This was Smith on Stocks's comment, on the Avisol Partners's SA article, posted on Sunday, May 22, 2022 at 7:39 am
Smith On Stocks
Today, 7:39 AM
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I am in agreement with your key points and believe that the trial was a spectacular success. Understanding how pseudoprogression renders progression free survival meaningless, that median overall survival is the gold standard endpoint for oncology trials and that FDA in some situations may allow the use of external controls are critical to understanding why the trial was such a success. You do a good job on this.
The stock decline on May 10, 2022 was meaningfully abetted by Adam Feuerstein’s article on Stat News entitled “It took years, but the failure of Northwest Bio’s brain cancer vaccine is now in the open.” His report was widely circulated to news outlets, some of whom reiterated Feuerstein’s demonstrably false claims that the trial had failed. Feuerstein appears to have been a catalyst in the stock decline.
The number of market makers for Northwest is usually about 6, but on May 10, there were 13 market makers; more market makers facilitates shorting. Hmmm. There were 77 million shares traded on May 10 and I believe that based on past experience that 80% could have been counterfeit shares (created through naked shorting).
In this comment, I present Feuerstein’s report in full and my critique of his demonstrably false assertion that the trial failed. I have not edited the Feuerstein report in any way. However, I do add editorial comments at certain points to interject actual facts into what I consider to be his work of fiction. I am stunned at how he grossly misrepresented the results of the trial as presented at the New York Academy of Sciences on May 10. His comments are frankly childlike and totally misrepresent the data that was presented.
NYAS Presentation on DCVax-L Phase 3 Trial Was Extremely Positive
The NYAS presentation can be viewed on You Tube at this link. virtualtrials.org/...
Some of the key data slides are as follows:
Slide 29: Kaplan Meier analysis shows that DCVax-L met median overall survival primary endpoint in newly diagnosed GBM with a strong p value of less than 0.002.
Slide 30 Survival tail in ndGBM showed 13.0% of patients alive at five years versus 5.7% in control group. This is every bit as impressive as survival tails for the checkpoint inhibitors in recurrent non-small cell lung cancer and recurrent melanoma, cancers which are roughly equivalent to glioblastoma in terms of survival.
Slide 39: Kaplan Meier analysis shows that DCVax-L met median overall survival primary endpoint in newly diagnosed GBM with a strong p value of less than 0.001.
Slide 40:The survival tail for DCVax-L in recurrent GBM showed that at 30 months 11.1% of GBM patients were alive versus 5.1% in the control arm.
It is important to understand that the actual endpoints of the trial were median overall survival. These are described on the government website ClinTrials.gov. Here is the link. clinicaltrials.gov/... The phase 3 trial was designed to evaluate the impact on survival time, as well as safety, in patients following treatment with DCVax(R)-L, an immunotherapy treatment for GBM. The control arm was based on 1,366 patients who received standard of care in several glioblastoma trials that ran concurrently with the DCVax-L phase 3 trial. FDA officials in the oncology division have recently signaled that the use of external controls may be acceptable in some cases. See this link. smithonstocks.com/...
According to ClinTrials.gov. the primary study endpoint is OS (overall survival) compared to external controls in newly diagnosed glioblastoma, and the first secondary endpoint is OS compared to external controls in recurrent glioblastoma. In judging how dishonest the Feuerstein article is, it is critical to understand that progression free survival is not part of the statistical analysis plan. It is not even a secondary endpoint. However, Feuerstein claims that the trial was a failure because it did not show statistical significance on progression free survival. This is just a blatantly false representation of results.
The Feuerstein Report Blatantly Misrepresents Actual Results as Presented at NYAS
Here is Feuerstein’s full article with my comments interspersed.
It took years, but the failure of Northwest Bio’s brain cancer vaccine is now in the open
By Adam Feuerstein May 10, 2022
After years of delays and excuses, Northwest Biotherapeutics finally disclosed on Tuesday the final results from a late-stage clinical trial of its personalized cancer vaccine administered to patients with brain tumors. The treatment’s data are as bad as expected — performing worse than a placebo.
