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All patients remaining in the trial will have their 5th dose by November 4, 2014 (at the latest). So the "fall" update on DCVax-Direct patient progress might follow that date.
However, there is a possibility the scientists simply want to finish analyzing every patient's tumor biopsy before reporting the entire post 4th dose results.
If the latter choice is made, I would not want to be on the outside looking in if and when the update hits.
(Hopefully MDA and NWBO took Ou's advice and worked out a formal interim update agreement.)
Note: It was reassuring to hear the 10 German hospitals receiving H.E. are in ongoing negotiations with NWBO regarding reimbursement.
Right. That is why there is an issue. LP makes it sound as though all 51 patients are true progressors and thought to be potential true progressors (aka: no pseudoprogressors). Slide 10 shows "pseudoprogressors" as part on the info arm, but slide 10 also has language suggesting "pseudoprogressors" and "potential true progressors" are different.
There is unnecessary confusion here that I thought might be settled during this presentation. It was not.
The most important new news from today's presentation.
1. Prior to receiving DCVax-therapy, Allen Butler "failed" (four months) chemotherapy.
2. Prior to receiving DCVax-therapy, Mr. Butler's pancreatic cancer already metastasized to his "liver" and "abdominal cavity."
3. The sarcoma patient referred to in an earlier NWBO PR is still doing "very well" and "very excited" as of approximately today.
These are new facts. They may seem like details, but let me assure you they should not be lost upon anyone. Ask any oncologist, any oncologist what Mr. Butler's odds of remission and/or cure were after failing (four months) chemotherapy for stage 4 pancreatic cancer.
I hope L. Smith stayed for the question and answer period.
I'd really like this question answered. In the informational arm, is NWBO defining "potential rapid progressors" and "pseudo-progressors" as the same thing. If so, I request that they only use "pseudoprogressors" (and stop using the word potential) If they are not using them the same way, they would do themselves a huge favor to clear this up, because I would be investing a great deal more if these patients were actually diagnosed true-progressors or thought to be true progressors as differentiated from pseudoprogressors.
Who heard the question and answer period following the presentation?
It looks like the informational arm will be explained further. Slide 10 looks extremely encouraging, but I'll wait for more detail.
Slide 10 is extremely encouraging.
How did you get the slides?
These are old. Today's slides will not be provided until the presentation begins.
Thanks John,
It looks like the U.S. will continue contributing to the 348 patient DCVax-L trial enrollment -- (along with the U.K and Germany.)
Neurosurgeon Arnold Etame, M.D., Ph.D., will lead the DXvax-L study at Moffitt, and he is looking for other newly diagnosed patients to take part. Moffit Cancer Center
Thanks for assimilating this so quickly Pyrr. I agree with your conclusion:
Like, HUH? -- Pyrr
What's up Dok!
Great comments and questions. I hope they are confirmed/answered today.
Long, I agree that the phase I approval for Keytruda bodes well for DCVax-Direct.
Remember the words of FDA Deputy Templeton:
"Dramatic enough" results can lead to approval for treatment even from a modest sized phase I study in a serious disease with only a single arm study held up against a historical control.
Keytruda's efficacy was established in 173 clinical trial participants with advanced melanoma whose disease progressed after prior treatment. All participants were treated with Keytruda, either at the recommended dose of 2 milligrams per kilogram (mg/kg) or at a higher dose of 10 mg/kg. In the half of the participants who received Keytruda at the recommended dose of 2 mg/kg, approximately 24 percent had their tumors shrink. This effect lasted at least 1.4 to 8.5 months and continued beyond this period in most patients. A similar percentage of patients had their tumor shrink at the 10 mg/kg dose.
Keytruda's safety was established in the trial population of 411 participants with advanced melanoma. The most common side effects of Keytruda were fatigue, cough, nausea, itchy skin (pruritus), rash, decreased appetite, constipation, joint pain (arthralgia) and diarrhea. Keytruda also has the potential for severe immune-mediated side effects. In the 411 participants with advanced melanoma, severe immune-mediated side effects involving healthy organs, including the lung, colon, hormone-producing glands and liver, occurred uncommonly. -- Link to fierce Biotech
Yes Ou, that is the question. Maybe they took your advice and arranged predetermined intervals with MDA to release this information. Smith also thinks the information should be released.
