The CEO's Blog — Garo H. Armen

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March 30, 2007

Yesterday afternoon, an advisory panel of the US Food and Drug Administration (FDA) voted 13-4 in favor of approval of Dendreon’s prostate cancer vaccine, Provenge. This is a landmark event in the emerging field of cancer vaccines, demonstrating not only the clinical potential of this class of treatments but also signs of increasing regulatory flexibility that may help other promising cancer vaccines reach patients in a reasonable timeframe. As committee member Francesco Marincola, an immunologist with the National Institutes of Health, noted, “This opens up a whole new field of vaccine therapy that is very promising.”

Provenge and Antigenics’ cancer vaccine Oncophage are both patient-specific. Provenge is a cell-based therapy comprised of the patient’s own dendritic cells (specialized immune cells) that are processed to display a ‘shared’ antigen that is common to 95 percent of prostate cancers. Evaluation in late-stage prostate cancer patients shows a survival benefit of about 4.5 months.

Oncophage is a sterile protein preparation comprised of the unique ‘antigenic fingerprint’ purified from the patient’s own tumor cells. It is being evaluated to prevent disease recurrence in earlier-stage kidney cancer patients, which has the potential to have a longer-lasting effect on survival compared with the current paradigm of treatments primarily for later-stage cancer patients. Like most therapeutic cancer vaccines, both Provenge and Oncophage are regarded as generally safe and well tolerated.

Below I’ve outlined some key points about yesterday’s positive panel vote on Provenge and the implications for our clinical development plans for Oncophage.

FDA Advisory Committee Decision on Provenge and
Development Implications for Oncophage

Highlights from the FDA advisory committee meeting on Provenge

1. Dendreon’s Provenge cancer vaccine for prostate cancer is the first therapeutic cancer vaccine to undergo review of a licensing application by the US Food and Drug Administration (FDA) and to be reviewed by an FDA advisory committee.
2. Provenge is also the first autologous (derived from the patient's own tissue or tumor) vaccine for treatment of cancers to undergo review of a licensing application by the FDA and to be reviewed by an FDA advisory committee.
3. The general sentiment from the Cellular, Tissue and Gene Therapies Advisory Committee was that the decision on Provenge would represent an important advancement in the field of therapeutic cancer vaccines.
4. Although the analysis of the data did not fully establish efficacy, the committee nevertheless recognized that there was “substantial evidence” of efficacy in extending overall survival time in a post hoc analysis of a small patient population.
5. Testimony from patients and patient advocacy groups also appeared to positively influence the FDA panel in light of the highly limited and toxic current treatments. There was a very strong appeal for a product that could provide a better quality of life through non-cytotoxic means (much fewer and less severe side effects) even if it conferred only a slight extension on life.

What is the relevance of this development for Antigenics?

1. This is the first ever compelling indication of “the potential” as well as “the use” of therapeutic vaccines in the treatment of cancer patients in a commercial setting (pending final FDA decision). Until yesterday’s event there had been widespread skepticism about whether cancer vaccines could ever make it to the market. There are clear positive implications of this development for Oncophage and other therapeutic cancer vaccines: if Provenge is approved within the next two months, the field will no longer be hampered by the general inability of cancer vaccines to be approved.
2. Although the circumstances of Dendreon’s vaccine are different than those of Oncophage, we are very encouraged by the tone and approach by the FDA and the willingness of the advisory committee to recommend approval of the first of a new generation of therapeutic products representing a new treatment paradigm based on data that does not fit the standards of traditional regulatory guidelines.
3. This development also alleviates overall concerns and skepticism that autologous products cannot make it to the market based on regulatory complications. Once again, the implications of this development for Oncophage are positive to the extent that this issue has long been considered a general handicap.

What are the next steps for the potential approval of Oncophage by the FDA and other regulatory agencies around the world?

First, a summary of facts from our analysis conducted in November 2005 of our randomized renal cell carcinoma (kidney cancer) trial of 604 eligible patients:

1. There was a significant difference in recurrence-free survival (RFS) in a clinically and biologically relevant subset of earlier-stage patients (the target population subsequently labeled as “intermediate risk patients” by the Eastern Cooperative Oncology Group, or ECOG). RFS improvement in this setting means prevention of recurrence of cancer in patients whose primary kidney cancer has been removed with surgery.
2. This represented an early analysis, as the data were not fully mature based on the determination of an independent panel of radiologists. The review by this panel was a protocol-mandated procedure and the panel’s determination could only be made after the data cut-off date of November 2005.
3. At the time of this analysis, the RFS benefit did not translate to survival benefit in the same intermediate-risk patient subset.
4. Although there was a general trend indicating RFS benefit in all Oncophage-treated patients, there was also a trend against the Oncophage arm in the same overall population.
5. Oncophage appeared to be generally safe and well tolerated.

Subsequent to this, we shared our preliminary analysis of the data with the FDA. The agency acknowledged the potential beneficial trend in RFS in the earlier-stage population (intermediate-risk patients), which accounted for 60 percent of the eligible patients enrolled in the trial. However, the agency also expressed concern regarding the overall survival trend against Oncophage.

After these developments and based on the fact that the November 2005 analysis represented data that were less than mature, Antigenics made a decision to continue to follow patients for both RFS as well as overall survival until a formal cut-off date of March 31, 2007, which would clearly represent a more mature data set.

The purpose of the next analysis will be to determine the following:

• Is the earlier RFS advantage observed in the intermediate-risk population sustainable and will it be confirmed with analysis of more mature data?
• Is there a positive survival signal in the same patient population (which would be expected if the earlier RFS signal were real)?
• Was the overall survival disadvantage observed in the analysis of immature data an anomaly, and will it disappear or be reversed with the inclusion of more mature data?

If the outcome of this analysis (to be announced in early June 2007) is positive, we expect to request a pre–biologic license application (BLA) meeting with the FDA to determine the possibility of filing for approval. Concurrently, we will also explore the approval or conditional approval of Oncophage in renal cell carcinoma in other major geographies, including Russia, Europe, Canada and Japan.

This communication contains forward-looking statements that are subject to risks and uncertainties, including statements surrounding the presentation of data by Dendreon to the FDA, the impact this could have on the development of Oncophage, and the benefits to Antigenics. These risks and uncertainties include, among others, unfavorable data resulting from the analysis of the Oncophage Phase 3 Part 1 kidney cancer trial, the potential that the FDA will view Oncophage differently then Dendreon’s vaccine, the inability of Antigenics to retain key employees or raise sufficient finances to advance Oncophage, and the factors described in Antigenics’ Form 10-K as filed with the Securities and Exchange Commission on March 16, 2007. Antigenics cautions investors not to place considerable reliance on the forward-looking statements contained in this communication. These statements speak only as of the date of the communication, and Antigenics undertakes no obligation to update or revise the statements. All forward-looking statements are expressly qualified in their entirety by this cautionary statement. Antigenics’ business is subject to substantial risks and uncertainties, including those identified above. When evaluating Antigenics’ business and securities, investors should give careful consideration to these risks and uncertainties.

Comments

Posted by: Ryan (04/16/2007)
Comment: To all those who have and continue to work so hard, As shareholders, we cheer on a company because their success is our success. As a shareholder, I cheer on this company because lives depend on your success. Good luck.

Posted by: Luka (04/17/2007)
Comment: Congratulations on your work. My mom had glioblastoma; while it's too late for her I am sure other patients will appreciate any developments in this field. Thanks, Luka

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