Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
There are 2 parts to achieving an clinical endpoint. The first revolves around what you specifically state. The median values of each group. Because it is not the average or mean value taken, but rather the median, you are correct, once the > 50% of each groups's event occurs, that first part of the evaluation is complete.
So, no matter how long you keep the trial blinded, if there isn't a difference of ~ 2 months (in terms of DCVax-L's secondary endpoint OS) between the 2 mediums. The endpoint fails, end of story.
Part 2: However, if the 2 months difference does occur, well then that is when the longer the blinded data trial is kept going (meaning the higher the tail values will get), the stronger (or in this case, the lower the p-value) the statistical significance.
Not sure waiting longer time would greatly reduce the statistical significance. The statistical significance is reduced by how close the curves of each group follow one another. If they are identical, then the p value will be high. If they are identical until ~ 50%, and then one falls off and the other continues on a long tail, then the longer the tail the smaller the p-value.
So I don't think waiting longer will all of a sudden make the p value worse.
If P3 trial data is negative, NWBO wont have the funds to pay Les back, let alone anyone. Its do or die for them. Anything Les gets would be chump change compared to overall, AND, if he were to pay himself prior to other lien holders, he could leave himself wide open to numerous lawsuits.
Bad example.
How many days to report "good" news?
I agree! Great article!! Plus the author looks familiar!
Nice! I didn't even have to plug my own article! Now for the shorts and critics to sift through. Interested in how they will spin the information and analysis!
Thanks! If you look at the ITT SOC graph, <10% were PFS free at 16 months. The fact that we know there is 25% > or = to 15 months PFS free, and 10% that is at least > or = 20 months PFS free and that doesn't even include data from the other 2/3 of the patients, the PFS results for DCVax-L is outstanding!!
For 83 patients to be PFS by Jan/February, and using the ASCO enrollment curve which shows ~ 9 - 10 patients enrolled a month, and taking the last 83 patients, you would have a distribution of patients PFS free as far back as March 2015, meaning 14.5 - 23 months.
However, there is no way that 100% of the last enrolled patients were all part of that 83. Probably a good number of them were.
From SOC PFS curves, we know that 10-15% of GBM patients go PFS free > 15 months. So we know that since 83 patients or 25% are PFS free 15 months or more, there is no way these 83 patients are part of the normal SOC. Unless the SOC population somehow displays abnormally higher PFS results than what every other SOC trial has shown, we already know that there is a significant jump in PFS results.
Take another 80 patients having tumor progression within the 83 PFS free, which gives you 163 patients, and takes you back to June 2014 (coincidently 50% enrollment). That means the 83 would be PFS free between 14.5 - 30 months. And the other 80 we don't know. What we do know is that the other half, the 80 patients, that progressed, would have a PFS value between 1 and 30 months.
Maybe I will do a SA article. Blows my mind that investors haven't crunched these numbers and seen this. I still believe Big Pharma has it out for them.
Do you have the link to the ICT-107's PFS trial data. I would love to crunch those numbers. If I recall, mPFS from that trial was < 10 months; just over 9 I believe. ANd ICT-107 patients were mPFS ~11.3 months.
Flipper, I wasn't arguing, rather acknowledging your point. The link to the study I provided specifically shows probability of oncology trials in the last 10 or so years. And yes, it is lower at 33% - 40% success rate at Phase 3.
A whole paper on Trial Probabilities and Success
https://www.bio.org/sites/default/files/Clinical%20Development%20Success%20Rates%202006-2015%20-%20BIO,%20Biomedtracker,%20Amplion%202016.pdf
Historically, ~58% of Phase 3 trials have moved into a NDA/BLA with nearly 50% of all Phase 3 trials achieving FDA approval.
Now oncology is a bit different and the lowest probability of success, with 1/3 of all oncology P3 trials receiving FDA approval, and over 40% moving into a BLA/NDA. AND, if you look at rare disease phase 3 trial success rate numbers, you see a huge jump in approval success, with 65% - 72% if P3 trials succeeding. GBM is a rare disease, and DCVax-L has little side effects if any, so even if there seems to be increased success with a select portion of the patients, approval may be highly recommended.
