Phase 2 ALS trial of Neuralstem's NSI-566 meets safety endpoints and shows 47% response rate

• A 15-patient Phase 2 clinical trial evaluating Neuralstem's (CUR) Orphan Drug-designated spinal cord-derived neural stem cells, NSI-566. for the treatment of amyotrophic lateral sclerosis (ALS) met its primary safety endpoints. The maximum tolerated dose of 16M transplanted cells and the surgery were well tolerated. Only one patient experienced a surgical serious adverse event.
• The therapy involves transplanting NSI-566 cells directly into specific segments of the spinal cord where the cells integrate into the host motor neurons. Patients received up to 16M cells in 40 injections, which investigators believe is the maximum tolerated dose.
• Secondary efficacy endpoints nine months after surgery show a 47% response rate (n=7/15) as measured by either near-zero slope of decline or positive slope of Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) score and by either a near-zero slope of decline or improvement in grip strength. ALSFRS is a standard clinical test used to assess ALS patients.
• The average ALSFRS score for responders was 37 compared to an average score of 14 for non-responders. The responders retained 93% of their baseline score versus 35% for the non-responders. The difference was statistically significant. The average slope of decline for the responders was -0.007 point per day versus -0.1 point per day for non-responders. The difference was also statistically significant.
• The complete data is being compiled into a manuscript for publication. A larger trial is expected to start this summer.
• CUR is up 12% premarket on higher-than-normal volume.

Comments

[Pequod]

I am not an expert but did a simple comparison to another study and would like feedback from others. Of coarse it sounds like they gave different amounts to different patients here but overall the loss of ALSFRS was almost as if nobody had been given any injections.

Here is how I arrived at this-

I used the graph on the Brainstorm study where patients start out with a reading of 40 and take 28 months to go to 0. That computes to a loss of -0.05 per day in ALSFRS score.

From the study they have here the loss was -

responders -0.007 per day
non-responders -0.1 per day.

Notice the -.1 per day for non responders. If you multiply that out to one year you get a loss of 36.5 points, or almost near death (.1 x 365). That is a very rapid loss and from what I read is much faster than the average.

However let's go back to the other responders and add those in-

What is the average loss per day with both combined?

(.007 x 7) + (.1 x 8) and divide this by 15 patients we get a loss average of .06 per day. That is almost the statistical average loss for ALS assuming we use the loss as going from 40 to zero in 28 months.

Since this was not a full amount of patients it could be my analysis is wrong and they will be statistically significant. However one does have to account for the 8 patients that seemed to have a much higher loss of ALSFRS score than average. For the study to show statistical improvement the non-responders should have an average loss compatible to all the ALS patients outside the study.

BTW if you do a google search for "Figure 1: ALS disease progression is highly variable among patients." you can see some patients live for quite a long time too. It may be very difficult to even come up with a statistical number.

[Charles Griffiths]

Also not an expert but with 15 subjects in 9 months, I would expect 1-2 deaths. With no control, the placebo effect could be keeping them alive.

[Bio Bull]

Placebo effect? All 15 patients received the actual treatment. To be clear, there were no sham surgeries.

It's funny watching people struggle to interpret the trial when they clearly weren't paying attention to it for the past year. Like P1, this was a safety trial. Yes, 7 of 15 patients did great under the treatment - that's an amazing bonus but this wasn't to determine efficacy. P1 had a similar bonus. I think you look for efficacy whenever the final trial, which identifies the optimal patient to treat, begins and which may even have a control group.

[Charles Griffiths]

Placebo effect. "The placebo effect can make some treatments seem like they help certain symptoms, when in fact they do nothing to directly cause a change in the disease."

from http://bit.ly/1HVnnzs

Hope that helps.

[BucephalusCa]

It seems the main concern or criticism about the results is that approx. half of the subject (53%) declined. The comment I read suggested that the rate of decline in this group of "non-responders" may be greater than the decline that would have occurred without the Neuralstem injections. Can anyone verify if this is true? I don't fault Neuralstem's Phase II for having "no control group" (since the universe of untreated ALS sufferers are the control group), but I would like to know if the non-responders declined at a greater rate than the non-treaters. I remain a bull either way (based on the 47% responders - hallelujah!) but nonetheless want to know.

[candooman]

Bause, As pointed out in the numbers stated in the article, the slope of decline of the responders is almost flat (their condition did not worsen) whereas the slope of decline for the non-responders was significantly lower -- their health got worse...... just like those who have the decease......(I cannot use the word treated because there is no treatment).

[Bio Bull]

What's amazing to me is that data like this, IMO, would get this treatment approved. Market valuation should increase. The only thing I see today are a ton of people who misunderstood the nature of the Phase 2 and ignored the great scores for the non-responders.