Patients administered the Northwest Bio treatment, called DCVax, went a median 6.2 months without their brain tumors returning compared to a median of 7.6 months for patients offered a placebo.
(SmithOnStocks comment: Progression free survival was not the endpoint. The endpoint was median overall survival as previously described.)
Overall, patients treated with DCVax had a 10% higher risk of tumor progression compared to placebo — an outcome that is the antithesis of what’s required from any effective cancer treatment.
(SmithOnStocks comment; This is meaningless).
DCVax is a cancer vaccine, meaning it’s designed to stimulate the body’s own immune system to find and kill cancer cells. Some immunotherapies have been shown to prolong survival despite minimal effect on tumor shrinkage. That wasn’t the case with DCVax. The Northwest Bio study was also designed to measure and compare the overall survival of DCVax and placebo patients, but the company chose not to disclose those survival data on Tuesday — for reasons that are now clear.
(SmithOnStocks comment; The presentation clearly noted that the trial reached the primary endpoint of median overall survival in newly diagnosed glioblastoma multiforme with a stunning p value of <0.002. It also reached the secondary endpoint of median overall survival in recurrent glioblastoma multiforme with a p-value of <0.001. Feuerstein omits any mention of this and actually claims that survival data was not presented.)
The Phase 3 study enrolled 331 patients with newly diagnosed glioblastoma, an aggressive form of brain cancer. DCVax was administered to 232 patients; 99 patients received a placebo. The final data were presented at a cancer immunotherapy meeting sponsored by the New York Academy of Sciences.
Nineteen months have passed since Northwest Bio announced that the DCVax study had reached “data lock” — a standard step in the closure of a clinical trial that ordinarily leads quickly to data analysis and the announcement of the study outcome. “We are excited to be so close to the finish line now, after such a long road,” said Linda Powers, Northwest Bio’s CEO, in an Oct. 5, 2020, press release.
Instead of acknowledging the futility of its brain tumor treatment, Northwest Bio used the long interregnum to concoct a false, alternative reality in which the study was successful and DCVax extended the lives of patients.
To do this, the company discarded the overall survival data from the 99 patients randomized to treatment with a placebo. Those original, prespecified data were thrown out, and replaced on a post-hoc basis with survival data collected from 1,366 patients who participated in five entirely separate and previously completed clinical trials.
(SmithOnStocks comment: The 99 patients randomized to placebo were not thrown away. Those who progressed were categorized as having recurrent GBM. After progression, they were crossed over to DCVax-L and they formed the basis for an analysis of median overall survival in recurrent glioblastoma multiforme. The p value for this group was stunning at <0.001.)
When the 233 patients treated with DCVax were compared to the 1,366 patients taken from “external controls,” Northwest Bio said it found a 20% relative reduction in the risk of death. At the median, the DCVax patients lived for 19.3 months compared to 16.5 months for the make-believe group of control patients.
(SmithOnStocks comment: Feuerstein mocks the use of external controls. However, key employees in the oncology section of the FDA recently published an article in which they stated that in some cases, it is appropriate to use external controls as a control arm. See my article Northwest Biotherapeutics: FDA Statement Regarding Use of External Controls in Clinical Trials is a Huge Positive at this link.
smithonstocks.com/...
Northwest was very careful to present results for their external controls in accordance to suggestions made by this FDA officials.)
When you throw a dart against a wall first, and then paint a bullseye, it’s really easy to declare a win. It’s not, of course. It’s cheating. And that’s what Northwest Bio did with the analysis of its DCVax study.
(SmithOnStocks comment: Seventy clinical trial investigators involved in the trial attested to the accuracy of the results. Feuerstein with his strong political science background maintains they are all wrong. He is delusional.)
Northwest Bio shares plunged 70% on Tuesday once the DCVax presentation concluded. After a brief rise to around $2 per share in the run-up to Tuesday’s event, the stock is now trading again well below a buck.
(SmithOnStocks comment: The only negative news on May 10 was the article by Feuerstein which was fed to news outlets and Wall Street trading desks. Feuerstein is taking credit and bragging about how he was able to crush the stock price)
No one was fooled.
(SmithOnStocks comment: No one is fooled by Adam Feuerstein.)
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