Agreed

Affordy, foxy's english is spot on. His statistical points are also spot on. Just because you dont understand him does necessarily mean his writing is poor. The other plausible explanation is that your comprehension is poor...

Oversimplified explanation that completely ignores the role of cancer treatment and more specifically, at what stage in the natural history of cancer can a given intervention succeed.

Stage 4 patients are a heterogeneous group of patients that can be subclassified based on how far along they have progressed and how functional their bodies are.

Eventually they all end up with the same outcome but some will get there in a day and some in a month.

There is a point of no return. NO therapy can bring you back once you've crossed that point. Patients that are past that point should not be included in this trial. They are too sick to benefit from this or any antineoplastic treatment because main their problem is no longer cancer. Their problem is that their bodies are in the midst of a shutdown process. Their reserves are exhausted.

You need to be able understand which patients can be helped by dcvax. Not all stage 4 patients are the same.

Its NOT about massaging data or cherry picking patients in the negative way that uneducated investors/bloggers often use as an argument.

When you spew out medical terminology without a deeper understanding you mislead other investors that are wowed by your falsely portrayed expertise.

To sum it up in simpler terms, your post is full of...

icbs

Do you even know what those terms mean???

Please summarize the precise meaning of these changes.

It may be the simplest explanation but it is the least likely.

-We know this platform is incredibly safe, thats fact.
-We know they suspended screening but not further treatment of enrolled patients. If there was a safety issue they wouldnt continue treating anyone.

The most logical explanation is that the company submitted information from the trial which was NOT safety related. It happened when we hit 300 (exactly), which just happens to be the number of patients in the trial according to clinicaltrials.gov.

flip, how do you resolve your latest theory as to why they've halted at 300 and clinicalsites says 300 when they keep telling us 348. why be so ambiguous about it? either the trial is meant to enroll 300 or it is meant to enroll 348. i agree with you that it is curious that this number 300 has come up twice now.

Everyone is very hopeful that wednesday will bring amazing news. I want to offer a voice of caution.

The fact that the halt and potential for AA application occurred recently does not prove that this UK conference is when we will hear anything about this.

I believe we will hear something soon but am not convinced its this week.

Happy new year

Thats what this trial is about. Thats the whole point.

If you only invest in technologies that have been proven you will never invest in those that are unproven and therefore undervalued.

So let me understand the logic here:

Direct is better than L so L is doomed to fail.

(Iphone 6 is better so iphone 4 is doomed to fail)


Because the patent was issued 10 years ago L will fail.

(How many drugs' patents are issued 10 years before approval? Answer, all of them.)

Because the older version of dcvax used in L (efficacy not proven to date) doesnt use some secret ingredient (efficacy not proven to date) L is doomed to fail?

(I dont believe 'beam me up scottie' works, but if it did work it definitely would be the one in 'next generation' and definitely not the one in the original 'star trek'.


Your logic is ridiculously faulty. You are trying to draw objective conclusions based on subjective information.

Not really but the spirit is in the right direction.

Listen, its not that i disagree with your general analysis. And lets stop talking about safety already... Only people in lala land think that thats what this is about.

My only question is what the freeze and unfreeze mean. It sounds like we hit IA and went into a soft freeze. IM not clear about what happened next. Logic tells me that if it was unethical to give placebo and thus screening stopped, it should still be unethical to do so today.

But I admit that I have little true experience of these rules and regulations governing clinical trials.

I guess ihub doesnt like hebrew.

Ill transliterate it:

Lech le'azalzel

Lets examine the evidence:

Evidence that dcvax works? Provided at multiple time points.

Evidence that dcvax is unsafe? 100% safety record thus far.


Conclusion?

If i were a gambler, based on probability, i would choose halt for efficacy over safety without question.

Sorry, pyr, if you want to make money on puts or short sales, you should have picked a better strategy for scaring longs. Safety is NOT AN ISSUE.

As they say where i come from:
?? ??????

Flip, if they are suddenly restarting recruiting, it doesnt really support any scenario we've discussed. I dont see how this supports our AA theory...

We are speculating way too much in my humble opinion. We simply dont have enough info...

2 questions flip:

1) how did you get at june 15th as the initial halt? All we know of is august 3rd.

