What is the cell therapy for ALS called NurOwn? How strong is its potential as a treatment for ALS?
I’ve been following the biotech BrainStorm Cell Therapeutics for many years. Patients keep asking me about NurOwn ALS prospects. They’re looking for hope.
Today’s post is a close look at NurOwn and at BrainStorm as a company. Many of us are now awaiting potential news from BrainStorm related to meeting with the FDA. I write more about the role of the agency FDA later in the post.
What is BrainStorm Cell Therapeutics?
BrainStorm Cell Therapeutics is an Israeli-American biotech company headquartered in New York. They are focused on autologous cell therapy development.
Target diseases include ALS and MS, but they are also interested in others.
Since the pandemic they have also been doing work related to COVID-19.
The President and CEO is Chaim Lebovits.
BrainStorm is most well known for Nurown.
What is NurOwn?
NurOwn is a mesenchymal stromal (stem) cell or MSC-based investigational therapy.
BrainStorm stimulates the MSCs in a proprietary way to secrete neurotrophic factors or NTF. Hence, the drug is sometimes referred to technically also as MSC-NTF.
The MSCs in this case are autologous. For that reason immunosuppression of recipients shouldn’t be needed, which would be a plus.
Proposed NurOwn ALS Mechanisms
The idea behind NurOwn is that the MSCs, once inside the patient, will secrete the NTFs.
These hoped-for “happy factors” will counteract damage from ALS. In this way the drug may slow the progression of ALS. I don’t see that this is a curative approach. Curing ALS would be a much higher hurdle.
However, there is a huge need for effective drugs that even slow ALS. Significantly slowing ALS would be a big win.
What are NTFs or neurotrophic factors?
NTFs are generally growth factors. Some of these factors promote cell survival and hence could stave off neuronal cell death in ALS patients. Specific NTFs that are often mentioned include glial cell line-derived neurotrophic factor (GDNF), neurturin (NRTN), platelet-derived growth factor (PDGF-BB), and cerebral dopamine neurotrophic factor (CDNF). See the cited review paper in the References section. Note that there could be dozens or hundreds of NTFs produced by cells including MSCs. Not all NTFs are necessarily beneficial in general or to ALS.
What data are out this approach? I found six papers specifically mentioning NurOwn. These published studies are pretty diverse. The work includes not only ALS but also MS and autism.
Overall, the data here are mostly fairly early, but one paper from the PubMed search was a randomized Phase II study. It reported that NurOwn was generally safe. The authors argued for hints of efficacy, but that’s not entirely clear.
Importantly, BrainStorm has also completed and published a Phase 3 study on Nurown, which somehow doesn’t show up on PubMed in the above search. The ALS clinical Phase 3 trial failed to meet its primary endpoint relative to an unusually good placebo response.
The firm again here argued for possible indicator of some efficacy, in this case in a predefined subgroup of patients with less severe ALS. How much hope should we take from that? It’s very difficult to say. Oddly, reportedly the firm also corrected an earlier ALS trial paper with a change in a more positive direction.
Some in the ALS community understandably have grabbed onto potentially hopeful statements from BrainStorm.
FDA and BrainStorm
The company has not made much headway with the FDA on NurOwn for ALS, sometimes leading to tension between the FDA and patient groups.
After completion of that generally discouraging Phase III ALS trial, the agency took the unusual step of making a public statement about this ALS work. The FDA explained why and here’s the key passage:
“With the recent completion of a randomized phase 3 controlled clinical trial comparing NurOwn to placebo, it has become clear that data do not support the proposed clinical benefit of this therapy. Data indicated that none of the primary or secondary endpoints were met in the group of patients who were randomized. For the main (primary) endpoint, 27.7% of people given the placebo were scored as responding compared to 32.6% of people given NurOwn. The 4.9% absolute difference in responders was not at all statistically significant, and the small difference between the two groups was most likely due to chance. In addition, there was a modest excess in deaths in those treated with NurOwn, the significance of which is unclear at this time. If BrainStorm plans further studies of NurOwn to determine if the product can provide clinical benefit to individuals with ALS, FDA will continue to provide advice to the company on their development program.”
To sum up, the drug was not effective in this trial. There was also a small blip of excess deaths in the treated group, which raises potential safety issues although it’s unknown if that difference was meaningful.
The ALS Association, which has funded BrainStorm Cell Therapeutics work on ALS, recently raised concerns about potential lack of transparency on Nurown clinical trial data. Here’s a key passage:
“After BrainStorm shared that its Phase 3 trial of NurOwn did not meet its primary or secondary endpoints, we have consistently requested access to the full data package so we could try to better understand its effect on people living with ALS. The amazing testimonials we have seen online do not align with the data that BrainStorm has shared with us or has been published in peer-reviewed publications.”
Looking ahead, everyone is eager to see how the recent BrainStorm meeting with the FDA turns out. Could the agency change course here or at least give some additional bit of hope? BrainStorm Cell Therapeutics stock is way up the last couple of weeks, but that may not mean anything.
In the bigger picture, the idea of approaching ALS with cell or regenerative therapy of other kinds still has promise.
I’ve been writing about this long enough to remember the Neuralstem cell therapy work for ALS, which got hyped and gave people false hope. That kind of thing needs to be avoided.
At the same time, the ALS community needs options and lengthy periods of waiting are extremely difficult with a fatal illness like this.
Knowing more about the causes of ALS will also help this overall area of translational and clinical research.