No matter, the fact that there I believe the probability of DCVax-L's P3 trial succeeding, not taking any of the data that they have released to date into account, there is a 35% to greater than 50% chance that the P 3 trial will succeed, and the share price is 0.18 cents a share is an insanely good value investment. And by no means is it that they are likely to fail, but rather, wit the data that we know already (ATLEAST ~1/3 of the patients have are PFS > 15 months) jumps that probability well above 50%, IMHO!!!
Great info, my only 2 cents is in terms of equivalent share price, IMHO, is much larger than what you calculated. I don't disagree, I just think with positive P3 results, a share price between $15 - $25 is highly conservative. And here is why:
I agree with the US cases, however Europe has just as many, so even half of the markets of each, the US (7,000) and Europe (7,000), this would provide ~14,000 vaccines a year, at ~$150K ~$2B in revenue. Take Celgene for example, revenues of ~$6B in 2016, and a market cap of ~$100B. Using this as a comparator, the market cap with that $2B (1/3 of Celgene's) revenue potential alone would ~$35B, which provides a share price in the vicinity of $77 a share (using 450M shares).
HOWEVER, with positive P3 results, the immunotherapy door opens up wide, NWBO in a sense would become the first company to prove efficacy around immunotherapy, and with DCVax Direct already in the pipeline, as well as antigen targeting trial with Opdivo, a large positive light would surround NWBO's potential, allowing for a much larger jump in share price (at least initially).
I wouldn't doubt you could see a share price anywhere between $100 - $250 a share, at least as a high. There will allow be a correct, at least until revenues start rolling in.
Depends what lottery. Of course the Mega million is going to pay out way more, and reversely has an insanely improbable chance of success. Or someone can buy a lottery ticket from a state lottery with better chances than the Mega Millions, but still insanely improbable, and then they can guy a lottery ticket for a local 50-50, that costs ~ $1 - $2 and pays out $500 - $1,000, but still has a probability of 1 ticket in 1000 tickets.
However, I can buy $1 of shares for NWBO, and the payout could be $100 - $250 a share (depending on how long I hold those shares), and the payout would be $555 - $1389, which is 500 or more times the initial investment, AND, the probability is ~55%. (see probability reference here: https://biostrategics.wordpress.com/2011/06/27/clinical-trial-probability-of-success-just-how-probable-is-a-great-outcome/
So no, my analogy is COMPLETELY valid!
What I mean by lottery ticket is that, unless we are one of the one gathering the data, we don't truly know the outcome. I am extremely confident PFS will be met, OS on the other hand was a bit harder to prove without a doubt. No matter; when I say its a lottery ticket, the way I look at NWBO as an investment is exactly that. A lottery ticket. If you win, you win big, if you lose, you lose everything you put into it. HOWEVER, I feel that the difference between NWBO shares and a lottery ticket is that there is ~50% chance of positive results (probably much better but lets be conservative and use 50%), while a lottery ticket is actually 1 in 13,983,816. SO, yes buying NWBO shares at 0.20 a share, with a possible payout of ~$100 a share is like winning the lottery. However, the odds area much better than 1 in 13,983,816, with actually over 50% of P3 trials being successful, so you tell me, if you were told that you had a 50% chance of winning the lottery, would you buy a 20 cent lottery ticket? I sure would!!
My point is that the numbers unblinded to the statistician. And therefore are "unblinded". Data lock means all data is gathered including placebo or vaccine info and given to the statisticians
I wont argue with that!
Once the last 2 OS events occur, data lock will occur, and the statisticians will begin unblinding the data and crunching the numbers. I would think NWBO wouldn't release a PR when this happens, but rather, get the datalock, unblind the results, get everything evaluated and calculated, and then decide on how to release the information. Perhaps at the presentation in three weeks.
The longer it is without hearing anything, probably the better, as it means either the 2 events have taken longer to occur, OR, the data is good, because if it is negative results, then the SEC has a time limit as to when that information must be released, which is soon afterwards. With positive news, I believe they have more leeway to control the release of that information, such as at a Presentation.
