Sorry about the spelling errors. The above should read: "Notice that there is NO mention of "placebo" anywhere?"
Also "In my view", not "On my view".
It's hard to do this from my iPhone :)
One last thing just to be clear. The double blind, placebo controlled data from BCLI that I am referring to is the Phase 2 data to be announced in 2016, not this upcoming Phase 2a data.
Another big reason why I think BCLI will have the edge over CUR in the long run, is because of their Phase 2 trial design. Here is the official title of CUR's Phase 2 trial:
"A Phase II, Open-label, Dose Escalation and Safety Study of Human Spinal Cord Derived Neural Stem Cell Transplantation for the Treatment of Amyotrophic Lateral Sclerosis"
Notice that there is mention of "placebo controlled" anywhere? Compare that to BCLI's trial title:
"A Phase 2, Randomized, Double Blind, Placebo Controlled Multicenter Study to Evaluate Safety and Efficacy of Transplantation of Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors (MSC-NTF) in Patients With ALS"
Not only is it "placebo controlled", but double blind. On my view, BCLI's Phase 2 trial is designed far better than CUR's. Even though CUR is further along in Phase 2 (finished enrollment) BCLI will be presenting stronger and more critical data. Not having a placebo controlled arm in their Phase 2 data weakens CUR's data substantially in my opinion. When you factor that in with BCLI's superior delivery method and current undervalued market cap, that is why I take my chances with BCLI.
I think there are a lot of factors in trying to determine who is leading the race for an ALS treatment. Of course safety and tolerability are most important. Then you obviously have efficacy, knowing how well the treatment works. Then there is the phase of study they are in. Then finally the delivery method.
In my opinion, BCLI is ahead of the competition (CUR and Genervon) in 90% of these areas. They have a stellar safety and tolerability profile on a similar amount of patients as CUR. However CUR's delivery procedure is very complicated and higher risk as it entails opening up a patients spine and inserting a scaffolding. BCLI's is a simple injection outpatient procedure. Genervon's delivery system is a pill which is very simple, but they need to show data on more than 8 patients before anyone can conclude anything about safety and tolerability. That goes for efficacy as well. So I don't think Genervon can even be considered in the same conversation at this point.
First off let me be clear. I am not a scientist nor am I any kind of financial/stock expert (that is probably pretty obvious in my posts). I am a laymen investor who reads the data and tries to make sense of it just like anyone else.
To answer your question, to my understanding, companies have the freedom to structure a trial the way they want, as long as it meets FDA criteria and fits their protocol. It is common for the FDA to let a company do a small pilot study (one-tailed) just to simply prove a hypothesis. I think your assessment is correct. The next step in my opinion will likely be the FDA asking Genervon to conduct a well-controlled Phase 2b study (which would of course be two-tailed).
The data BCLI will be presenting is two-tailed. It is not a pilot study and they certainly would not be trying to publish one-tailed data from a pilot study in a peer reviewed journal (among other obvious items). What BCLI won't have in the upcoming data is a placebo arm. That is unfortunate, because most scientists want to see how a treatment responds compared to placebo. I am glad that they have added a placebo arm in the new Phase 2 trial in the US. The upcoming Phase 1/2/2a data will still be important though, and since they measured patients 3 months prior, we'll still be able to see how they reacted after treatment. However, as I said, many will want to see it compared to placebo, and that is why I think the most important data to the scientific community will be the Phase 2 data reported in 2016.
Also, I am not really sold on this author knowing exactly what he is talking about. With comments like these:
"A successful ALS drug must show effects over a year or more so that short term results must be viewed with caution."
Where is he getting that? That is not true. So far the data on NurOwn suggests that the effects wear off after about 3 months or so, so they'll need to re-dose 3 or 4 times a year. That doesn't mean it isn't successful.
"Recently there have been two large trials in ALS involving Biogen’s dexpramipexole and Cytokinetic’s tirasemtiv. Neither drug was successful in showing a statistically significant improvement in ALSFRS-r in large randomized trials involving several hundred patients. [b]Hence a statistically significant improvement in a 12 patient randomized trial would be stunning."
I think this is a meaningless statement. It wouldn't be stunning if the drug actually worked. Biogen and Cytokinetic's drug failed because it just didn't work. Especially if you are working with stem cells like BCLI and CUR, where you can't tell the cells not to do their job from the beginning.
I do agree with the points about not showing placebo results and that making this data difficult to interpret clearly. Why have a placebo arm if you aren't going to compare those who were treated with it? It brings the entirety of the data into question in my opinion.
The SA article was based on the PR that went out, so I am not sure why the author keeps blaming SA. Here is the most important bit from this new article:
"Unfortunately, the reported improvement in ALSFRS-r is misleading. The results for the eight patients treated were not compared to the four patients on placebo. Apparently, the four placebo patients did as well or better or only slightly worse on the ALSFRS-r scale than the eight patients on GM640. Faced with this disappointing result, Genervon decided to compare GM604 to historical results that were observed in ALS patients treated with placebo in other clinical trials. Here it found a difference. There are lots of issues in choosing to look at historical results as placebo patient results can differ from study to study depending on patient characteristics. It is possible to pick and choose results that one is looking for. My interpretation of the ALSFRS-r data, and one that I think almost anyone else would reach, is that there is no difference between GM604 and placebo in this trial based on the results shown in this study."