2) based on your assumptions and projections we will hear nothing until february 15th?

I dont believe our financials will last that long...

Its a good sign papa but dont jump the gun! Remember, the trial is blinded which means the nurses and doctors dont know who is getting placebo and who isnt. Their guess is marginally better than ours my friend...

If they told the public that there was a recommendation for a halt that would kill the trial. No new patients would agree to enroll because of the chance of receiving placebo. All patients in the trial currently would demand to know if they are on placebo.

No, pr'ing a recommendation without support from the FDA would be a disaster. Utter disaster.

August 3rd? Are we sure about that? RRR can you confirm this?

Thanks

Actually you do change your views, almost an hourly basis.

Now it sounds like you dont believe that they are pursuing AA. Yesterday you supported the idea. 2 days ago you thought they werent close tobthe end of the trial. 3 days ago you thought they were changing protocol to enroll children. 4 days ago tou thought they were adding japan.

Hard to keep track...

'Phase 3 data'

How is that data obtained is the question. Is it data from an IA or from a completed trial?

Im not sure about MHRA flip. For AA by the FDA it specifically mentions using interim analysis and proxy endpoints as a basis for approval. I havent seen that MHRA early access can be based on the same. 'Phase 3 results' reads to me as results at the end of the trial (reaching the primary endpoint).

Although I dont quite understand why one would need early access if the full phase 3 results are available...

Perhaps but they would never slow down the trial just to include children. They are a small subpopulation of GBM with less than 1/100,000 incidence. Its not something you can just suddenly do. The dosing is different for children etc. Way too complicated.

big veto.

children are not just small adults. FDA would never approve that and NWBO would never slow down a trial in a RARE disease in adults for an even RARER subpopulation.

yup. no need to dilute at todays prices if AA is around the corner. Maybe they stopped screening to allow them financially to make to the AA decision without going broke.

Flip check this out:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744277/

specifically:
"The FDA advised sponsors that future AA applications should preferentially be based on interim analyses of phase III (rather than phase II) trials, thus obviating the need for recruitment to additional confirmatory phase III trials.6–8 Also, FDA staff advised the ODAC and sponsors that single-arm, phase II studies are interpretable only for the purposes of AA applications in the setting of refractory disease. In contrast, interim analyses of phase III trials could support AA in a broad range of settings, and additional follow-up of these trials could provide evidence of clinical benefit."

"Response rates or times to progression were the primary surrogate end points in registration trials for 89% and 11% of the AA oncology NMEs, respectively. "

"However, since 2004, only 32% of oncology NMEs have received AA versus regular approval. This change coincided with the failure of gefitinib to show clinical benefit in its confirmatory phase III trial and with concern expressed by FDA officials at ODAC meetings in 2003 and 2005 that sponsors were not completing agreed-on phase III trials designed to verify improvements in clinical outcomes for AA oncology NMEs. To facilitate timely enrollment in these trials, FDA officials encouraged sponsors to base initial AA applications on surrogate clinical outcomes reported in interim analyses of phase III trials rather than on final analyses that identified improvements in surrogate clinical measures for patients enrolled on phase II trials.7"

Flip can you post where you got the details for this real world example from? What was the timeline? drug name? company name?

Thanks,
H

I doubt it. I think it has to do with the whole trial.

Right, after nearly a decade and hundreds of patients treated, not to mention a dmc recommendation to continue the trial in terms of safety, suddenly there is an serious safety issue?????

Nah. If there is one thing we know and have known, its that this platform is safe.

Nope, definitely not a safety issue.

Wrong again. (Wrong implies an honest mistake, my bad)

You dont ever crossover until the FDA says you can. That would be a point of no return. If the FDA asked them to continue they wouldnt be able to.

What will you say once its accepted for AA?

'What does AA really mean anyways guys? Accelerated using Einsteins theory of relativity may mean different things depending on how close you are to a black whole guys'

Btw, did anyone catch the fact that NWBO hacked mirriam webster and entered recruited as an adjective to enrolled??

Damn these scamming nwbo'ers are soooo good

Dont buy it. The GALENA example is a bad analogy. GALE demonstrated that in contradistinction to other HER-2 treatments, there is no associated cardio toxicity with their new phase III drug. So they received approval to not test for that (a safety issue that will save them money going forward in the trial).