I will say, even though a NWBO Long, I understand LP's wishes to stay autonomous, and not have to sign a deal with the devil (Big Pharma), however, if she had signed with Big Pharma, the there would be less payback (share price increase) with P3 success.
However, I believe LP's strategy was actually the best way to fund the P 3 trial, without significant share dilution in that she brought the share price back up over $1, and moved to the Nasdaq, and started getting institutional interest and investors. She was able to get the share price above $10 at one point, and had the share price stayed up, the additional funding/dilutions would have been minimal. I believe she should have probably raised more funds during 2015 when Woodford first bought in, but she probably thought the share price would continue to rise like KITE and JUNO.
That said, with the Phase V, and the easily seen, instant huge short volume sales, were used to drop the share price below $1. There is no doubt in my mind that there was a concerted effort to short the share price down in order to bankrupt or force NWBO to dilute their share volume substantially in order to finish the P3 trial.
If their P3 trial is positive, the ramifications are massive, as it literally puts NWBO in an extremely strong situation. They have Cognate's manufacturing ability to allow themselves to immediately ramp up productions, and gain revenue, AND, because of that, they can decide whom they want to sit down with. And there will be someone in the Big Pharma ranks that will make the jump, in order to get a leg up on immunotherapy. If P3 results are positive, that is. If not, NWBO is pretty much dead.
Its a lottery ticket right now, but with a hugely better chance of winning that an actual lottery.
Thanks for the update on no updates in July JDheart. I totally missed that.
I wouldn't attribute all 83 patients, as 10 - 20 of them could be either the long tail that doesn't see tumor progression 3 - 5 years (usually 10% of treated population), as well as patients enrolled Sept - Nov 2015. But I would say that the ~50 - 60 of those would be from the vaccinated population, and when you include others than would have had long PFS results, but weren't part of the 83, it paints a good picture in my mind.
It was the end of January 2017/beginning of Feb 2017 that NWBO stated that more than 248 events were reached.
Now, using normal math, we can determine, because of the halt in Aug 2015, and the enrollment, that the overwhelming majority of the 83 patients that were progression free were from enrollments prior to Aug 2015, < 30 were enrolled after Aug, up until the beginning of Nov. 2015. That means atleast ~60 patients were progression free ~15 - 17 months (depending on when the 248 occurred; Nov 2016 - Jan 2017).
We also know that it wasn't many in the lost to follow up, as 85 - 90% crossed over (85% had crossed over by Nov. 2016 from Liau presentation), meaning the majority of the 83 progression free survivors were initially vaccinated. Therefore we then know ~50 -60 patients of the 221 initially treated were progression free ATLEAST 13 - 17 months. That is nearly 30% of the 221. And that doesn't include the data from patients within the 221 that would have seen tumor progression but where treated earlier on in the trial, between 2012 and 2014.
Statistically it is almost impossible that DCVax-L failed on PFS. If anything, they show amazing PFS numbers. With the screen halt, and the enrollment schedule provided at ASCO, there is ~ 30% minimum patients showing PFS > 15 months, and that doesn't include any data from the other 2/3. So either those 83 patients were recently treated, or a good number of them have been PFS for a very long time like over 2 years. Since only 10% show long term PFS free results, it is more likely that there is going to be a significant shift in median PFS.
This probably means they are expecting news prior to August 25, 2017. Or at least I hope! :)
Yes, bioinvestor, I wasn't actually suggesting that Dr. Liau stated specifics on DCVax-L, my sarcasm may have been hidden a bit too well in my post. I was trying to explain that we do not know what Dr. Liau stated in her interview with the author. It could have been very different from the quotes provided. But we can definitely see where the author was going with their article, and I agree, the fact that Dr. Liau was a significant part of the article, and interview, translates that she is widely considered an expert, and highly respected in the field of GBM treatment.