Clearly, the appearance of the M.D. Anderson doctors on a nationally aired television show can only be taken as their having strong support for the drug and Northwest. Also, the argument that talking about patient results before an unblinded trial is completed somehow exploits cancer patients can be quickly dismissed. Mr. Butler points out the importance of releasing information like this and clearly feels he was not exploited. He is extremely positive about giving patients like him, who have exhausted treatment options, the opportunity to find out about new therapies.
The bears have argued that the interim data that was published in the May 15th and June 11th press releases was unethical on Northwest’s part and was exploiting cancer patients. They also maintained wrongly that because Northwest had released the data, it had created a rift between M.D. Anderson and Northwest. A key point of this article is to show that this is also false. These major pillars of the bear case are now shown to be false.
I believe that there is enough evidence at this point to suggest that DCVax Direct has clinical and biological activity. I do not want anyone to come away with the conclusion that I am saying that the drug has been shown to be effective in some cancers. It is still early. However, there are good reasons to hope that DCVax Direct could be an important addition to the cancer treatment armamentarium. SmithonStocks
One other follow up. It appears the melanoma portion of the Keynote-001 trial had 411 patients (Perhaps fully enrolled). The rest of the trial is apparently composed of patients with metastatic carcinoma and non small- cell lung carcinoma -- all indications together were intended to comprise 1137 patients. This 411 patient trial was only used to determine safety.
The actual trial used by the FDA to determine efficacy was comprised of 173 patients.
Hodge posted (after Laurie received her fourth injection) that the protocol requires a biopsy in every patient just before each remaining injection. There are 6 injections in the phase I portion of this trial.
Agreed, that is why I stated we must wait for the details. I am interpreting the pipeline chart differently than you, but it could be read either way.
No doubt Ou. It was a shocker of epic proportions. However, I do have a theory about this.
There are a handful of companies that want to obtain approval for their (likely inferior) immunotherapies before DCVax-Direct. They might feel necessarily compelled to squeak in under the wire before DCVax is approved. In such case, these companies probably hope they can vy for potential adjuvant placement in DC-Direct therapy -- dependent upon the cancer type.
Technologies like anti-PD1, mitotic inhibitors, monoclonal antibodies and the like offered great hope for big pharma. I know you read Dr. Bosch's 2011 patent for NWBO. In it, he explains how and why big pharma failed to pursue dendritic therapy using completely autologous tumor lysate.
Anyway, If these very expensive technologies do not get under the wire before DCVax-Direct, they will face a likely far superior standard of care -- and therefore impossible enrollment accrual.
A few years ago, before I invested in NWBO, it occurred to me big pharma would be slow to react to a sea change. They would ultimately try to rely upon dramatically increasing mass marketing their inferior drugs, delaying the new competitive technology/company(s) through various means, getting what immunotherapy products they had to market -- no matter how inferior -- and generally start displaying a sense of panic. I assumed the FDA would only bend so far to accommodate this last gasp desperation by big pharma.
Now, I think am seeing/observing this in a slightly different light. We may see a couple more "shocking" immunotherapy early approvals before DCVax is approved. It will be very difficult for those companies to run confirmatory tests on their products if the world is flocking to DCVax-Direct. However, confirmatory trials as adjuvants to DCVax-Direct for certain indications could be their inroad.
Anyway, this is my current speculation -- for what that is worth.
Good point; still, due to the way immunotherapies work on various cancers, I believe tumor biopsy will replace tumor size as the primary determinant for response rates. I will not go deeply into that right now, but in some (many?) cases, immunotherapy can kill certain cancers and achieve a total response, even though the exoskeleton (if you will) of the tumor can remain for an indeterminate time.
Extremely Bullish! This may speed up Direct's timeline considerably -- but we must wait for Ms. Powers to confirm the details.
