Biotech Values

[walldiver]

INGN article in SeekingAlpha blog...looks like the scammers are getting the full reaming from the biotech press.

SeekingAlpha
Introgen: Setting The Record Straight On Its Biomarker Claims
Tuesday February 27, 3:05 am ET
http://biz.yahoo.com/seekingalpha/070227/28098_id.html?.v=1

Charles Atan submits: The FDA's biomarker initiative and its relationship to Introgen's (NasdaqGM: INGN) proposed BLA for Advexin for the treatment of head and neck cancer will effectively determine Introgen's fate in the short term as well as the fate of Introgen's shareholders. Unfortunately, there has been no educated discussion from the Street about the FDA's stance on biomarkers and their applicability to NDAs and BLAs. Instead, the sellside focuses on and trusts completely in Introgen management. This unwavering trust has been abused by Introgen for many years. So let's take a look at a close look at what the FDA says about biomarkers.
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On February 14, 2006 the FDA issued a press release titled "New Federal Health Initiative to Improve Cancer Therapy". Introgen seized the moment and began a concerted effort to exploit an initiative that has no relevance to its 6 year old phase 2 data or its phase 3 trials as far as an FDA regulatory decision. Introgen's efforts began in force in May 2006 in its first quarter earnings announcement and subsequent conference call. On August 9, 2006, Introgen issued a press release stating that "the company and the FDA have reached agreement to incorporate the use of Introgen's biomarkers in the analysis of ADVEXIN clinical data in support of FDA approval of ADVEXIN p53 cancer therapy." The company further stated "We now plan to use the biomarkers to analyze our phase 3 patient data. The FDA has previously told the company that its Phase 3 trial data may be used for interim efficacy analyses".

And on a conference call on December 28, 2006, Introgen announced that they and the "FDA have agreed on the statistical analysis plan for the ADVEXIN Phase 3 clinical trials to support product licensure for recurrent head and neck cancers. The analyses will incorporate p53 protein and other biomarkers." The only statement of all of the foregoing that is remotely accurate is that Introgen plans to use the biomarkers to analyze their data. For all the FDA cares they can use an abacus or a slide ruler to analyze the data.

What is the Biomarker Initiative?

The first questions investors need to ask themselves are (1) what is the biomarker initiative, (2) how does the FDA define a biomarker and (3) what does Introgen mean when they say that the FDA has allowed them to use biomarker data to analyze their trials in support of approval.

The answer to the first question is that the biomarker initiative described in the February 14, 2006 FDA press release actually relates to a collaboration between the FDA, the National Cancer Institute and Medicare to improve and develop procedures for utilizing biomarkers in the DESIGN and analysis of clinical trials. As far as the FDA itself, the topic of pharmacogenomic tests and biomarkers in the context of drug development was previously set forth in great detail in an FDA guidance document dated March 2005. FDA, like Introgen says, welcomes the use of biomarker analysis from all drug sponsors on a voluntary basis. They do not, however, utilize the data for purposes of determining whether a BLA or a drug is approvable except in circumstances that are entirely different than the circumstances surrounding Advexin's ancient phase 2 studies and as yet incomplete phase 3 trials.

The FDA defines these voluntary types of submission as VGDs, or Voluntary Genomic Data Submissions. There are strict limitations set forth in the guidance with regard to how VGDs can be and will be used in the context of an NDA or BLA. FDA guidance repeatedly sets forth these limitations:

Data from a VGDS submission concerning a product under an IND will not be used for regulatory decision making...

The FDA will not use genomic information submitted through the voluntary process for regulatory decision making on INDs, BLAs, or NDAs...

Any data evaluation will be conducted for scientific and informational purposes — not for regulatory decision making.

Importantly, the purpose of the guidance set forth explicitly the FDAs intentions with respect to how the data would be used in regulatory decision making: "that is, when the data will be considered sufficiently reliable to serve as the basis for regulatory decision making; when it will be considered only supportive to a decision; and when the data will not be used in regulatory decision." Introgen's statements to investors explicitly state that their biomarker data will be used in a regulatory decision with regard to Advexin and that the FDA has agreed to do so. You can be 100% certain that this is not true.

While everyone may know what the term regulatory decision means, I'll set forth the FDA's definition in case there is any confusion. The term regulatory decision making "applies to decisions that FDA may make in the evaluation of pharmacogenomic information used to establish the dosing, safety, or effectiveness of a drug or biological product." The guidance further states that observational and exploratory biomarkers are insufficient for making a regulatory decision. It is clear that Introgen has done nothing more than make observations through the extensive exploration of their ancient phase 2 data and therefore it will not be used in the context of approval of Advexin.

The answer to the second question is that a biomarker, as defined by the FDA, is "A characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention." The FDA further breaks down biomarkers into two categories. These categories animate the FDA's potential use and interpretation of the biomarker and include (1) Known valid biomarkers and (2) Probable valid biomarkers. The FDA defines a known valid biomarker as:

A biomarker that is measured in an analytical test system with well-established performance characteristics and for which there is widespread agreement in the medical or scientific community about the physiologic, toxicologic, pharmacologic, or clinical significance of the results.

Clearly, Introgen's biomarkers have none of these characteristics and are therefore not considered a known valid biomarker. The FDA defines a probable valid biomarker as:

A biomarker that is measured in an analytical test system with well-established performance characteristics and for which there is a scientific framework or body of evidence that appears to elucidate the physiologic, toxicologic, pharmacologic, or clinical significance of the test results.

Introgen's p53 biomarker test may be measured in an analytical test system with well-established performance characteristics. Even if it is, however, the FDA tosses biomarkers into the "probable valid" bucket when "the data elucidating its significance has been generated within a single company" and "when independent verification of the test results may not have occurred." Both of these characteristics describe Introgen's p53 biomarker data.

Introgen will argue that there biomarker data is robust. However, here are the facts. An abstract from the First AACR International Conference on Molecular Diagnostics in Cancer Therapeutic Development reported on an analysis of the Introgen phase 2 studies with respect to the biomarkers. That abstract reports on data from 16 patients (which has somehow increased since the report was issued in September 2006) with known clinical outcomes and useable tumor samples. These 16 patients represent 7% of the total phase 2 population. The abstract was authored by Laura Licato, associate director for Clinical Research at Introgen and other Introgen employees, including Robert Sobol, both of whom stand to gain financially from the acceptance of their biomarker data.

This is not reliable evidence of the biomarker's validity and there is zero chance that the FDA will approve Advexin based on this biomarker outside of a de novo pivotal program.

Disclosure: Author has no position in INGN