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Northwest Biotherapeutics: DCVax's Path To Statistical Significance Remains A Mystery

Zhiyuan Sun profile picture
Zhiyuan Sun


  • At first glance, NWBO's blinded interim results appear to show robust efficacy in improving medial overall survival in Glioblastoma patients .
  • However, if this was the case, the trial would have been stopped early via the O'Brien-Fleming Boundary for success as with other standards of care for Glioblastoma.
  • Therefore, the drug likely encountered severe problems in achieving statistical significance as for the trial to continue under the banner of "capturing the long tail benefit of immunotherapy"
  • To make matters worse, the efficacy of DCVax has not been evaluated in studies for superiority against TTFields + Temozolomide.
  • The company is also extremely low on cash with no sight of when the 233th death required for trial conclusion will occur.

Image Source: Drug Target Review

After a follow-up review of Northwest Biotherapeutics' (OTCQB:NWBO) clinical data, I've uncovered more details about its flagship drug, DCVax, and its statistical validity. The findings are far from positive.

In two separate, blinded interim analysis conducted in 2017 and 2018, the overall cohort in DCVax-L Phase 3 clinical trial appears to show a 20-25% median overall survival benefit compared to the radiotherapy + Temozolomide + surgery treatment protocol for Glioblastoma. Despite nearly 90% of 331 patients have been administered with DCVax as per a cross-over protocol, however, it is impossible to determine whether patients living longer are due to the initial SOC treatment or DCVax because the vaccine never had an comparator arm in Phase 2 .

This isn't any new information NWBO shareholders aren't aware of already. 2 years later, however, the lack of any institutional investor interest in the company, combined with a crippling balancing sheet, should prompt an investigation to the validity of the clinical data.

Glioblastoma is one of the most invasive types of cancer with only 25% of patients surviving beyond year one and 5% patients surviving more than 5 years, for an average survival time of 12-18 months. Therefore, whenever new therapies are being investigated for the condition, interim analysis are frequently conducted and will be stopped early if the primary endpoint in such studies are met with robust clinical and statistical efficacy. This is done to ensure the expedited approval of the therapy as to save the lives of patients with this devastating type of brain tumor. One recent example of this phenomena is the approval of Tumor Treatment Fields.

The commonly used criterion for stopping a trial early is the O'Brien Fleming Boundary, which is a function of the total number of analysis conducted during a

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Zhiyuan Sun profile picture
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Analyst’s Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

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Comments (49)

Cora Schlesinger profile picture
Not on SA website. The last couple of links I posted never showed up. Maybe this time... Posting just in case it doesn't.

"The Flaskworks system is designed to fundamentally change the manufacturing process from artisan hand work to assembly line-like automation. As such, the Flaskworks system is designed to enable the scale-up to far greater production volumes. Technicians will oversee the automated systems (potentially multiple systems per technician) rather than making the products themselves."

Cora Schlesinger profile picture
NW Bio Announces Completion of Further Data Gathering For Phase III Trial

BETHESDA, Md., August 19, 2020 - Northwest Biotherapeutics (OTCQB: NWBO)(“NW Bio”), a biotechnology company developing DCVax® personalized immune therapies for solid tumor cancers, today announced that the remaining outstanding clinical trial data for the Company’s Phase 3 trial of DCVax®-L for Glioblastoma brain cancer as described in the Company’s last report on July 24, 2020 has now been completed by the specialty analytics firms. With this data now in hand, final quality control checking and confirmation are under way to enable Data Lock.

... When Data Lock is reached, the independent statisticians will be given access to the unblinded dataset. The Company will remain blinded while the statisticians make the computations, converting the mass of raw data from the trial into formal tables and listings, and survival and progression measures, to report the trial results.

...As previously reported, the statisticians’ work is estimated to take a couple of weeks. When their computations are completed, the Company will receive the results of those computations and thereby become unblinded. It is anticipated that the Company’s Scientific Advisory Board, the Steering Committee of the Trial and other key medical expert advisors will likewise receive the results, and thereby become unblinded as well.

...The Company currently continues to anticipate reporting topline trial data in September, and anticipates providing further updates as the process progresses.
Cora Schlesinger profile picture
This 8/19 (yesterday), 9:00 important PR never showed up on SA. They seem more inclined toward publishing negative news about this co. OTOH, AF refrained from making his usual vicious commentary, and in fact, made no commentary at all.