Consider Merck's immunotherapy product as a template (Keytruda's efficacy is likely inferior to Direct's). Keytruda is currently involved in multiple trials on multiple cancers, but it was approved and entered the market based upon its earliest released Melanoma phase 1 trials.
To determine Keytruda's efficacy, the FDA used Merck's smaller 173 patient trial. Overall Response Rate was 24%. (It was 34% in Keytruda's 411 patient trial.) I anticipate and fully expect to see far superior ORR in the Direct trial. (Remember, UCLA already conducted a phase 2 trial on direct and reported positively on its mode of inducing immune responses.)
Colon cancer metastases is likely the largest unmet market available. Any significant inroad toward treating this disease will not be ignored by the market. This is probably the best choice to move forward on first -- if one has to choose. It is probably the fastest way to ultimately get DCVax-Direct to all cancer patients.
As always, Smith is appropriately conservative; nonetheless, having digested Mr. Smith's articles and comments for approximately 2 years, IMHO the tenor of this article conveys unprecedented confidence.
Further Important Investment Implications of the National Geographic Segment
Having followed the development of cancer drugs for nearly 35 years, I am very cognizant of the danger and limitations of relying on the anecdotal stories of just two patients and incomplete, early results on about 20 others. However, the results are so striking that it does constitute an important signal that cannot be ignored even though we clearly need more data before we start drawing conclusions that DCVax Direct is an important new treatment option for some inoperable cancers.
The very encouraging experiences with the pancreatic cancer and sarcoma patients are further supported by data on other patients presented in a May 15th press release from Northwest Biotherapeutics which reported positive results from the DCVax Direct trial. This was then followed by a more important release on June 11th which discussed results of the first 20 patients treated in this 60 patient DCVax Direct trial; all patients in this study have some type of inoperable solid tumor. I would suggest that you read that press release for details but it reported that 9 out of 9 patients who have received 4 of the 6 planned injections of DCVax Direct were showing tumor cell death, tumor shrinkage, substantial immune cell accumulation in their tumors and/or stabilization (i.e., stopping the progression) of their advanced cancer. -- SmithOnStocks, September 8, 2014
LTT Said:
More anecdotal BS from SOS.
You don't invest in that kind of nonsense. Company has a enough going on for which there is inadequate disclosure/clarity. Focus on phase III trial....
By today, every patient currently in the trial has received at least four injections of DCVax-Direct and a concurrent biopsy. Of course, we know at least one patient already completed all 6 doses.
I'll probably be away for the rest of the week. A few non-investment related matters just arose. See you Monday:)
Agreed.
From what I can gather, the 1st dosed patient in the direct trial is demonstrating systemic results. He may appear television tomorrow. Then we have 9 of 9 responders after the fourth dose. There are other examples as well.
So, if adaptive licensing becomes a reality in the next 4-5 months in any country, I think it is reasonable to believe Direct could hit the market very rapidly. (Pyrr has written much more on this topic , and I intend to go back and review his prior thoughts.) Adaptive Licensing marketing approval is tentative but faster than AA.
The phase 1 results are far more important in the case of adaptive licensing. So LTT and AF's constant refrain that only phase III means something is obviously a deficient argument.
I think we are going to see a real watershed moment before June of next year for Direct.
This may sound like old hat musings, but I'm more convinced that we will truly be updated on Direct results at least twice before the final dose is given in February 2015.
It is likely that biopsies will replace tumor size as the closely watched endpoint for Direct-- for reasons you are already familiar with. Once people understand why this change is necessary, once they truly understand what this therapy is accomplishing, I think the ongoing results will actually hasten regulatory agencies to approve adaptive licensing far sooner than anticipated..
Yes. If we do not discount the entire chart, approval appears to average 2.5 years from the time the phase 1 trial initiates. That would place Direct on a very close approval course timeline with L. That is not an earth shattering proposal on this board, and it has been speculated upon a few times in the past.
My conclusion is the WIKI graph is deficient, because there are 2 FDA reviews required for AA initial approval followed by confirmation approval. It did not include the surrogate (AA) FDA review in its timeline.
1. Look instead at the pink line for expanded access on parallel tracks, then compare it to the red line for surrogate. Of course full availability on expanded use alone would take the longest, but limited use for expanded access often appears to start, on average, a short time before surrogate full availability.