More good news out for NRIFF. Especially like the last sentence in this paragraph:
MISSISSAUGA, ON, Oct. 22, 2014 /PRNewswire/ - Nuvo Research Inc. (TSX:NRI), a specialty pharmaceutical company with a diverse portfolio of topical and immunology products, today announced the results of a market study commissioned to investigate the U.S. opportunity for the Company's experimental immunotherapy product, WF10, as a treatment for patients with refractory allergic rhinitis. The study, performed by Psscion Lifesciences Consulting (Psscion), forecasts that WF10 could capture 10-15% of the U.S. refractory allergic rhinitis market with peak U.S. annual sales of US$0.7 billion to US$1.1 billion.
And what do these quotes from Fiorino in the interview (which is all I am interested in) have to do with AF?
Hey look who it is, golf.paul123, the troll from the BCLI board. How is that multiple personality disorder treating you?
Genervon's goal was to prove that there is a positive effect in one direction from their treatment. After checking the clinicaltrials site I confirmed this as it is indeed just a "pilot trial":
"GM604 Phase 2a Randomized Double-blind Placebo Controlled Pilot Trial in Amyotrophic Lateral Disease (ALS)(GALS)". (Description of the trial)
"1. This pilot trial is designed to test proof of principle, i.e. determine if a 2-week IV bolus treatment with this agent can (1) change ALS protein expression (target biomarkers and efficacy biomarkers) after treatment (2) have preliminary effects measures of ALS disease clinical progression."
What is a pilot trial? (from aha journals):
"Pilot trials are exploratory studies limited in size and scope that give insight into the actions, efficacy, and safety of a drug or device, but cannot provide definitive support for specific mechanists or therapeutic claims."
So to make a long story short, Genervon's trial seems to be a one-tailed pilot study that is only measuring one direction and cannot really be used to fairly and accurately measure statistical significance or make therapeutic claims. Of course that is fine as it is just a pilot study, but I am not sure how I feel about the way they touted the results.
Again, any feedback or corrections if I am wrong in my analysis of this would be appreciated.
First, I noticed something interesting from the PR yesterday. They said the following under the PD Clinical Data:
"2.) Changes in 4 out of the 8 secondary clinical outcome measures (UPDRS ADL, Schwab & England, Hoehn & Yahr and MOCA) at week 2 (visit 6) were statistically significant at the one-tailed 10% level."
A one-tailed study would only be measuring one direction of the data and would greatly inflate the data numbers. Of course BCLI and CUR are doing two-tailed studies, measuring both directions of the effect of the treatment. Presenting one-tailed data to the FDA would almost certainly result in the FDA saying "great now do it again in a two-tailed study".
Here is an excerpt from a paper done at UCLA explaining the difference between one-tailed and two-tailed studies:
"When is a one-tailed test NOT appropriate?
Choosing a one-tailed test for the sole purpose of attaining significance is not appropriate. Choosing a one-tailed test after running a two-tailed test that failed to reject the null hypothesis is not appropriate, no matter how "close" to significant the two-tailed test was. Using statistical tests inappropriately can lead to invalid results that are not replicable and highly questionable--a steep price to pay for a significance star in your results table!"
I did some digging into Genervon's data and found some important things that I think clearly change the strength of their data and it was interpreted by the market.
Here is the cliff's notes version. I'll try to post a more detailed version in a bit:
The Genervon ALS Phase 2a trial was a simple pilot study which seems to have been done as a "one-tailed" study. They mentioned "one-tailed" in the PR and most pilot studies, where they are simply just trying to test a hypothesis, are one-tailed. One-tailed trial data will have greatly inflated numbers as it is only measuring one direction of the effect of treatment. Where as a two-tailed trial (what BCLI and CUR are doing) measures both directions and therefore the numbers are lower.
I think it is pretty clear that this is the case with Genervon's trial data, but would of course appreciate anyone to look at it my "analysis" which I'll try and post below, and punch holes in it.
Good news for anyone interested in this stock. NRIFF sold their U.S. rights to Pennsaid 2% for $45M. After receiving $10M from the lawsuit settlement with MNK, NRIFF now has $67M in cash. With a $48M market cap they have more cash per share than price per share. Very low burn rate at about $2.5M a quarter and a major catalyst upcoming with the release of final Phase 2a data for their WF10 trial in Q1 2015.
WF10 is for the treatment of rhinitis and has showed far superior results compared to the current forms of treatment.
Derp! Good one! I should go round up some of your "best" posts from the ONCS board and paste them here so that everyone can see how pathetic you are and that you have no clue what you are doing.
This one was off our radar because it isn't a publicly traded company. BCLI's interim Phase IIa results were also very good. The ALSFRS-R score of p=0.035 is the only thing we really know of their interim data. Other than that 63% of the 10 patients (out of 14) whose data was analyzed showed halting or signs of improvement. And then you have to take into account that 29% of BCLI's patients showed stabilization in the 3 months prior to treatment, so I believe that waters down the data numbers a bit. We'll just have to sit and wait until BCLI releases top-line data. But this hardly spells the end of BCLI.
This definitely good data though and something to keep an eye on if you are a BCLI/CUR investor. Very good news for ALS sufferers.
Looks like they let the troll out of his cage again. What's funny is seeing how much of an amateur idiot he is on the ONCS board. He has no idea what he is doing and thinks that being a trolling actually has an effect on the pps.
One thing for sure is that with 10 weeks left in the year and 5 milestones waiting to be announced, it is going to happen soon and in a flurry.