Cora Schlesinger profile picture
Never got there.
MachineLearning profile picture
MachineLearning profile picture
@Cora Schlesinger

I take that "thanks" back. Your link in is date July 24th. Show us the link that says data lock is "locked".
Cora Schlesinger profile picture
It's interesting that this announcement, released at 9:31 am, evaded detection by Clarke & SA, at least until the end of the trading day. If it were TSLA or one of the other companies they favor, it would have been reported at 9:32.

Bright spot profile picture
Wonder if the excitement of soon unblinded data and so forth is starting to wane? I'm excited, but I need to control my spending during these COVID times :) Guess I let what I have ride.
Bright spot profile picture
Now that the CD-19 isn't as bad as they claimed (Liberal Left) I've bought more of this stock.
Maiden35 profile picture
Great. The ASM is cancelled but they are still sending the “please donate” proxy to shareholders. All they need is a commercial showing half naked indigenous kids around a banana tree with flies crawling on their faces. This management is disgusting.
Bohsie Research profile picture
Where do you see that the ASM is cancelled???? Link please....
quackmaster profile picture
Nowhere can I find that ASM cancelled m
quackmaster profile picture
The shareholders meeting is TOMORROW.

David Innes confirmed to me via email.
Maiden35 profile picture
The idea that TLD will be discussed at the ASM is fantasy. That would be outright illegal. This is another religious stock with blind sheep investors. The Annual Shareholder Meeting is just another opportunity for the false prophet CEO to pass the offering plate. Sober up. Sell and get on with your life.
Bright spot profile picture
If you're so down on this stock, why are you flying around it like a fly around a turd? Maybe your getting ready to eat ****? Yeah, buy low, sell high :)
Maiden35 profile picture
With this risk off rout, lots of money that bought this stock around the .14 area over the last two years will be selling out. Selling brings more selling in this environment. No new buyers with the empty promise of “interesting” discussion and news “soon”. 15 years of total capital destruction. .004
Maiden35 profile picture
Who will lend NWBO anything is this environment? Nobody. Sell now.
Bright spot profile picture
This is actually the best time to get a loan for anything. Seriously, if CD19 takes you out, what? Me pay... LOL..... Something special is coming Maiden, just wait your turn.
quackmaster profile picture
Pharma doing quite well in this environment. Any of the big ones could easily buy out Northwest. Take the hate elsewhere.
Maiden35 profile picture
Forget about webcasts due to covid. Management will wait until the last minute and declare news “soon” after this has passed over. Every day is an opportunity to sell here before the stock hits .004
Maiden35 profile picture
Look for the “interesting” meeting to be canceled due to the conditions. Management now has the perfect excuse to go radio silent. More disappointment ahead for shareholders.
quackmaster profile picture
The shareholder meeting is tomorrow as planned. Stop spreading lies.
Cora Schlesinger profile picture
Not to worry, by his own admission, the author is "a statistician with a knack for analyzing clinical trials."
Bohsie Research profile picture
@Zhiyuan Sun I get the feeling from your comments (except this article to which you haven't replied to any comments) and articles, your short opinion on NWBO is influenced by your positive outlook on CVM. Almost like you feel a positive NWBO outlook is negative towards CVM. Understand that though these are two immunotherapy companies, they could both win with huge upside stock price potentials this April. NWBO has focused their initial vaccine on GBM, which is not where CVM has focused initially.
alphavestcapital profile picture
Zhiyuan: Because my friend is mesenchymal and methylated, Linda Liau's numbers says the median overall survival for his subset is 58.5 months.Where else can he get those odds other than by taking Dc Vax L?
NDHT profile picture
Sorry to hear about your friend.

I am not a statistician, but do know that one person's recovery does not mean DCVax L works for everyone, or others.

One example is our former President Jimmy Carter. It is said that his brain cancer went away due to the effects of PD 1 inhibitor. However, we know that Senator John McCain didn't make it.