2. The more striking thing about this graph to me is how early surrogate full availability occurs; yet look when FDA review begins!?! Full availability based upon a surrogate endpoint before FDA review starts and/or ends??? This does not occur in the other groups. I'd discount this as an averaging anomaly, but when one considers the accelerated approval process, there really is one official FDA review period....the one signified in the 3 other groups on the chart by blue (fda review) followed by red (full availability).
My thinking, with the limited time I have left this afternoon, is (in AA) the FDA review in blue is really preceded by an FDA review in say....orange. This is not signified on the chart. I need to go back and review surrogate accelerated approval again.
However, my guess is Pyrr could save me some time on this.
I know, it is wiki, but compare surrogate approval in this timeline for drug approval.
http://en.wikipedia.org/wiki/Clinical_trial#Length
Now check out the expanded access group timeline in the same chart.
I just want to reemphasize...or emphasize a point.
Some of the 55 patients in the informational arm very likely also included patients excluded from the main trial because they did not meet the following inclusion criteria.
Patients must have adequate bone marrow function (e.g., hemoglobin >10 g/dl, white blood count 3600-11,000mm3, absolute granulocyte count =1,500/mm3, absolute lymphocyte count =1,000/mm3, and platelet count =100K/mm3. Eligibility level of hemoglobin can be reached by transfusion.
Great insight Sentiment! Obviously they "reviewed or analyzed data," and for AF to say neither the CRO or the two hospitals conducting the study did this "at all" would be impossible. Moreover, the data must be continually reviewed for safety.
Thanks Evaluate,
It took me a couple times to get through this review, but it was well worth it.
This passage, also from page 5, seemed like it was describing many attributes DCVax already possesses.
The future of immune therapies in glioblastoma involves challenges related to enhancing antigen presentation capabilities, effectively breaking tumor-induced immune tolerance, improving a strong and long lasting anti-tumor T cell activation of tumor- specific cytolytic effector cells, and the standardization and upscale production of cell based therapy. Similarly, more clarification is required as to when and how immune therapy should be given with other modalities. The role of steroid and DC based immunotherapy use in this population of patients will require well-designed and appropriately powered clinical trials. -- Journal of Neurology and Neurosurgery Current Studies of Immunotherapy on Glioblastoma -- Neena Stephanie Agrawal.
NWBO is getting data from the pathology labs as well, so maybe we will get an update around September 9th -- once all patients have biopsies after their fourth injection.
The data released by the Company came from the medical files at the clinical trial sites and reviews of imaging and biopsies, and was provided by the sites and pathology labs, as well as a respected and independent clinical research organization (CRO) managing the trial. -- NWBO -- June 11, 2014.
For Due Diligence geeks,
Here are all the U.S. Northwest Biotherapeutic patent applications in one link. Use the search tools to sort by date.
https://www.google.com/search?tbo=p&tbm=pts&hl=en&q=inassignee:%22Northwest+Biotherapeutics,+Inc.%22&gws_rd=ssl#q=inassignee%3A%22Northwest+Biotherapeutics%2C+Inc.%22&hl=en&tbm=pts&tbs=sbdo:1
LP is not going to keep investors uninformed until the 2nd - 3rd quarter of 2015 just so you can trade on technicals. That is "redonkulous."
NWBO will not be intimidated by AF's (AKA: Ms. Manner's aka: Celldex groupie's) quest to squelch ongoing phase 1 observations and eventual phase 1 final results.
Your statement that only phase III trials matter would come as quite a shock to many drug companies that received approval on some of their products based upon phase II results. It is also laughable to investors that watched some of their stocks make their biggest moves after miraculous phase 1 results -- only to move upward at a slower rate thereafter.
I agree John. DCVax-prostate is far superior.
Spot on. I was wondering how this could be done in vivo with tumor lyses. I will review that process. If NWBO is not patent protected on non-solid cancers, then we are only 4 posts back. Regardless, while solid tumor cancers represent the majority, i'm thrilled the technology you spotted exists. I'll look into it!