Inaccuracies happen, but they're responsible for what they sign. In this case I doubt a mistake was made anywhere. Theirs are consistent statements repeated in various ways we're debating. As for the report on enrollment, they wrote the statement for August filing and repurposed it in November 2008. The only thing that changed is a written out number "six" which became an "eleven"; three months after August with 11 sites open they enrolled 5 more patients; those are facts. And they specifically told us in 2013 that enrollment was brief in "2008" (see March 7, 2013 PR at the bottom to which the body of the article is gone from their website, but can be found on the web: "The Company undertook a limited period of enrollment in 2008, and then kept the trial going with the patients already enrolled, but suspended new enrollment due to resource constraints during the worst of the economic downturn, through the end of 2010. "). They mentioned nothing about double-blinded enrollment in 2009, only others here suggest it. I'm sorry but there's no way for me to interpret all their various statements to which speak of: a) limited funds, need financing b) the open arm screened almost 50 patients (I don't know about you, but I'd take my chances being enrolled into control and if so, then just drop out if I had been assigned to control) c) that double-blinded enrollment stood at or near 11 by the November 19, 2008. Even if I were to ignore Dr. Gruber's quote on June 3, 2008 on Overlook and NYU enrollment of 20 patients, it's still impossible for me to see a substantial double-blinded enrollment increase in a month from November 19 to December 31, 2008. No way for it to go from 11 to 22 in a month. For all we know enrollment stopped before the year end, as it was brief in 2008. But I stand by my view that the 5 unaccounted patients from the pre-suspension period would be "open" enrolled patients, bringing the total to 22 "open" and 11 "double-blinded"= 33 patients. I do not know the mix of those 11 enrolled double-blinded patients and how many would be Rapids. My concentration has never been to figure out enrollment once the trial resumed in 2011. I'll leave that for others to speculate for themselves. I only worked on the numbers that were apparent to me, and those were that of the 33 patients.
SEC 10Q June 2008 (filed August 19) Statement: We are currently recruiting patients with newly diagnosed GBM in a 240 patient Phase II DCVax®-Brain clinical trial. Subject to our receipt of sufficient funding to carry out the study we plan to carry out the study at 40 to 50 clinical sites.
SEC 10Q June 2008 (filed August 19) Statement: We plan to rely on our current DCVax®- Brain Phase II clinical trial as a single study in support of regulatory approval. However, to date, only six patients have enrolled in the clinical trial, which is designed to include 240 patients. Given our current lack of funding, it is unclear how quickly we will be able to increase enrollment, if at all.
SEC 10Q June 2008 (filed August 19) Statement: As of August 4, 2008, 11 sites are active and a further 31 sites are at various stages of the start-up process.
SEC 10Q Sept 2008 (filed November 19, 2008):
We plan to rely on our current DCVax®-Brain Phase II clinical trial as a single study in support of regulatory approval. However, to date, only eleven patients have enrolled in the clinical trial, which is designed to include 240 patients. Given our current lack of funding, it is unclear how quickly we will be able to increase enrollment, if at all.
It was also very clear that the almost 50 patients screened were entirely from Phase II Open study. Compare the filing in 2007 to 2009
10K 2007 (April 8, 2008): In December 2006, we commenced recruiting patients with newly diagnosed GBM in a 141 patient Phase II DCVax®-Brain clinical trial. We planned to carry out the study at 12 to 15 clinical sites. The study was designed as a randomized study in which patients received either DCVax®-Brain in addition to standard of care or standard of care alone. To date, almost 50 patients have been screened at 4 clinical sites. However, patients have been reluctant to enroll in the study when faced with a 33% chance of being randomized into the control arm of the study under which they will receive standard of care alone. In order to address this issue we redesigned the study as a randomized, placebo controlled, double blinded study with a cross-over arm allowing control patients to be treated with DCVax®-Brain in the event that their cancer progresses. The study size has been increased from 141 to 240 patients and is designed to enable us to petition the FDA for accelerated approval if the study generates results similar to those achieved in earlier Phase I studies. In order to enable rapid enrollment, we are in the process of enrolling 45 to 50 additional clinical sites for this trial. As of April 9, 2008, seven sites are active and a further 31 sites are at various stages of the start-up process. We are engaged in discussions with the FDA concerning the study design and end points. Depending on trial results, we plan to seek product approval in both the U.S. and the European Union.
