary from the NurOwn ALS PIII trial. The FDA concluded from their initial review that the current level of clinical data does not provide the threshold of substantial evidence that FDA is seeking to support a Biologics License Application (BLA). In addition, the FDA advised that this recommendation does not preclude Brainstorm from proceeding with a BLA submission. Brainstorm plans to consult with principal investigators, ALS experts, expert statisticians, regulatory advisors, and ALS advocacy groups to assess the benefit/risk of a BLA submission before making a final decision. It states that many with longstanding experience in ALS therapy development agree that there was evidence of benefit from NurOwn cell therapy and hope that there will be an opportunity for further assessment in ALS [10].
Nov 20The company have stated that the FDA will review the PIII data (which did not meet primary outcome measure vs. placebo) to see if there is a path forward to support approval. [8]
Feb 20In its latest annual report, Brainstorm expects the pivotal PIII trial to support the FDA BLA filing of NurOwn® for ALS in Q4 20. The company met with the FDA on Feb 11, 2020, who confirmed that the fully enrolled trial is collecting relevant data critical to the assessment of NurOwn efficacy. The FDA indicated that they will look at the totality of the evidence in the expected PIII trial data. Furthermore, based on their detailed data assessment, they are committed to work collaboratively with BrainStorm to identify a regulatory pathway forward, including opportunities to expedite statistical review of data from the PIII trial. Plans for applying for an EU licence not stated. However, BrainStorm does state that, once fully developed, it intends to market NurOwn® for autologous transplantation in patients by neurosurgeons in medical facilities in the U.S., Europe, Japan and Israel [6].
Oct 14Granted fast track designation in the US for ALS.[2]
Jan 13NurOwn® received ATMP designation by the EMA´s Committee for Advanced Therapies in January 2013.[2]

Category

Autologous bone marrow-derived mesenchymal stem cells (MSC) - stimulated to differentiate into astrocyte-resembling cells expressing astrocytic markers and neurotrophic factors, such as GDNF, BDNF, VEGF and HGF, to replace and/or protect existing cells
MND is relatively uncommon with an annual incidence of about 2 cases per 100,000 population. Prevalence is about 5-7 per 100,000. General practitioners can expect to see one or two cases in their career [1].
Amyotrophic lateral sclerosis (motor neurone disease)
Intramuscular and
Intrathecal

Trial or other data

Dec 21BrainStorm Cell presents new analysis of the PIII ALS trial that evaluated treatment effects of NurOwn on CSF biomarkers and the relationship between these biomarkers and clinical outcomes. In the trial, CSF samples were obtained prior to the first treatment and at 6 additional time points. Statistically significant CSF biomarker changes from baseline were observed with NurOwn treatment vs. placebo, particularly in biomarkers related to neuroinflammation, neurodegeneration, and neurotrophic factors. Prespecified statistical modeling utilising machine learning identified biomarkers that are predictive of the treatment response to NurOwn with high accuracy (>80%). Markers of neuroinflammation, neurodegeneration and neuroprotection were all selected in the final model, suggesting that NurOwn´s biological activity across multiple disease pathways could prove important to impacting progression of ALS disease. These results provide additional evidence linking the mechanism of action to NurOwn impact on ALS progression (Phase 3 primary endpoint). BrainStorm Cell wants to understand the effects that longer term treatment with NurOwn could drive in biomarkers of neuroinflammation, neurodegeneration and neuroprotection and ultimately the effect on clinical outcomes through its Expanded Access Program [11].
Mar 21Data from 28 week PII trial reported which showed that 38% of pts treated with NurOwn showed >10-point improvement in the MS Walking Scale (MSWS), 47% showed an 8-letter improvement in the low contrast letter visual acuity test (LCLA) and 67% showed >3-point improvement in the symbol digit modality test (SDMT), a measure of cognitive processing.[9]
Nov 20Data from PIII trial of NurOwn® (MSC-NTF cells) for ALS did not find a statistically significant difference between the therapy and placebo for improving scores on a revised ALS functional rating scale (ALSFRS-R). The mean change from baseline to week 28 in the ALSFRS-R total score was -1.77 and -3.78 with NurOwn and placebo, respectively (p=0.198).[8]
Jun 20Top-line data are still expected from the PIII pivotal trial investigating NurOwn® in ALS by Q4-2020. Despite challenges presented by COVID-19, pt dosing is on track and the ALSFRS-R rating scale has been validated for telephonic administration. All pts have received at least 2 treatments of NurOwn®.[7]
Apr 20No update to clinical trial registry entry for pivotal PIII (NCT03280056) study. In Oct 19, the expected date for collection of primary outcome data was Oct 20 [4].
Nov 19Data from randomised, placebo-controlled, PII trial (NCT02017912) to determine the safety and efficacy of a single transplantation of autologous bone-marrow derived MSC-NTF cells (NurOwn) in 48 pts in the US with ALS announced. Pts were randomided 3:1 (treatment: placebo) and, after a 3-month pre-transplant run-in period, received a dose of MSC-NTF cells (n=36) or placebo (n=12) and were followed for 6-months. A single transplantation of MSC-NTF (NurOwn) cells was safe and well-tolerated. The rate of ALS disease progression (ALSFRS-R slope) was stabilised for up to 12-16 weeks in a pre-specified group of pts with rapid progression (p<0.05). A higher proportion of MSC-NTF treated study participants experienced ≥1.5 point/month improvement in ALSFRS-R slope at all post-treatment time points (statistically significant at 4 and 12 weeks post-transplantation (p=0.004 and 0.046, respectively). CSF neurotrophic factors increased and inflammatory biomarkers decreased 2 weeks post-transplantation (p<0.05) CSF MCP-1 levels (a marker of microglial activation and neuroinflammation) significantly decreased post-transplantation and correlated with ALSFRS-R slope improvement at all time points (p<0.05). Data are published in Neurology:Volume 93, Number 24. [3,5]
Oct 19Pivotal PIII trial (NCT03280056) enrolled 261 pts in the US.[2,4]
Aug 17Pivotal randomised double-blind trial PIII trial initiated which will evaluate safety and efficacy of NurOwn® given by IM and Intrathecal injections (Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors) in pts with ALS (NCT03280056). Primary outcome measure will be the ALSFR-S score responder analysis.[2]
Dec 13PII randomized, double blind, placebo controlled multicenter trial (NCT02017912) of Autologous MSC-NTF Cells in Patients With ALS (NurOwn) initiated.[5]