Presented at Society for Neuro-Oncology Conference
Data Continuing to Mature, Particularly Regarding Long Tail of Survival Curve
BETHESDA, Md., November 19, 2018 – Northwest Biotherapeutics (OTCQB: NWBO) — (“NW Bio”), a biotechnology company developing DCVax® personalized immune therapies for solid tumor cancers, announced today that updated blinded interim data from the Phase 3 trial of DCVax®-L for Glioblastoma brain cancer were presented by Dr. Linda Liau at the 23rd Annual Meeting of the Society for Neuro-Oncology. The updated data through October 2018 have continued to mature since the prior interim data collection in March 2017, and indicate encouraging patient survival.
The trial remains blinded, and all of the interim data are on a blinded basis (treatment arm and control arm combined). A total of 331 patients were enrolled in the trial (referred to as the “Intent to Treat” population or “ITT”). The last enrollments were in November 2015.
Patients are continuing to move through time points based on their length of time in the trial. All of the patients were past the 1-year time point at the time of the 2017 interim data collection, and most of the patients were past the 2-year time point. The further maturation of the data from March 2017 through October 2018 has provided an opportunity for more patients to reach later time points (3 years and beyond), and enabled a more developed picture of the “long tail” of the survival curve to emerge. The long tail is a key focus with immune therapies.
Top 100 Patients
The top 100 patients in the trial (patients with longest survival times) can be viewed as one measure of a long tail of survival. The Kaplan-Meier (KM) derived interim overall survival (OS) data on these patients is as follows:
|Median OS From Surgery||95% Confidence Interval|
|2017 data||40.4 months||35.5 – 46.5 months|
|2018 data||58.4 months||45.9 – 94.5 months|
The survival of the top 100 patients does not appear to be fully explained by known prognostic factors. For example, only 8 of the 100 patients had the favorable status on 3 key prognostic factors combined: age <50 years, methylated MGMT gene status and full surgical removal of the tumor. The demographics of the top 100 patients are somewhat more favorable than those of the whole 331-patient ITT population in the trial, but are not greatly more favorable. The top 100 patients include more patients with methylated MGMT, but also include a substantial percentage of unmethylated patients.
Overall ITT Population (All 331 Patients)
To date, 90% of all patients enrolled in the trial have received the DCVax-L treatment due to the crossover option that was built into the trial design. The KM-derived interim data on the overall survival (OS) of the whole ITT population at various time points is as follows:
|Median OSFrom Surgery||Survival at1 year||Survival at2 years||Survival at3 years|
|2017 data||23.1 months||89.3%||46.2%||25.4%|
|2018 data||23.1 months||89.3%||46.4%||28.2%|
The demographics of the ITT patients in the Phase 3 DCVax-L trial are comparable to the ITT patients in other late stage clinical trials for Glioblastoma, and the patients were enrolled at the same stage as the patients in the other trials (after the 6 weeks of standard of care radiation and chemotherapy).
A key factor affecting survival in patients who receive standard of care treatment for Glioblastoma is whether their MGMT gene is methylated (favorable) or unmethylated (unfavorable), affecting their response to Temodar as part of the standard of care. A breakdown of the KM-derived interim data on patient survival by MGMT status is as follows:
|Median OSFrom Surgery||Survival at1 year||Survival at2 years||Survival at3 years|
|2017 methylated||34.7 months||94.5%||66.7%||46.4%|
|2018 methylated||35.1 months||94.6%||66.6%||49.1%|
|2017 unmethylated||19.8 months||86.4%||32.1%||11.0%|
|2018 unmethylated||19.8 months||86.4%||32.6%||14.3%|
Ms. Powers, CEO of NWBio commented “We are excited to see how the data are maturing, and we are grateful to our Scientific Advisory Board for their strong advice not to unblind the trial too early. Had we unblinded earlier, the opportunity to see the fuller extent of patient survival would have been lost, and the potential would never have been known.”
“Until we reach data lock, the data will continue to mature. As we have cautioned before, the data may get either better or worse as they further mature. Also, the interim data are blinded aggregate data, and we do not know the breakdown between the treatment arm and the control arm of the trial.”
Ms. Powers continued: “We believe it is now appropriate for the Company to move forward with the several stages of work that are needed to reach completion of this trial program, despite the fact that there are good arguments for allowing the data to mature even further. The upcoming stages include finalizing the Statistical Analysis Plan, conducting the final data collection, data validation and data lock, and then unblinding and analyzing the data.
“Each of these are multi-month processes, and will involve tremendous work by both our team and teams of outside experts. In addition, virtually all aspects of the Company’s work involve pioneering. There is no well established pathway, and any projections or predictions are subject to material changes as we go along.”
About Northwest Biotherapeutics
Northwest Biotherapeutics is a biotechnology company focused on developing personalized immunotherapy products designed to treat cancers more effectively than current treatments, without toxicities of the kind associated with chemotherapies, and on a cost-effective basis, in both North America and Europe. The Company has a broad platform technology for DCVax® dendritic cell-based vaccines. The Company’s lead program is a 331-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 also pursuing a Phase I/II trial with DCVax-Direct for all types of inoperable solid tumor cancers. It has completed the 40-patient Phase I portion of the trial, and is preparing for the Phase II portion. The Company previously conducted a Phase I/II trial with DCVax-L for metastatic ovarian cancer together with the University of Pennsylvania.
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, although not all forward-looking statements contain these identifying words. We cannot guarantee that the clinical data will not change or mature adversely, or that we actually will achieve the plans, intentions or expectations disclosed in our forward-looking statements and you should not place undue reliance on our 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 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 ongoing ability to raise additional capital, and other risks included in the Company’s Securities and Exchange Commission (“SEC”) filings. Additional information on the foregoing risk factors and other factors, including Risk Factors, which could affect the Company’s results, is included in its 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. 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.