10K year end 2008:
In December 2006, we commenced recruiting patients with newly diagnosed GBM in a 141 patient Phase II DCVax®-Brain clinical trial. We planned to carry out the study at 12 to 15 clinical sites. The study was designed as a randomized study in which patients received either DCVax®-Brain in addition to standard of care or standard of care alone. To date, almost 50 patients have been screened at 4 clinical sites. However, patients have been reluctant to enroll in the study when faced with a 33% chance of being randomized into the control arm of the study under which they will receive standard of care alone. In order to address this issue we redesigned the study as a randomized, placebo controlled, double blinded study with a cross-over arm allowing control patients to be treated with DCVax®-Brain in the event that their cancer progresses. The study size has been increased from 141 to 240 patients and is designed to enable us to petition the FDA for accelerated approval if the study generates results similar to those achieved in earlier Phase I studies. In order to enable rapid enrollment, we are in the process of enrolling 45 to 50 additional clinical sites for this trial. As of January 1, 2009, thirteen sites are active and a further 31 sites are at various stages of the start-up process. We are engaged in discussions with the FDA concerning the study design and end points. Depending on trial results, we plan to seek product approval in both the U.S. and the European Union.
10K Filing (written another way, clearly the earlier patients are in the information arm; screening was not the problem):
In December 2006, we commenced recruiting patients with newly diagnosed GBM in a 141 patient Phase II DCVax® -Brain clinical trial. We planned to carry out the study at 12 to 15 clinical sites. The study was designed as a randomized study in which patients received either DCVax® -Brain in addition to standard of care or standard of care alone. The study was not blinded because there was no available approach for making a placebo that was indistinguishable from the DCVax®-L. Almost 50 patients were screened at 4 clinical sites. However, patients were reluctant to enroll in the study when faced with a 33% chance of being randomized into the control arm of the study under which they will receive standard of care alone. In addition, even patients who did enroll were reluctant to stay in the study if they were assigned to the control arm. Since the study was not blinded, patients were able to know which arm of the study they were assigned to. So, the Company stopped and undertook a development program to develop a placebo that is indistinguishable from DCVax
With the placebo developed the Company redesigned the study as a randomized, placebo controlled, double blinded study with a cross-over arm allowing control patients to be treated with DCVax® -Brain in the event that their cancer progresses. The study size has been increased from 141 to 240 patients and is designed to enable us to petition the FDA for accelerated approval if the study generates results similar to those achieved in the two prior clinical trials. We currently have 13 clinical sites that are qualified and ready to enroll patients. In order to enable rapid enrollment, we may add some additional clinical sites for this trial when resources permit. We are engaged in discussions with the FDA concerning the study design and end points. Depending on trial results, we plan to seek product approval in both the U.S. and the European Union.
BETHESDA, Md., March 7, 2013 /PRNewswire/ -- Northwest Biotherapeutics (NASDAQ: NWBO) (NW Bio), a biotechnology company developing DCVax® personalized immune therapies for solid tumor cancers, announced today that it expects to complete enrollment in its 312-patient Phase III clinical trial for Glioblastoma multiforme (GBM) brain cancer within a period that is faster or more efficient than relevant comparison trials with immune therapies for the same brain cancer. The Company anticipates completing enrollment of its Phase III trial by Q1 or early Q2 of next year, and expects to reach its first interim analysis for efficacy by approximately Q3 of this year.
Relevant comparisons include the following (according to information publicly reported on www.clinicaltrials.gov and in company announcements and filings):
Celldex Therapeutics (NASDAQ: CLDX) is conducting a Phase III trial with 440 patients, at 164 clinical trial sites worldwide, which began enrolling in November 2011, and appears likely to continue enrolling over at least a 4-year period through the end of 2015, with topline results expected at the end of 2016.
Immunocellular Therapeutics (NYSE MKT: IMUC) is conducting a Phase II trial with 124 patients, which were enrolled over the course of 7 calendar quarters from Q1 2011 through Q3 2012. (IMUC apparently screened 278 patients, but actually enrolled and treated less than half of them: only 124 patients were enrolled, in aggregate, and treated in either the treatment arm or the placebo arm of the trial.)
Agenus, Inc. (NASDAQ: AGEN) is conducting a Phase II trial with 55 patients, which began recruiting in Q2, 2009 and stopped recruiting in Q2, 2012.
NW Bio has primarily been enrolling its Phase III trial since Q2 of 2011. The Company undertook a limited period of enrollment in 2008, and then kept the trial going with the patients already enrolled, but suspended new enrollment due to resource constraints during the worst of the economic downturn, through the end of 2010. The Company began the process of reactivating clinical trial sites for new enrollment in Q1 2011, and resumed screening in Q2 of 2011.
NW Bio expects to complete enrollment in its phase III trial by Q1 or early Q2 of next year – an overall enrollment period of 14 or 15 calendar quarters, including both the 2008 period and the period since Q2 2011.
Notably, even if the completion of NW Bio's Phase III trial enrollment were to take substantially longer than the Company's projection of Q1 or early Q2 2014, the Company's enrollment would still compare favorably with these relevant comparison trials.
Statements on various NW Bio PR about the 33 Patients, and commencement of DCVax-L:
Bethesda, MD, January 24, 2011 – Northwest Biotherapeutics (OTC Bulletin Board: NWBO) announced today that the Company is resuming enrollment of additional new patients into its ongoing 240-patient, double blind, randomized, placebo controlled Phase II clinical trial of DCVax® for Glioblastoma multiforme (“GBM”) brain cancer.