"FDA approved expanded indication". This is what I read:
The U.S. Food and Drug Administration today approved an expanded indication for the Optune device to treat patients with newly-diagnosed glioblastoma multiforme (GBM)....
https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm465744.htm
It wasn't until mid 2016 they received full approval (and second generation device has been around since 2015).
https://www.novocure.com/novocure-receives-fda-approval-for-second-generation-optune-system/
The expanded indication was reviewed under the FDA's priority review program, which provides for an expedited review of certain devices that treat life-threatening conditions. So it looks like under the expanded indication, it still needed to show long survival results before gaining full approval.
Also, the more I read, I think the FDA was concerned that Optune would be used in lieu of SOC, which has not been proven to be effective. It must be used with SOC.
L. Liau stated "DCVax-L is truly the most effective treatment for GBM".
Milner is twists facts more than Bill O'Reilly himself. Only the reporter knows exactly what Linda Liau said, and from the article, and the fact that no other drug being currently tested, other than Optune was mentioned. And Optune being mentioned was barely touched on, and hardly explained.
The author's point was that there is no "one size fits all" cure on the horizon for GBM, but there is the potential for some vaccines/products that may have efficacy to specific patients. The author is trying to convey the harsh reality of the disease. To try and spin that Liau didn't plug DCVax-L because it isn't shown in the article is absurd. For all we know, Linda Liau said, "DCVax-L is truly the most effective treatment for GBM", but the author cut that from her quotes. If I were Reverse-Milner, I would just state that she DID say that.
Interesting about Optune. From what I am reading, Optune's P3 Trial at Interim analysis showed amazing results, and the news coming about back in late 2014 was that the trial was then it terminated due to early success at interim analysis. However, the trial wasn't terminated, (perhaps new enrollment was), but they continued the trial to look at long term results, which finally came out late 2016 (Nov) and it wasn't approved until recently in 2017. This tells me the FDA (and this is obviously FDA BT; Before Trump), wasn't taking interim analysis results, even positive ones, lightly. Novocure still had to continue the trial, to confirm results and long term specifically. Now, I am sure that many had Optune as being "weird science" and markedly, it is reflecting in its market cap of ~ $2B, less than KITE and JUNO and the cap is actually approved, however, that is probably due to the market potential in other cancer treating areas do not have as much potential as an effective immunotherapy treatment.
It does tell me that there is a reason NWBO has pushed the trial for as long as they can without taking data lock. If Optune had to continue their GBM trial for another 2 years after having their DMC recommend terminating the trial for early efficacy, then it makes a lot of sense why NWBO has pushed the trial another 6 - 7 months before data lock.
On a side note, what was the Optune Trial details? Was it double blinded? Meaning some patients had a placebo device they put on their head? I would think it was not blinded at all. Did they just take SOC data from patients outside their trial? Why would any patients sign up for a trial, and knowingly partake if they didn't get a device?
Liau didn't write the article so how can you say she didn't endorse DCVax-L. . The author doesn't mention one immunotherapy drug being tested. She only mentions optune but concentrates on immunotherapy drug development and the "tail" of survivors that do well on dendritic vaccines. If anything it highlights that Immunotherapy could be very effective for the specific people.
If P3 results are positive, and the share price takes off, I am sure that they would look to jump back to Nasdaq or NYSE. With positive results, it would be much easier for them to raise capital to increase manufacturing at Cognate and build a facility in Cambridge, UK. The last several years, with no income, and constant short attacking, they have had to offer substantial incentives (like additional warrants, and such), to raise cash to finish the P3 trial.
If they have a viable product that is approved, it will be easier to raise money within the bounds of Nasdaq or NYSE policies.
SHORTS ARE GETTING HAMMERED!!!
Look at the volume sales for the last couple days. Yes, share price has been stagnant, and yes shorts will argue it has fallen in the last couple days, but when you look at the daily share volumes being exchanged, you will see many large red volumes, meaning there were numerous large SELL volumes that shows shorts trying to push the share price down, however, buying volume has been constant, and as such, it keeps pushing the price back up. So for the last week, everytime the share price drops significantly from a short volume, it slowly creeps back up.
