BETHESDA, Md., June 10, 2014 – Northwest Biotherapeutics (NASDAQ: NWBO) (NW Bio), a biotechnology company developing DCVax® personalized immune therapies for solid tumor cancers, announced today that it has initiated the Phase III trial of DCVax-L in Germany. The first site to open in Germany was a medical center in Dresden, which was initiated in late May. The Company has now scheduled the full-day site initiations for 3 more sites during June and 4 further sites in July.
To date, the trial has been enrolling in parallel in the US and Europe (in the UK), as previously announced. The first German site is now starting to screen patients for purposes of enrollment, and the additional German sites will begin doing so following their scheduled initiations (patients can obtain information about trial sites by contacting the Company at [email protected] ).
The process of initiating a clinical trial site (i.e., completing the steps required to enable a site to participate in, and to open enrollment for, a clinical trial) typically takes about 6 months for each site in the US. In Germany, there are several further steps involved beyond those in the US. The process can be conducted at multiple clinical trial sites (i.e., medical centers) in parallel, but the steps at each individual site must be done sequentially.
In the US, the steps required to initiate a site include the following.
- The first step is the "site qualification," in which both paperwork and onsite evaluations are done (of personnel, facilities, past clinical trial experience of both the institution and the personnel, etc.) to determine the capabilities of the medical center to serve as a site in the clinical trial. This step can take a month to arrange and complete.
- The second step is the review and approval of the clinical trial and all related documents (specific patient consent forms, data collection, etc.) by that medical center's "Institutional Review Board (IRB)." In many medical centers, the IRB only meets once per month. The clinical trial package must be submitted weeks in advance, and the IRB review, questions, further submissions, further IRB review and decision typically take 2-3 months.
- The third step is the negotiation of a business contract ("Clinical Trial Agreement") with the medical center's legal department and clinical trial budget with the medical center's budget department. The contract terms and budgets can vary substantially among medical centers within the same clinical trial. This process typically takes about 2 months.
- The fourth step is the "Site Initiation." This involves arranging and conducting a full-day, detailed, joint training of all of the personnel who will be involved in the trial: e.g., the neurosurgeons, neuro-oncologists, head of the hospital's pharmacy, pathologists, radiologists, nurses and others. The lead time for arranging this joint training with so many players on the same day is typically substantial. The training includes all aspects of the trial, including the patient eligibility criteria and procedures, treatment procedures, testing and monitoring procedures, data collection, etc.
Each of the above steps must be successfully completed before the next step at a site can be undertaken (because the sites will not proceed otherwise), and all of the steps must be successfully completed before a clinical trial can open for enrollment at that site. This lengthy process must be accomplished at each site individually for every site that participates in a clinical trial.
In Germany, for the DCVax-L clinical trial, significant additional steps must be completed in addition to the steps for US sites described above.
- Each clinical trial site must obtain a regulatory license for tumor tissue collection and use from the local regulatory authorities in the jurisdiction where the trial site (i.e., medical center) is located. The requirements of the local regulators for these licenses vary. The preparation of the appropriate application package for the local regulators, and the review, decision and issuance of the tumor collection licenses by those regulators, takes a couple of months.
- Similarly, each clinical trial site must obtain a regulatory license for the leukapheresis blood draw (to collect the immune cells) from the local regulatory authorities in the jurisdiction where the trial site is located. The local regulators with the authority over leukapheresis licenses can be different than the local regulators with authority over licenses for tumor tissue collection. The preparation of the appropriate application package for the local regulators, and the review, decision and issuance of the leukapheresis collection licenses by those regulators, takes a couple of months. Fortunately, unlike the other steps involved in clinical trial site initiation, the tumor collection license and leukapheresis license can proceed in parallel, so that these two licenses can potentially be completed simultaneously within a couple of months.
- At many clinical trial sites in Germany, multiple separate business contracts must be negotiated. Separate contracts must be negotiated with the radiology department and with the leukapheresis department, in addition to the Clinical Trial Agreement described above. The requirements and terms for these additional contracts vary from site to site, and must be negotiated individually.
As noted above, in Germany these steps are in addition to the steps described above which take about 6 months to enable sites to open for a trial in the US. Accordingly, the process is somewhat longer in Germany.
"We are excited to have the Phase III DCVax-L trial open for enrollment in Germany," commented Linda Powers, CEO of NW Bio. "It has taken a major team effort to accomplish the steps required for these sites. However, we are now ready to initiate a substantial set of clinical trial sites throughout Germany, and we have built a strong foundation for our clinical programs in Germany."
About Northwest Biotherapeutics
Northwest Biotherapeutics is a biotechnology company focused on developing immunotherapy products to treat cancers more effectively than current treatments, without toxicities of the kind associated with chemotherapies, and on a cost-effective basis, in both the United States and Europe. The Company has a broad platform technology for DCVax® dendritic cell-based vaccines. The Company's lead program is a 312-patient Phase III trial in newly diagnosed Glioblastoma multiforme (GBM). GBM is the most aggressive and lethal form of brain cancer, and is an "orphan disease." The Company is under way with a 60-patient Phase I/II trial with DCVax-Direct for all inoperable solid tumors cancers. The Company previously received clearance from the FDA for a 612-patient Phase III trial in prostate cancer. The Company conducted a Phase I/II trial with DCVax for metastatic ovarian cancer together with the University of Pennsylvania. In Germany, the Company recently received approval of a 5-year Hospital Exemption for treatment of glioma (brain cancer) patients outside the clinical trial.
Statements made in this news release that are not historical facts, including statements concerning future treatment of patients using DCVax and future clinical trials, are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "expect," "believe," "intend," "design," "plan," "continue," "may," "will," "anticipate," and similar expressions are intended to identify forward-looking statements. Actual results may differ materially from those projected in any forward-looking statement. Specifically, there are a number of important factors that could cause actual results to differ materially from those anticipated, such as risks related to the Company's ongoing ability to raise additional capital, risks related to the Company's ability to enroll patients in its clinical trials and complete the trials on a timely basis, uncertainties about the clinical trials process, uncertainties about the timely performance of third parties, risks related to whether the Company's products will demonstrate safety and efficacy, risks related to the Company's and Cognate's abilities to carry out the intended manufacturing expansions contemplated in the Cognate Agreements, risks related to the Company's ability to carry out the Hospital Exemption program and risks related to possible reimbursement and pricing. Additional information on these and other factors, including Risk Factors, which could affect the Company's results, is included in its Securities and Exchange Commission ("SEC") filings. Finally, there may be other factors not mentioned above or included in the Company's SEC filings that may cause actual results to differ materially from those projected in any forward-looking statement. You should not place undue reliance on any forward-looking statements. The Company assumes no obligation to update any forward-looking statements as a result of new information, future events or developments, except as required by securities laws.