NorthWest Biotherapeutics Inc (NWBO)

[pgsd]

As we await the new FDA guidelines being implemented, these are some of the excellent points raised by NWBO and LL and put forward for consideration.

Comments from NWBO:-

"Allowing efficacy to be assessed using external controls will be far more ethical and also far more
feasible and affordable. Especially in diseases such as Glioblastoma, in which patient survival has
not improved by more than a few months in the last 30 years, and in which the course of disease is
strikingly consistent, it is really unethical to require a new cohort of patients to be assigned to
placebos in every trial.
Allowing efficacy to be assessed using external controls will also alleviate major bottlenecks in the
development of new medicines. Especially in areas of significant new drug development activity,
such as immune therapies for cancer, it is very difficult for sponsors to enroll and retain patients in trials with placebo control arms"

"In regard to sub-groups… when a trial fails to meet its endpoints with statistical significance in the
overall ITT population, but does show meaningful benefits in a definable sub-group, we strongly
urge that that drug be approved for that sub-group based on that trial, and that the sponsor not be
required to start over and conduct another whole trial in just that sub-group population. Such
approval should be allowed regardless of whether that sub-group was pre-specified or not"

"It is not fair to patients for a potentially helpful new medicine to be blocked from approval by the
rigid application of p value measures that even professional statisticians oppose. In addition – as
with the rejection of sub-groups – the rigid application of p values to refuse product approvals is
something that the healthcare system simply cannot afford. Each time a new medicine is rejected
on this basis, it adds enormous development costs. It also prevents new competition by the new
medicine. All of these factors are leading to the skyrocketing drug prices"

Comments from LL

"One problem with finding GBM cure, according to Liau, the fact that the disease is so heterogeneous - that it presents differently from patient to patient - means that the standard clinical trial approach has so far been less than helpful when it comes to identifying a cure"

"Liau thinks comparative analysis may be a good start, allowing physicians to treat patients individually, rather than by strict adherence to standard trial protocols"

"I must get a dozen or more emails or calls every week from random people about how they can get the dendritic cell vaccine, DCVax. And personally, I can'tone, I can't do that on a clinical trial. But even if it was FDA-approved, unless it's covered by insurance how do you pay for them? So, how do we fix that problem? All of these trials fail because the treatments don't work, but I think a larger part is we're not designing the trials right. But part of it is that it's difficult to provide these trials if you truly want to do what's best for your patient"

"For instance, I'll just take what happened with the DCVax. You really want to get clean data. We've never allowed for patients to get the vaccine once they failed, because they will. You enrolled in the trial. You had a recurrence, and now you'll have to try something else"

"So, a part of it is having the FDA think a little bit differently about what constitutes approval. On the converse, like the Optune device, that Novocure device, is FDA-approved. But I must say a lot of patients are like, "Well, I don't really like it." And I think on the physician side, we just don't understand how it works and there are a lot of problems with the clinical trial design"

https://www.regulations.gov/comment/FDA-2019-D-4964-0065