Nowhere does it say that they stopped enrolling for this assessment. In fact it wouldnt make sense to do that.

You only stop enrolling if it is unsafe or unethical to continue.

Pretty straightforward in my mind. They are in the midst of interim analysis and submitted recommendations to the regulators for further guidance.

Why not treat new patients in the meantime?

If it were unethical to give a failing treatment they would also stop treating existing enrollees.

Maybe its unethical to give new enrollees the placebo...

How about this idea:

The PR states over 300 recruited. What if these 300 are the sum total of new patients waiting to be screened and some of them enrolled? In fact, why would you ever refer to an enrolled patient as recruited? Using this reasoning, all we know is that they have 300 patients that are ready for screening. If you assume they are on tract to end enrollment this year than those 300 should suffice.

Whats confusing is that they put these 2 numbers, over 300 recruited and anticipated 348 enrolled, next to each other. They arent necessarily referring to the same group of patients.

This is somewhat of a ridiculous post. The idea that at the last minute the company would try to change their protocol is ludicrous. This makes no sense whatsoever. Japan is also way out there. So you think linda woke up at 347 patients recruited and said 'oh that sushi last night was wonderful. Hey! Lets recruit one japenese person also! That way we will have access to a the huge japanese gbm population also!'.

I dont know what the real story is but these 2 ideas are NOT it.

Whoever trades this now should have their head checked out (happy to read youre mri brain for you ;))

Lolllll

Ive been invested in this stock for almost 3 years and as time goes by I am more confident about the direction the company and technology is going in. I'm not some expert on clinical trials, or immunology or even investing. But I am a logical person and I am a radiologist for whatever thats worth. What I've learned throughout this process is what people like Warren Buffet and Woodford continue to preach. Invest longterm in something you believe will succeed. Ignore the market. Most of the market is filled with sheep, being manipulated by a few wolves. Im not going to lie, my heart did skip a beat today. But the irony is it didn't bother me too much. I was actually too busy interpreting MRIs of people with prostate, kidney and liver cancer among other problems.

I have no sympathy for those shareholders that sold today. I know this will succeed and hopefully the patients I was diagnosing today will benefit.

You can't teach an impulsive sheep new tricks?

Im not evasive. I would just rather not give you more information that wont help you at all. But since you want the professional jargon Ill give it to you.

Necrosis looks like an area of decreased attenuation within a mass on CT scan and looks like an area of T2 and T1 prolongation on MRI. There is increased facilitated diffusion on diffusion weighted sequences. The post contrast images, in both modalities, show nonenhancement.

There, did this information help you?

Lol

L is in its final stretch. Im not holding my breath for Direct.

Dont know about CI and Direct. Maybe, maybe not. Who knows.

Intellectual masturbation at this point.

You do need to stop being lazy!

They presented actually images of the tumors in direct.

Necrosis is seen on cross sextional imaging, period.

Rkmatters and I are only debating the 25 indeterminates. The other patients were classified correctly per accepted criteria. They have markedly improved OS. L works even on rapid progressors. That is clear.

Again, this may be true in theory but practically speaking it does not discredit the efficacy of direct. Unless you are suggesting that chemotherapy induced necrosis is also useless.

Bottom line is if I see treatment induced dead tumor on a scan (avoiding the n word here) in a patient who no longer responds to any other chemotherapy that is an achievement. It may not be a cure but if it prolongs life by a few months with no side effects? Amazing.

This necrosis is an achievement in this patient population period!

Cant say. Only way to know would be to not give them a confounding treatment and follow them. The ones who die quickly are rapid. The ones who live long are pseudo. Thats the problem with this distinction, its only certain in retrospect. And once you give a new treatment that has an indeterminate effect you cant really know for sure. Without dcvax these 25 would eventually 'declare' themselves as rapid or pseudo. But with dcvax we cant know anymore.

If the 25 didnt meet criteria for true progressors or pseudoprogressors than why were they excluded from the trial...

Therefore the indeterminates cannot be considered run of the mill GBM. Otherwise they wouldnt have been excluded to begin with!