"Secondary endpoint: Statistically significant improvement in a measure of executive function(cognition) in research participants administered 250mg PBT2 daily (p=0.042).
PBT2 250mg was also associated with a favourable signal in functional capacity.
Preliminary evidence suggests PBT2 250mg reduced atrophy of brain tissue in areas affected in Huntington disease, seen in a pilot imaging sub-study.
Company plans to advance PBT2 to a confirmatory Phase 3 clinical trial.
Prana to host investor conference call and webcast today at 5:30pm ET; "
We do not know what the control SOC -- PFS and OS -- time was from IMUC's phase II trial. This will be helpful information. I think we might learn it at the conference call today. I think it might be 9 months with all the latest advances, but I'll wait to see.
Others might disagree, but I'm simply going to say that I believe the 33 patients from 2008 in the DCVAX-L study were all in the treatment arm. I also believe they are part of the 312 phase 3 study. Had ICT-107 simply had a small percentage of "long-tail" patients from 5 years ago, like NWBO has, in IMUC's phase 2 mix when the results came out yesterday, their stock would be at 20. When IMUC "long-tail" data does get a chance to mature, it will move IMUC into complete statistical significance across all metrics. My estimate would be IMUC could reach complete statistical significance as early as the 2nd quarter next year.
Over many years, Linda Powers repeatedly emphasized the "long-tail" DCVAX-L has. All their people know this. There are so many advantages to having those 33 patients from 2008 included in this phase 3 study, that I will not go into them in this simple post.
Then Adam tried to destroy the scientist who helped invent the stock's medical treatment called PBT2. Instead, the planet cheered for said scientist who found a way to help treat Huntington's patients -- when no one else could.
Slightly complicated answer. You are no doubt waiting for the specific enrollment history.
The trial actually began in 2007 and paused in 2008 to convert it to a placebo trial.
When it started back up in January 2011, it kept 33 treated (not placebo) patients from original start date. These people had been on DCVAX-l for over 24 months by then.
Once it started back up in 2011, it has averaged somewhere between 20-22 patients a quarter. The problem most people have is that is an average, enrollment accelerated over time, so I can't tell you for instance, how many were enrolled by December 2012.
Let's just use their information as a steady enrollment to do some math.
Really start counting quarters in 2q 2011 (plus the 33 from 2008):
6 quarters x 22 = 132 patients + 33 patients = 165 patients.
55 of those patients would be control arm patients. They would have all had tumor regression by now.
That means you only need 11 from the treatment group starting as far back as 2008 to get to 66. But it took us a very long time to get there -- even with 33 original patients in the treatment arm since 2008. This is likely very good news.
The Math 'geeks' will now pray Linda gives some concrete enrollment number history so they can accurately estimate -- based upon well known soc statistics -- what the pfs for the treatment arm is.
If we get nothing we will be in the fog a while longer, because we need to know how many controls and how many treatment members were added each quarter (or even better) every month.
I am sticking with the trial ending early:
Gilead stopped early with just 93% pfs improvement.
"PIII trial stopped early after interim analysis by an independent data monitoring committee found highly statistically significant efficacy for the primary endpoint of progression-free survival in patients receiving idelalisib plus rituximab vs. rituximab alone."
We would equal 93% pfs improvement with progression free survival at 15.64 months, or put another way, we would only need an improvement of 7.54 months. My ham and egg determination concludes we beat that by a comfortable margin.
The recommendation could come back as early as 6 weeks. Around January 24, 2014. It will be interesting.
Yes. I think it also helped to know the reason there was not separation from placebo on "Trail Making Part A" was because the test is not as demanding. Anyway, your point is far more profound -- by a country mile.
You need to look at the purposes a phase 2 trial serve.
Because PBT2 improves executive function (met statistical significance at both 12 and 26 weeks), this will be the primary endpoint in the phase 3 trial.
Because this was proven to be dose dependent (statistically significant), the correct dosage (250 mg) will be used in the phase 3 trial.
Because the sub-study from phase 2 demonstrated PBT2 reduces brain atrophy, this will likely be used as the secondary endpoint.
Because there was a signal that PBT2 also improves functional ability, this will likely be used as a tertiary outcome.
Its an orphan classification so the powering in the third trial will be, to use your word, "easier." The FDA is required to work more closely with PRANA where its treatment for HD has orphan status.
February 18, 2014
February 18, 2014
Finally, as Huntington disease and other neurodegenerative disorders progress, there is a gradual loss of brain tissue or atrophy. In Reach2HD, brain imaging using magnetic resonance imaging (MRI) was performed in a small subset of patients (n=6) to map anatomical changes in brain structure. In the combined PBT2 groups (n=4) a reduction in atrophy of brain tissue in regions of the brain known to be affected by Huntington disease was observed compared to the placebo group.