WHAT DOES THIS MEAN??? It means shorts are expending much more volume of shorts and they are unable to drop the share price much. Therefore, they are going to put themselves in a squeeze type situation if P3 data comes out. Even if they state the data has been locked, there will most likely be a nice jump in share price.
DCVax-L already starting to get in the news:
http://www.northjersey.com/story/news/health/2017/07/20/surviving-glioblastoma/495768001/
It is a story that has been updated.
No, yesterday's drop was pushed down by shorts, as you can see from the volume charts for the day. Large volumes pressured the price down below 23 cents, but constant buying pushed it back up over 27 cents and then shorting pushed it back to 26 cents. It looks like there is constant buying, and that the shorts are trying hard to push the price down, but doing little compared to the last year. This could mean they could end up with a whole lot of sold volume, but very little price drop. And if anything, JM will provide a huge amount of awareness regarding GBM, and probably the worse thing for the shorts. I hope JM finds something that works well, he is a great human being, and deserves a long life. Wish him all the best in this.
Listen, I agree, in terms of OS, the data known is difficult to prove mathematically that the OS known of the 100 patients alive is a bit more difficult to measure. Mainly that its currently ~ 20 - 21 months since Nov 2015. Though 70 of those patients are at least 24 - 25 months OS, which is nearly 1/3 of the entire population. However, since OS tails are thicker than PFS, it is a bit more difficult to state that the 100 could mathematically be a good portion of the tail, though SOC sees ~ 10% living 5 years or more, and 20% ~ 3 years, this could make up a good portion of the 100, (quick calc; 10% at 5 years; 9 patients, 15% at 3.5 years; 12 patients, 20% at 2.5 years; 18, and 37% at 20 months, 33; which gives 72 patients). Which means 30some patients over SOC. But that is probably too tight to be certain of. THE PFS NUMBERS, HOWEVER, are insanely better. Just say this out loud; 83 patients were PFS free 13 - 14 months or more (only ~7 of those 83 would have been 13 - 14 months, the rest would have been 15 months and greater). That is 25% of the entire trial population. Just over 10% of GBM patients in SOC get past 12 months. And no matter how you try and justify that the 83 patients are that 10% tail from SOC, it either means one of two things; the median PFS is going to be extremely high; 24 months or more, OR, the PFS tail is going to be extremely thick, meaning mPFS is 13 - 20 months with 30 - 40% of patients PFS free 20 months or more.
Another way to evaluate trial regarding PFS results:
Moreover, we know that since the 248 events did not occur until early this year, or late 2016, that there was 25% of the entire GBM population showing PFS results of ~13 - 14 months or greater, due to the fact with the trial halt back in Aug 2015, and last patient enrollment in Nov 2015. That also does not include any of the 248 patients that may have also shown to be PFS free more than 14 months. Lets look at it mathematically; 83 patients were PFS free Dec 2016. There was more than 300 patients enrolled by late Aug 2015, so there would have been less than 30 patients enrolled between Sept 2015 & Nov 2015. Assume 30.
Now, lets assume there is no efficacy, therefore, over 50% of those 30 would not have been PFS free for more than 6 or 7 months. Lets take 50% (to be overly conservative), that leaves 15 patients of the 30 were enrolled between Sept 2015 - Nov 2015 and with the lowest PFS free results, which would have been 13 - 15 months. Therefore, we know that 68 patients showed PFS results 16 months or greater. That's 20% of the entire trial population. And we know that at least 10 - 15% of the other 248 patients would have seen PFS free results just from SOC. So Take 248 - 15 (half the patients treated between Sept 2015 - Nov 2015), that gives you 233.
So lets forget that we know there is an unusual amount of PFS free patients > 16 months of the 83. And lets assume only 20% of the 233 are PFS free at 13 months (using Optune PFS graph), that's ~47 patients. Add those to the 83, and we get 130 patients or 40% of the entire treated population >13 months. If there is any improvement with PFS over SOC, then there only needs to be 35 more patients that are PFS free > than 13 months for that to be the median.