[stockdunn]

Perhaps investors have been spoiled by the very high success rate of Gilead's Harvoni against Hepatitis C. But it took a long time to achieve those results, and I don't believe GILD was trading at $100~/share at the same stage CUR is now.

[Neurology]

The market reaction makes no sense. This looks like great news. I am not a neuromuscular (ALS) specialist but I fail to see why CUR isn't + 20% or more.

[Len Friedman]

CUR is largely down because it is not a meaningful, living presence in the lives of ALL traders. While I'm not about to disparage them, they and I do not share concerns. For them it's a matter of finding vehicles most likely to bring in profits. For many of us, myself included, financial gains are secondary.

Not wishing to sound judgmental, I'm 74, healthy and with a great life, thanks to a wonderful wife and a history of profitable trading. Gains resulting from CUR's success will benefit those not yet afflicted, perhaps, as well as those set up on the receiving end of our charitable trust. However, funds we've placed into Neuralstem---one way or another---will likely be of benefit to this company of ours aiming to relieve some of the pressures suffered by fellow humans.

Each of us can devour no more than his/her tolerable limits, be it food, monetary wealth, or riches of all common sorts. Who says we can't dream the dream of those caught in an anguished quagmire of pain and disappointment? It is for this last remark that I believe the market pricing mechanism finds itself in a swoon.

[Vet67to82]

I discovered Neuralstem (CUR) a long time ago while searching the web for understanding, and potential treatment, of debilitating nerve damage I sustained in an accident. I remember one doctor, and now YEARS of MORE doctors with the SAME spiel, running thru the list of everything I can never do again, should never attempt to do again, telling me most patients, with my injuries, give up ... struggling to do little more than just existing, and taking up space, long before getting to the point I am at.

I am not looking for sympathy. I want my fingers and left arm to stop atrophying. I want the pain to permanently cease and desist. I would so much like Neuralstem to succeed so that I might again skydive, climb mountains, rappel, run the rapids, or slide into the front seat of a jet trainer ... pull a wing over, barrel roll, loop and maybe even an outside loop. Of course I'd also like to perform everyday tasks like not having to struggle to put on and button a shirt. I want MY QUALITY of life back. I haven't given up.

So, you see, for those of us injured, or afflicted, the HUGE point Mr. & MS. Fickle Market doesn't get, Neuralstem's (CUR) success or failure is NOT about the money ... for us , it is seeking to go beyond merely existing, it is about living, participating, and contributing.

[B52beemer]

Poor, poor Lenny Friedman. So old and yet you have so much to learn.

[Vet67to82]

Great news: Neuralstem ( CUR ) has received orphan designation by the FDA for NSI-566 in ALS.

The FDA has this to say about "orphan" status approvals here:

http://1.usa.gov/1g8JC6G

" Designating an Orphan Product: Drugs and Biological Products

The Orphan Drug Act (ODA) provides for granting special status to a drug or biological product (“drug”) to treat a rare disease or condition upon request of a sponsor. This status is referred to as orphan designation (or sometimes “orphan status”). For a drug to qualify for orphan designation both the drug and the disease or condition must meet certain criteria specified in the ODA and FDA’s implementing regulations at 21 CFR Part 316. Orphan designation qualifies the sponsor of the drug for various development incentives of the ODA, including tax credits for qualified clinical testing. A marketing application for a prescription drug product that has received orphan designation is not subject to a prescription drug user fee unless the application includes an indication for other than the rare disease or condition for which the drug was designated.

A sponsor seeking orphan designation for a drug must submit a request for designation to OOPD with the information required in 21 CFR 316.20 and 316.21. Each designation request must stand on its own merit. Sponsors requesting designation of the same drug for the same rare disease or condition as a previously designated product must submit their own data and information in support of their designation request. The granting of an orphan designation request does not alter the standard regulatory requirements and process for obtaining marketing approval. Safety and effectiveness of a drug must be established through adequate and well-controlled studies. "

... and the expanded trial should produce MORE people helped followed by demand for that help!

It is not just the extension of life in a miserable condition to the inevitable ALS end, it is about improving QUALITY of life while also extending life ...

[gambl3r]

More than 20 percent down, seriously what is wrong with people.

[BDA_Lemming]

No doubt it's the 47% number that has got people spooked.

[T-time]

So why is it now down 5% Premarket???

[Bio Bull]

I think it's mostly traders and perhaps a short attack led by comments from you know who. Bottom line is that 7 of 15 either maintained or improved (results at a high level). Details coming soon in publication as they noted.

[BRENNZN]

Yes Bio Bull; the initial study was clouded (obscured) with illogicalness of hope (qualitative).

Slow death of ALS.

[Bio Bull]

Excellent news! Many were wondering if the P1 results were simply lucky or whether there is an actual treatment here. I feel better now knowing that 7 of 15 had such an excellent response. In addition, they think they can further target the ideal patient as they plan the next trial which is an interesting bonus here. Look forward to detailed published results.