Dr. Diana Rosas, Associate Professor of Neurology at Harvard Medical School and the study's co-Principal Investigator who conducted the imaging sub-study commented: "Despite the very small number of patients in the sub-study, the data are suggestive of a beneficial effect of PBT2 in regions of the brain that are known to be vulnerable to Huntington disease."
I thought Smith's Market Cap determination was interesting. It is closing in on the 300 million threshold much faster than one would think. Good news on Tuesday, and we will be on the safe side of that metric. (Note: The AF rule -- only 300 million Market Cap stocks prior to NDA submission have a chance to get approval from the FDA. I'm not an AF fan, but he shared an important truism..)
Agreed RT11, and as you already pointed out, other studies have confirmed NWBO results.
"Dr. Keith Black, who is now associated with IMUC, conducted a clinical trial at Cedars Sinai with essentially a copy of DCVax-L, and obtained largely the same clinical results as shown in NWBO's phase I /II trials. Those results were published." Larry Smith
It is also very important to note a few other factors:
PFS, the primary outcome measure in the current phase 3 trial:
PFS NWBO in Phase 1 was 24 months
IMUC was 17 months.
OS, the secondary endpoint measure for NWBO in its phase 3 trial:
In Phase 1 was 36 months
IMUC was slightly more than 30 months.
The trial design for NWBO is much better designed with better powering, a trial group over 2.5 times the size of IMUC's, and lower endpoint hurdles. All these factors give a much better opportunity to show statistical significance in all measurements.
NWBO Phase 1 was 20 people.
IMUC Phase 1 was only 16
There are just a number of reasons why although IMUC certainly did not have a test "failure", NWBO has a better chance to show complete statistical significance with far more robust findings.
These are your arguments??? Let's drill down into them a bit…shall we?
Junhaeng argument #1. A completely different drug, that people believed in, recently failed in a phase III trial and therefore all phase III drugs will fail.
Response #1: You should not invest in Biotech Junhaeung.
Junhaeng argument #2. The DCVAX-L phase 3 trial arm has the sickest people.
Response #2: You know better than this Junhaeng. Those with TRUE PROGRESSION after initial chemotherapy and radiation are excluded from the trial completely. Those with suspected Pseudo-progression, which according to the LATEST STUDIES are far fewer than originally thought by the oncology community, are enrolled separately. These, as you well know Junhaeng, are not the sickest patients by any stretch of the imagination. In fact, Pseudoprogression represents swelling that at first looks like tumor growth but is really the tumor inflaming because the chemo/radiation treatment is getting a therapeutic response. In earlier studies it was thought that pseudo-progression patients actually faired BETTER than patients showing no progression at all after chemo/radiation, but after careful review, the school of thought is that these patients respond on average the same as people with no progression at all after chemo/radiation treatment.
Junhaeng, you are either a genius at being foolish, or you are deceptive. In either case, by recklessly spreading misinformation around, you are hurting people sincerely looking to invest and help find a cure for cancer. It is one thing to give honest critique, it is quite another to scare people with disinformation and keep them from making appropriate risk tolerance based decisions. These people are trying to help cure cancer. Are you trying to keep cancer around Junhaeng.
"IMO... Starting at 1:35pm Tuesday, NWBO Executives will update us all on the ground-breaking technology that so many CANCER PATIENTS have been hoping for." -- godawgs-428
The first 66 events hit on the late side of NWBO's prediction. This is a very good sign. First they predicted end of third quarter then on July 26 they moved their prediction to end of 2013.
It took 13 quarters to hit 66. That is about 5 per quarter. We know they are accelerating, so lets bump it up to 6 per quarter. That puts the next interim analysis at a little more than 3 months.
Interim 2 event mark should occur on or before middle of March 2014.
1st interim recommendation happens around February 10, 2014.
Yes. Unless they have data lock issues (unlikely with very straightforward endpoints), I think they'll squeak it into 2014. IMO Of course early successful halt is possible in as little as 8 weeks. One thing we know is that the first interim 66 events hit on the late side of their July prediction. This is a very very good sign.
I was waiting for end of day, but I will stop right now because my offer clearly did not state closing or opening price. See you in 2 months! Enjoy my last posts.
I think the hidden value for small investors, if they invest within their means, is PBT2 applicability to common age related dementia and things like Post traumatic Brain injury (think NFL, Car Accidents, Soldiers, Boxing etc.) Like Doctor Tanzi stated, lightning does not strike twice, but in HD and AD it did on executive function and specific parts of the brain. Now we know PBT2 has preclinical applicability to common age related dementia, and yet again, it is preventing brain atrophy and improving executive function.
I know this does not fit the idea in this topic (aka: The closer you are to the treasure chest….); but there is another saying. Go with the big dog. In other words, once PRANA shows good results in the imagine trial, funding, promotion and many other factors will bring these untapped market potentials front and center into the public "imagination."
Yet another reason to expect better results this time around is that the they are using the highest efficacy dosing levels determined from the first phase. Forgot to mention that.