NurOwn stem cell phase 3 study

[KarenNWendyn]

Cherise,

Is your dad age 60 or younger? If over 60, he wouldn’t qualify for the study.

In terms of whether it’s worth going off Radicava to qualify for the NurOwn trial, that’s an individual decision. There is a good long thread in the general forum concerning people’s experiences with Radicava.

The NurOwn is not available in Israel. That was only for a phase 2 trial, which has been completed. The treatment has not been released yet. That may or may not occur depending on the results of the current phase 3 trial. Jethro from Croatia looked into trying to get it from Israel and was told that’s not available.

 

[jaclyn]

Can someone much smarter than me explain what the trial results are saying right now?

Is it possible for a couple people to report great improvement and the drug to still fail? This is way above my paygrade.

 

[Nikki J]

Yes. It has happened more than once that a drug looked promising and failed their phase 3. Everyone had great hope for Dex in 2012. Phase 2 looked good phase 3 people were saying positive things. There was an expanded access program. Plans for an open label extension were in effect along with a push for fast fda approval. It failed in the larger group.

Because all PALS are differebt and because reversals and plateaus do happen ( Dr Bedlack wrote a paper on this) it is hard to know whether a treatment worked for someone or if some other factor had an effect

There are anecdotal reports of improvement by persons in the current trial. We can’t even know for sure they got the treatment and not placebo. I believe phase 2 showed some improvement in some participants but it did not last and it wasn’t everyone I am not sure it was even statistically significant.

 

[KarenNWendyn]

Published results are often tricky to interpret. You’d think it would be more black and white, that is a study would either show if a treatment worked or not.

Unfortunately, it’s not so black and white.

Sometimes studies only look at a small selected group of patients who may not be representative of the majority of patients with a given condition. In the case of NurOwn, the study didn’t look at patients who were slow progressors. In the Edaravone trials, the study looking at all patients with ALS didn’t show a benefit; only a selected small subgroup benefitted.

Laurie also mentions the phenomenon known as “regression of the mean”. This means that most conditions ebb and flow in terms of disease activity. In ALS, one experiences periods of slow progression, rapid progression, and even plateaus. Occasional people may even have apparent brief episodes of improvement.

So when there is an intervention, sometimes an apparent benefit may actually reflect a slow-down of disease progression or an improvement that would have happened anyway. It’s so hard to tell. That’s why trials need to be done on large groups of people with matched controls, and then verified by subsequent studies.

The main purpose of a phase 2 study is to demonstrate safety, to compare different doses or routes of administration, and to see if there is a suggestion of benefit from the treatment. Studies that show safety and efficacy then go to a phase 3 trial looking at a much larger group of patients with matched placebo controls. It’s always important to read carefully to see what kind of patients were excluded.

 

[jaclyn]

So based on the results we have seen now, are you both not really optimistic that this is the important drug we have all been waiting for? Or is it still too early to really get any hard sense?

This biotech journalist seems to think that Nurown is a fail:
https://www.statnews.com/2018/06/26...m-right-to-try-law-following-heavy-criticism/

 

[lgelb]

Jaclyn, I hope PALS are not awaiting one magic "important drug," because it's unlikely that one treatment will significantly improve the prognosis of all PALS. It is a syndrome, really, because there are different onset sites, not everyone ends up with problems in every region, etc. The discrepancies seen across subscales of the ALSFRS-R (warts and all) with all the pipeline treatments speaks to that heterogeneity.

I renew my statement that right now, more can be achieved with quantity and quality of life with non-drug modalities like passive ROM exercise, diet, BiPAP, hospital bed, etc. than any drug currently on the market, from what the data have said so far. So while you wait for whatever shows up, this is the time to do the best you can with everything that you do control.

IMHO, it is too soon to tell with NurOwn what the "best case" patient and "worst case" patient will look like, because the dosing regimen being tested in Phase III hasn't been tried yet. While there could be greater efficacy than we have seen as yet, there could also be more safety issues. The unknowns include what % of PALS (across all progression groups) will have any response, what % will have a life-changing response, what % will be worse off, etc. And that will also rest on how early/how late it's started, and in whom.

