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Summary

  • Many differing motivations lie behind our choice of words, but never more than when money is involved--even in scientific endeavors.
  • When comparing the methodology by which the Company discloses their ongoing Ph I results with other companies and their efforts, at worst NWBO seems mildly over-zealous.
  • Intratumoral DC vaccines have shown effectiveness of therapy long before DCVax-Direct came along--and not only in mice.

Dr. Aman Buzdar of MD Anderson may have overstepped his bounds recently by publicly stating his opinion regarding Northwest Biotherapeutics' (NASDAQ:NWBO) latest PRs on data from their ongoing Ph I/II DCVax-Direct trial, although not personally involved in the trial himself. In this unusual circumstance, the vice president of clinical research gave an interview to Adam Feuerstein of The Street, who many know has had a long history of releasing negative articles about NWBO.

Buzdar had not actually viewed clinical data, however, according to his own admission, but instead offered his opinion on the methods of press release based on the content in those PRs themselves.

The only issue of importance to an investor of NWBO is if Buzdar's comments somehow challenge the declaration of efficacy seen in early data from the ongoing DCVax-Direct trial. Do they?

Here is what he stated:

I have read the information that the company has put in the public domain. It is extremely unusual and inappropriate.

He does not clarify whether the information itself is unusual and inappropriate, or if simply releasing it into the public domain is, but it is assumed he meant the latter. In which case, that is incorrect. It is quite common for a company to release ongoing data of an open-label Ph I trial at any juncture they deem significant.

Here is one showing effectiveness of a whole tumor lysate loaded DC vaccine used to treat GBM (similar to DCVax-L) from a private Austrian company (not publicly traded). The trial was just a third of the way through, but that was enough for researchers to publicly announce data, being seen as positive. As they have no company stock, it was clearly not to "create tremendous hype," as Buzdar insinuated was NWBO's mission. There are other examples.

But who knows, perhaps it was NWBO's mission. The doctor seems to find this reprehensible, saying it is "very concerning to me as an academic oncologist."

Maybe so, but that did not prevent the doctor himself in his excitement to let the world know about his study, as yet inconclusive.

For the Company to release, verbatim, the data currently being seen in their DCVax-Direct trial, while at the same time cautioning investors just as Buzdar had in the link above that ongoing data is as yet immature and may change over time, shows no wrong doing or divisive handling. In fact, it is common and is what a biotech company ought to do to support their share price and potential funding that directly reflects the health of the same. Especially when the Company has had to face a barrage of bearish articles over the last year, negatively affecting their stock price. This has made financing difficult for the fledgling company, who clearly requires it to fund their trials.

However, the only comment that Buzdar made that calls the efficacy of the treatment into question was the following:

The weakness of this approach [in reporting results early] is that there have been many studies in which tumors are injected locally -- the injections could consist of anything -- and you see tumor regression because of necrosis caused by inflammation. But it is a tremendous leap to say that this is a real response, which is why what the company is saying is so inappropriate.

[brackets mine]

To be clear, inflammation alone cannot cause extensive tumor necrosis. Some, but not enough to show the results DCVax-Direct has: "In 3 of 9 patients, biopsies show no live tumor cells in the injected tumor." Mere inflammation simply cannot procure this.

But without a doubt, necrosis aside, inflammation cannot inhibit tumor growth and spread (metastases). And yet, for 9 out of 9 patients treated with DCVax-Direct after 4 doses (8 weeks, plus 8 weeks follow up--16 weeks into therapy), their far advanced, stage IV metastatic cancer has ceased progressing. They have achieved "stabilization of disease," according to official RECIST criteria. These are patients often given well under a year to live who are already at 4 months progression free survival--and counting. And a number of them are showing marked shrinkage of their injected tumors as well.

One patient's tumor reduced in size by 28%, and others likewise had substantial reductions--even at such an early stage of treatment. This after all chemos have ultimately been shown ineffective on them. Also, one patient's non-injected lung sarcoma shrank in size, showing systemic effect.

It should be noted that these are massive tumors. Some the size of a football. 28% reduction in one of these is the equivalent of complete elimination of 5-7 tumors of moderate size (3-4 cm) in terms of cellular necrosis and removal. That is a striking response.