Has your friend tried Novocure's Optune System?
Bright spot profile picture
Rumor is that John was using Optune. Might still be around on DCVAX L. We'll never know now. But the treatment was kept hush hush as far as I know.
alphavestcapital profile picture
DC VAX L , UPFRONT and PERSONAL: 3 years ago, a close friend found NWBO as an investment for our group.13.5 months ago my friend was operated on in Houston for GBM.After his operation, he traveled every 2-3 months to London to get DC Vax L injections under the Specials Program. Post his 1/23/19 first resection, his MRIs were clear until three weeks ago .And then they weren't, with three spots appearing .Today , his world class Houston brain surgeon exited the operating room telling my friend's wife," the spots were pseudo-progresssion. (www.pnas.org/...) I think Dc Vax L is keeing your husband's GBM at bay.". My friend has a 5 year supply of Dc Vax L shots frozen in London.He is 80 and wants to live at least 5 more years.He is mesenchymal and methylated. Everbody knows that with SOC GBM comes back about 6 months post initial resection. As to side effects, he had none from Dc Vax L.The chemo treatments made him feel awful. Why has my friend's GBM not come back ? He's out 13.5 months. Is it the Dc Vax L ? I felt so relieved with today's pseudo-progression news.It's just so strange that our American healthcare system is not making available to other GBM patients what my friend is experiencing. I have two other acquaintences who are not as fortunate . With their SOC, they are near death in under a year from diagnosis.

It’s time to put up or shut up. I think we all can agree on that.
sentimentstocks profile picture
You do know that when “20% of patients in immunotherapy trials” live longer if they’ve been diagnosed with glioblastoma (GBM), that is highly unusual, right? A patient diagnosed with GBM faces horrendous life expectancy numbers, with a little over a quarter of these patients living past two years!

Yet the blinded data from this trial described publicly to date has demonstrated that there ABSOLUTELY is a long tail, and therefore, it is completely justifiable, as you write, to “capture” it.

If 20% of ALL the patients who received DCVax-L in this trial live to 5 years, that would be phenomenal, and would represent a real game changer to both newly diagnosed and recurrent GBM patients. Unblinding the trial should be around the corner… one week, one month… with top line data soon to follow. If one chooses to take the time to pull apart and examine just the already presented blinded data, an astute shareholder would find they hold Topkapi’s Spoonmaker’s Diamond here.

While the length of time it’s taken to capture that tail has been pure torture to shareholders, having let it play out in real time will “explain” that the long tail can only be attributed to one thing - DCVax-L.
libouban profile picture
You wrote another negative article on NWBO on Feb. 5th this year, **less than a month ago!**

DCVax may be a platform technology against all cancer solid tumors. Have you even looked at the blinded data on MGMT methylated population? mOS at 3 years is at 49.1%. Let me repeat that. mOS at 3 years is 49.1%. For GBM.

Show me other studies with that ratio. Good luck.

I asked you in February about the scenario of DCVax L being proved positive and what this would do to the market cap. You did not answer. My own assessment in way over $1B .

You must know NWBio will have an ASM on April 18th and most folks who follow that stock expect the trial to be unblinded.

I am not impressed with your analysis, nor with your spin.
Here's a real life example of a person who received the DCVAX treatment for her brain tumor over 4 years ago and is still cancer free. Check out her facebook page. I'm sure there are many more stories like this where DCVAX has cured cancer.


"This week saw a huge milestone, the DVLA finally gave me my driving licence back after six years!!!

Four years ago I had been given 3 months to live, now i'm well enough to be allowed the simple pleasure of driving again and still tumour free thanks to DCVAX!"
jondoeuk profile picture
The plural of anecdote isn't data and as Dr. Novella once said: ''If you are basing your claims on anecdotal experience, then any treatment will seem to work for anything and everything.''
Bohsie Research profile picture
@jondoeuk That's true anecdote isn't data. Great point! You really nailed that one! One would want to evaluate the data itself, like the blinded results from DCVax-L and see that the effects are significantly better than SOC. Oh wait, you ignore that too. I guess you just argue whatever fits your argument or opinion!
sentimentstocks profile picture
lol... :)
Bohsie Research profile picture
@Zhiyuan Sun

If you want to compare DCVax-L Blinded mOS of 20.0 months to ITTFields (Optune), then you must compare it to the TTFields Blinded mOS result, which is less than 19 months.

Blinded Optune mOS = <19 months
Bldined DCVax-L mOS = 20 months

Blinded results include SOC & crossed over patients. How are you comparing DCVax-L OVERALL Population (which includes placebo and patients that crossed over and only started using the vaccine once the tumor progressed), against the Optune treated population. Tell me you understand how that isnt correct???
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