Neurotrophic factor-producing mesenchymal stem cell therapy

Unassigned

New Medicines

NurOwn · Amyotrophic lateral sclerosis (motor neurone disease)

Information

NurOwn
Advanced therapy medicinal product (ATMP)
BrainStorm Cell Therapeutics
BrainStorm Cell Therapeutics

Development and Regulatory status

None
None
Phase II Clinical Trials
Yes
Yes
Feb 20 · In 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 14 · Granted fast track designation in the US for ALS.[2]
Jan 13 · NurOwn® 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

Jun 20 · Top-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 20 · No 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 19 · Data 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 19 · Pivotal PIII trial (NCT03280056) enrolled 261 pts in the US.[2,4]
Aug 17 · Pivotal 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 13 · PII randomized, double blind, placebo controlled multicenter trial (NCT02017912) of Autologous MSC-NTF Cells in Patients With ALS (NurOwn) initiated.[5]