To date, this trial has been conducted at 13 clinical sites across the U.S., with 33 patients already having been enrolled. These patients have continued to be treated with the DCVax® regimen and follow-up during the last two years. The only aspect of the trial that stopped for a period of time was the enrollment of additional new patients beyond the 33 patients who were already enrolled and receiving ongoing treatment. The Company is now resuming the process of accepting additional new patients to complete the trial.
Bethesda, Maryland, May 3, 2011 — Northwest Biotherapeutics (OTC.BB:NWBO) today announced that four medical centers across the country are actively recruiting and screening to enroll additional new patients in the Company’s ongoing 240-patient randomized, double blind, placebo controlled clinical trial of DCVax® immune therapy for Glioblastoma multiforme (GBM), the most lethal type of brain cancer.
The four recruiting centers are located in New York (University of Rochester), Ohio (University Hospitals of Cleveland), Michigan (Henry Ford Health System) and Minnesota (Virginia Piper Cancer Institute at Abbott Northwestern Hospital).
Another eight medical centers, spread over multiple other states across the country, have been making preparations for additional enrollment in the ongoing GBM trial. At least four of these eight additional sites are expected to begin or resume recruiting and screening for such enrollment during this calendar quarter.
To date, 33 patients have already been enrolled in this ongoing 240-patient GBM brain cancer trial and its information arm, and have been proceeding through the treatment regimen and follow-up.
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And as for their January and May 2011 statement on enrollment, it was on enrollment. One does not enroll into a "compassionate" information arm, one fails main trial enrollment and is moved into a "compassionate" information arm.
I honestly believe they didn't have the money to enroll as they were trying to raise it. And, while they weren't enrolling they were ramping up sites, with the hopes of being able to catch-up on enrollment once substantial money came in. [SEC 10K 2008 (filed April 2009): In order to enable rapid enrollment, we are in the process of enrolling 45 to 50 additional clinical sites for this trial. As of January 1, 2009, thirteen sites are active and a further 31 sites are at various stages of the start-up process. We are engaged in discussions with the FDA concerning the study design and end point.]Unfortunately that didn't happen for a couple of years. Maybe they were waiting to see how the open data trended, who knows, but they stopped enrolling in 2008. Only language they used in their 10k was "active", and notice how it was back dated to January 1, 2009, likely in an effort to avoid disclosure of the study enrollment stopping. I believe they were looking to avoid a Cognate stop trial bill, and that's why they kept the trial open for a few more months, and instead focused on the least costly approach of adding sites.
Cognate Agreement
On July 30, 2004, the Company entered into a service agreement with Cognate Therapeutics, Inc. (now known as Cognate BioServices, Inc., or Cognate), a contract manufacturing and services organization in which Toucan Capital has a majority interest. In addition, two of the principals of Toucan Capital are members of Cognate’s board of directors and, on May 17, 2007, the managing director of Toucan Capital was appointed to serve as a director of the Company and to serve as the non-executive Chairperson of the Company’s Board of Directors. Under the service agreement, the Company agreed to utilize Cognate’s services for an initial two-year period, related primarily to manufacturing DCVax® product candidates, regulatory advice, research and development preclinical activities and managing clinical trials. The agreement expired on July 30, 2006; however, the Company continued to utilize Cognate’s services under the same terms as set forth in the expired agreement. On May 17, 2007, the Company entered into a new service agreement with Cognate pursuant to which Cognate will provide certain consulting and, when needed, manufacturing services to the Company for its DCVax®-Brain Phase II clinical trial. Under the terms of the new contract, the Company paid a non-refundable contract initiation fee of $250,000 and committed to pay budgeted monthly service fees of $400,000, subject to quarterly true-ups, and monthly facility fees of $150,000. The Company may terminate this agreement with 180 days notice and payment of all reasonable wind-up costs and Cognate may terminate the contract in the event that the brain cancer clinical trial fails to complete enrollment by July 1, 2009. However, if such termination by the Company occurs at any time prior to the earlier of the submission of an FDA biological license application/new drug application on the Company’s brain cancer clinical trial or July 1, 2010 or, such termination by Cognate results from failure of the brain cancer clinical trial to complete patient enrollment by July 1, 2009, the Company is obligated to make an additional termination fee payment to Cognate equal to $2 million.
During the three months ended September 30, 2008 and 2007, the Company recognized approximately $3.1 million and $1.9 million, respectively, of research and development costs related to these service agreements. During the nine months ended September 30, 2008 and 2007, respectively, the Company recognized approximately $6.0 million and $4.1 million of research and development costs related to these service agreements. As of September 30, 2008 and December 31, 2007, the Company owed Cognate approximately $1,126,000 and $0, respectively.
