Replies to post #157234 on NorthWest Biotherapeutics Inc (NWBO)

[Inspector Clouseau]

Thank you for all your hard work and updates.I have a little bit parked here and I'm not selling a single share.

[snoopycomic]

Thank you for the update. Much appreciated!

[Rootjim]

Interesting footnote flipper44. This is your last calendar update, until publication of blinded results , BLA information and/or top line data. You must believe were close to real news now.

[Doc logic]

flipper44,

Thanks for all the updates. The history of events helps highlight the ups and downs of trying to bring what we think is a game changing therapy for cancer into the market from a small biotech. Best wishes.

[xoma4578]

Thank you Flipper44.

[flipper44]

Latest flavor. The tail is the thing.

In immunotherapy, the big focus is the so-called long tail of the survival curve. That is the home run. And what it means to have the long tail, is that the survival steps down, and when people continue to live, the tail goes way out here to the right. If a treatment achieves a long tail, that's the home run. I mean, part of it is the slope of the graph, that's great too. But the big home run is the long tail. And you're seeing that being talked about with all of these therapies... with checkpoint inhibitors, everyone is super-excited because something like anywhere from 12 to 20% of the patients who respond in the first place are in a long tail and go for a couple of years. What people don't generally clarify is that even in the best case of cancers like melanoma where you're talking about a 25% response rate, you're talking about 25% of the 25%, talking about like 5% of the total participants in the trial.

If some treatment were to come along and have 20 to 25% of the total patients in the trial, that would be considered a very large tail, and the question is how big and how long. That's what we want to see, and that's what you as shareholders should want to see. We share your anxiousness like it's Christmas morning. But when we stop the trial and unblind, the data collection for the purposes of the trial stops. After that, we will never know the full extent of the long tail. The long tail is the key focus. -- Linda Powers February 7, 2018

So what is she referring to? "And you're seeing that being talked about with all of these therapies."
Here are a couple abstracts basically confirming what lp is stating. The first article is free.

Immuno-oncology combinations: raising the tail of the survival curve
Samuel J. Harris,1 Jessica Brown,1 Juanita Lopez,1 and Timothy A. Yap1,2

There have been exponential gains in immuno-oncology in recent times through the development of immune checkpoint inhibitors. Already approved by the U.S. Food and Drug Administration for advanced melanoma and non-small cell lung cancer, immune checkpoint inhibitors also appear to have significant antitumor activity in multiple other tumor types. An exciting component of immunotherapy is the durability of antitumor responses observed, with some patients achieving disease control for many years. Nevertheless, not all patients benefit, and efforts should thus now focus on improving the efficacy of immunotherapy through the use of combination approaches and predictive biomarkers of response and resistance. There are multiple potential rational combinations using an immunotherapy backbone, including existing treatments such as radiotherapy, chemotherapy or molecularly targeted agents, as well as other immunotherapeutics. The aim of such antitumor strategies will be to raise the tail on the survival curve by increasing the number of long term survivors, while managing any additive or synergistic toxicities that may arise with immunotherapy combinations. Rational trial designs based on a clear understanding of tumor biology and drug pharmacology remain paramount. This article reviews the biology underpinning immuno-oncology, discusses existing and novel immunotherapeutic combinations currently in development, the challenges of predictive biomarkers of response and resistance and the impact of immuno-oncology on early phase clinical trial design. -- June 2016, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944548/

Association of Immunotherapy With Durable Survival as Defined by Value Frameworks for Cancer Care

Article (PDF Available) in JAMA Oncology · December 2017
DOI: 10.1001/jamaoncol.2017.4445
Cite this publication

Omer Ben-Aharon
6.07Bar Ilan University

Racheli Magnezi
28.36Bar Ilan University

Moshe Leshno

Daniel Goldstein
34.3
Abstract
Importance Modern immuno-oncology agents have generated great excitement because of their potential to provide durable survival for some patients. However, there is concern regarding the cost of cancer care, and multiple frameworks have been developed to assess value. The American Society of Clinical Oncology (ASCO) framework awards bonus points if substantial durable survival is demonstrated. Objective To assess whether modern immuno-oncology agents reach defined efficacy thresholds in value frameworks. Design, Setting, and Participants In this analysis, all US Food and Drug Administration (FDA) approvals for immuno-oncology agents between March 2011 and August 2017 were reviewed. Data required for the ASCO framework were collected, specifically improvement in proportion of patients alive with the test regimen and survival rate with standard treatment. Main Outcomes and Measures Awarding of bonus points for durable survival based on the ASCO criteria. Results Twenty-three metastatic indications for 6 immuno-oncology agents (ipilimumab, pembrolizumab, nivolumab, atezolizumab, avelumab, and durvalumab) were approved by the FDA from March 2011 to August 2017. Ten (43%) of the approvals were based on survival end points, while 13 (57%) were based on response rates. Only 3 drug indications fulfilled the threshold defined for the survival rate of patients receiving standard care (minimum 20%). Nine indications achieved the required level of improvement in proportion to patients alive in the test regimen compared with the standard (above 50%). There was overlap between these 2 criteria for 3 drug indications, allowing them to gain the durable survival bonus points awarded by the ASCO framework. Conclusions and Relevance Durable survival and response rates of modern immuno-oncology agents are rarely recognized as significant by current oncology value frameworks. This may be due to insufficient demonstration of efficacy of such agents or inappropriately calibrated value frameworks. -- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944548/