Just how did that happen if the therapy is ineffective? Inflammation again? It appears rather that the dendritic cells are doing just what they're supposed to do--signal an immune response to attack the patient's tumor, and any metastasized cells they locate (much in the way a flu shot would cause one's immune system to seek out and attack that strain of flu virus).

There is also strong correlation between t-cell response (as has repeatedly been reported is occurring in the DCVax-Direct trial) and tumor cell death. Here is one study, and here is another.

But to look beyond the current DCVax-Direct trial for a moment, what's perhaps the most telling forerunner of intratumoral DC vaccinations and their potential effectiveness is found in a pilot study conducted by Triozzi.

In that study, Triozzi et al treated 7 patients with melanoma and 3 patients with breast carcinoma with intratumoral injection of activated dendritic cells. Partial and complete responses were observed in 4 patients with melanoma and in 2 patients with breast carcinoma (60%). Biopsies of regressing lesions showed t-cell infiltration and tumor cell necrosis (sound familiar?).

One patient with melanoma manifested a complete response of the injected tumor and eight other 0.5-1.0 cm non-injected satellite lesions within a 6-cm radius of the injected tumor, showing a systemic immune response. Was that the result of mere inflammation?

Overall, 6 of 10 patients showed at least 50% reduction in injected lesions - 1 of 10 had 25% reduction in their injected lesion.

Results would most probably have continued to trend positively in the Triozzi study, but they were cut short some 8 weeks into therapy. The reason being that in their cases resection was indeed still a possibility, and the technology used at that time (2000) had not yet advanced to enable researchers to inject intra-organ tumors with ultra sound guidance, as DCVax-Direct can.

For those in the DCVax-Direct trial, surgery is unfortunately no longer an option. This is their last hope. There is no chemotherapy or other treatment that has any effect on them any longer. And yet DCVax-Direct is already showing stunning results, even on such an advanced patient population.

It would be no real surprise if DCVax-Direct continues this positive trend. There is much veracity to the technology. Unlike novel synthetic drugs with no real precursor, DC vaccines utilizing whole tumor lysate have over 15 years of results in academia. The vast majority of which show effectiveness of therapy.

What would be strange indeed is if after this level of t-cell infiltration, tumor shrinkage, tumor necrosis (extensive cell death--some tumors seemingly completely filled with dead tumor cells), stabilization of disease, and marked improvement in quality of life, these patients should then experience no survival benefit. 9 of 9 patients that have received 4 doses are already at 4 months progression free survival (NYSE:PFS). And counting...

Whether or not one questions the motives of this company, one cannot argue with hard data. Saying merely "inflammation causes necrosis" is misleading--in an attempt to dissuade investors from being misled. What is interesting, however, is that Dr. Buzdar and Adam Feuerstein both admitted the results were positive when he quoted:

If you flip the coin and the trial results were negative, do you think the company would be disclosing this type of information? --Dr. Buzdar

In other words, the writer and the doctor quoted both admit results are positive, saying if they were negative the Company would simply say nothing. That is encouraging.

However, Dr. Buzdar may not offer the most unbiased source of opinion regarding ongoing data released from a small company competing with various large pharmaceutical outfits. Of note was a disclosure at the end of the following study:

Competing interests: Aman Buzdar is on the Speakers bureau and receives grant/research support from AstraZeneca and Genentech. He also receives grant/research support from Taiho, Lilly, Roche and Pfizer and is on the Speakers bureau for Amgen

Dr. Buzdar does not appear the most disinterested party in this regard, as the success of DCVax-Direct would be in opposition to the companies that finance his research.

To reiterate, Dr. Buzdar did not view DCVax-Direct clinical data and then base his opinion on it. He commented on comments made by a company who relayed information given to them from independent researchers who had in fact viewed ongoing data.

Obviously we must all decide for ourselves, and the data is in fact immature as of yet--but given the degree of effect already seen, which has grown stronger than that previously reported (increasing anti-tumor effects seen at 4 doses over 3 doses), and given the already proven effects of intratumorally injected DC vaccines (Triozzi et al), what I see in this apparently manipulated sell-off is a rather great buying opportunity.

Disclosure: The author is long NWBO. The author wrote this article themselves, and it expresses their own opinions. The author is not receiving compensation for it (other than from Seeking Alpha). The author has no business relationship with any company whose stock is mentioned in this article.

Source: The War Of Words: Balancing Perspectives On Northwest Bio's DCVax-Direct