Best,
Laurie

 

[KarenNWendyn]

I completely agree with Laurie.

We can’t get too excited about therapies from a phase 2 trial, and there are no miracle cures. I never would have participated in Right to Try with NurOwn based on phase 2 data.

However, the phase 3 trial of NurOwn should give interesting results, one way or another.

Even if it is shown to be superior to placebo in phase 3, it is still not a cure.

The company (and the insurance companies) will still need to figure out how often transplantations with NurOwn will need to occur to prevent further clinical deterioration, and if subsequent treatments are equally beneficial (or perhaps more, or less beneficial) than the initial treatment.

There are so many questions that will still need to be answered even if the outcome of the phase 3 trial is promising.

 

[Cherise77]

Thanks KarenNWendyn! My Dad turned 59 this year so he still qualifies as of now. I’m communicating with the coordinator on the trial in San fransisco.
We have an appt with our ALS clinic on July 11th to meet with the Neurologist and get her opinion on the trial.
These are such hard decisions to make. There are a few trials going on now but are any of them worth the risk of possibly getting a placebo and holding off on other treatments?

 

[oya99]

Here is some recent news (07/02/2018 ):
"In partnering with Dana-Farber for the manufacturing of NurOwn, BrainStorm has secured an additional facility to enhance production for the ongoing pivotal Phase 3 clinical trial, and to support manufacturing capacity for additional clinical indications.
BrainStorm is also pleased to update that CMC activities at City of Hope and enrollment in all six U.S. clinical sites are proceeding well. The first meeting of the Phase 3 Data and Safety Monitoring Board (DSMB) is expected by the end of August 2018 and Brainstorm will provide an update thereafter."

Brainstorm's CMO is slated to meet with a number of top hospitals/neurologists in NY in the coming weeks.
It is still too early to predict if these are indications of possible good results in Phase 3 trials or "window dressing" for investors.

 

[Par220]

Although I am still disappointed about the RTT failure, I wanted to post what the CEO wrote on twitter today:

C Lebovits
@Cylebo
‏
Manufacturing is proceeding as and even better then planned. We had a good surprise that pre estimated screening failures were wrong!! we are performing better then the most liberal estimates.
Due to tough inclusion exclusion criteria's experts pre estimated ~50% "screening failures". But happily it's less then 10%! a good problem to have. We now face OVER enrollment. As an outcome few patients(3-4)have a delay. We added capacity. Dana Farber will be active very soon!

 

[Cherise77]

Yes, that’s what my Dad and I have been told today too.

The clinical research nurse at the California Pacific Medical Center emailed to advise that the trial is on a screening hold for 1-3 months. The process to producing stem cells is backed up several months.

Waiting to have a call with her on Wednesday. I’ll advise if I get any further information.

 

[GregK]

Although I am still disappointed about the RTT failure,..

Calling Brainstorm's decision to not participate a 'failure' is inaccurate.

Funding was always recognized as a issue.

 

[rknt50a]

I find the production delay completely incongruous with a company that was telling us that RTT might be a possibility just days ago.

My understanding is that there are people who are already in that screening phase who are stuck in a delay. That is poor planning on Brainstorm's part imo.

It will be interesting to see how this story goes on. I feel bad for the trial volunteers.

 

[lgelb]

The earnings call today mentioned the trial and some milestones, as well as other indications in discussion with the FDA.

 

[jethro]

I have info from a person phase III trial. Obviously placebo. He is worse significantly, but it doesnt mean 100% that he's on placebo.
BUT
Brainstorm have info...
What does it mean: THEY GRANTED PATENT IN EU AND JAPAN? Why should anybody patent invention if it is not sure that it works and can not make profit of it? it is not cheap. Are they sure right now that they will be able to sell licence to apply nurown? is it gambling? deal with fda? small but secure als retardant, just like radicava is? stem cells are mighty weapon. if it works, it is impossible that it affects just neurons. i think it is kind of rejuvenation of whole organism. brainstorm can not extract effects of nurown. if they could, they do more patents.
strongly believe if it works, it affects some zones they couldnt predict.
Should we read something between a lines?