Now take 15% of SOC as > than 16 months. That would give 103 patients greater than 16 months PFS free; which is well over 30% of the entire trial population. That is a jump of 20% over SOC. AND, that's evaluating the entire population. From this alone, it strongly suggests there is efficacy in terms of PFS results, so NOW roll in that 1/3 of the patients are control group, which shouldn't see any PFS efficacy. You remove those patients that are PFS free at 13 - 16 months, which is ~17 patients, and that would mean that the majority of these 83 patients must be from the vaccinated group.
Another way to evaluate trial regarding PFS results:
Moreover, we know that since the 248 events did not occur until early this year, or late 2016, that there was 25% of the entire GBM population showing PFS results of ~13 - 14 months or greater, due to the fact with the trial halt back in Aug 2015, and last patient enrollment in Nov 2015. That also does not include any of the 248 patients that may have also shown to be PFS free more than 14 months. Lets look at it mathematically; 83 patients were PFS free Dec 2016. There was more than 300 patients enrolled by late Aug 2015, so there would have been less than 30 patients enrolled between Sept 2015 & Nov 2015. Assume 30.
Now, lets assume there is no efficacy, therefore, over 50% of those 30 would not have been PFS free for more than 6 or 7 months. Lets take 50% (to be overly conservative), that leaves 15 patients of the 30 were enrolled between Sept 2015 - Nov 2015 and with the lowest PFS free results, which would have been 13 - 15 months. Therefore, we know that 68 patients showed PFS results 16 months or greater. That's 20% of the entire trial population. And we know that at least 10 - 15% of the other 248 patients would have seen PFS free results just from SOC. So Take 248 - 15 (half the patients treated between Sept 2015 - Nov 2015), that gives you 233.
So lets forget that we know there is an unusual amount of PFS free patients > 16 months of the 83. And lets assume only 20% of the 233 are PFS free at 13 months (using Optune PFS graph), that's ~47 patients. Add those to the 83, and we get 130 patients or 40% of the entire treated population >13 months. If there is any improvement with PFS over SOC, then there only needs to be 35 more patients that are PFS free > than 13 months for that to be the median.
Now take 15% of SOC as > than 16 months. That would give 103 patients greater than 16 months PFS free; which is well over 30% of the entire trial population. That is a jump of 20% over SOC. AND, that's evaluating the entire population. From this alone, it strongly suggests there is efficacy in terms of PFS results, so NOW roll in that 1/3 of the patients are control group, which shouldn't see any PFS efficacy. You remove those patients that are PFS free at 13 - 16 months, which is ~17 patients, and that would mean that the majority of these 83 patients must be from the vaccinated group.
Interesting trading today - looks like shorts were trying to push the share price down, particularly at the beginning of the day with higher volumes, but as the day has gone on, constant demand or continually buying pressures keep erasing any short volume gains.
My analysis of today's trading is that there is a sustained, constant buying pressure, almost as if buyers are taking their time buying up any short pressures put on the stock price, and the shorts, well they continue to try and push the share price down, but end of feeding the sustaining buying demand. This is good for the stock, as it allows buying pressures to take a breath, and when there gets to be another glut of buying pressure, then the stock price may move up again.
That is what happened the last week on the Nasdaq, but the difference was the shorts would short a huge amount at the beginning of the day, to drop the price significantly, and then slowly move it back up by cover that and more throughout the trading day. That isn't the case the last several days.
Obviously something has happened. Either data lock, or positive news of the P3, and investors are buying in as slowly as they can without the price skyrocketing. Or shorts are trying to cover. Will have to see what the short volume has been last couple days.
That I don't know. It sounds like they flew to the US to get the vaccine, and so they didn't do it throw King's College or Fraunhofer, so am thinking they either have Cognate doing (which I doubt), or have someone in the US that gets the vaccine and then coordinates the shipment. Those containers look like they might be disposable as well. Meaning one time cryo-shipment.
Kat's Cure - Great to see she is doing well, and coming on 2 years this fall. Interesting to see the cryogenic containers with her next DCVax-L vaccination. I get inspired by such stories.
https://www.facebook.com/katscure/