Cell Genesys (CEGE) announced Monday morning that an interim analysis of their VITAL-1 Phase III trial for prostate cancer immunotherapy candidate, GVAX, has been completed and the study was recommended to continue. While a relatively expected event, any idealistic hopes of achieving statistical significance during the interim peek has officially ended and the wait until final analysis (2nd half of '09) begins for CEGE investors.
To preserve ethical blinding for the interim analysis, the Independent Data Monitoring Committee (IDMC) did not inform CEGE management about the data they reviewed, and all they reported was that the trial can continue. While not the statistical significance that few may have hoped, it certainly is better than, heaven forbid, receiving tragic news to stop the trial. In the investment world, this result should be considered a tie, with longs still convinced in the long term efficacy of GVAX, and shorts feeling confident the drug just doesn't work. CEGE shares traded rather quietly following the release/conf. call, and shares ended the day relatively flat.
I remain somewhat skeptical about GVAX achieving statistical significance at the final analysis next year, not because the drug doesn't work, but instead due to the shifting paradigm represented by cancer immunotherapies and their different behavior patterns than docetaxal (Taxotere), a poorly tolerated chemotherapy and standard of care incumbent for prostate cancer. Combine this skepticism with an internally conflicted FDA proving resistant to change, and it becomes readily apparent the commercialization of GVAX via VITAL-1 faces unfavorable odds. These long odds, however, are reflected in CEGE's market capitalization ($170+mm) as the market is clearly pricing them to fail. It will take an eternal optimist to expect any meaningful catalysts between now and 2009 despite management's insistence about upcoming conferences, partnership possibilities, and data releases regarding other ongoing GVAX trials. The best possibility for short term upside would be a partnership, but the payout and terms of such a deal would be less fruitful than if negotiated after a statistically significant final analysis. On the flip side, a partnership would ensure continued drug development in the event the ongoing GVAX trials miss their primary endpoint of overall survival.
For those value investors looking for Buffett like investments, CEGE is not the right company for you, but anyone looking for a compelling risk/reward with the potential for blockbuster returns, CEGE can find it's place in even a conservative portfolio. Let's dig deeper as I attempt a long case for CEGE as a speculative biotech play.
Interim Analysis
Bears may point to the interim peek as yet more proof that GVAX doesn't work, but the interim analysis is truly a non-event. CEGE never disclosed the allocation of the VITAL-1 study alpha, but due to the slow onset of immunotherapy treatments, have followed the O'Brien&Fleming approach to alpha spending. This approach would minimalize the penalty at the final analysis, even though it comes at the expense of stricter efficacy requirements during the interim, therefore making interim success unlikely. Bottom line is that the only pragmatic expectation from the onset was to fully complete VITAL-1 to get GVAX past the FDA, and it's fair to expect that management has powered the alpha to maximize the likelihood of success at final analysis.
Given what we know, it appears unlikely that any cancer immunotherapy will achieve statistical significance during an interim analysis until the FDA accepts new efficacy markers and embraces modernized design of clinical trials. This is a 'work in progress', and investors/patients will rely on highly impressive final results and impeccable safety profiles to gain approval. Dendreon (DNDN) has learned the FDA is not as merciful as it is political, therefore leaving the dying prostate cancer patients without any humane treatment options and dismisses the common sense approach of leaving treatment decisions between well informed patients and their doctors.
VITAL-2 Phase III Clinical Trial
CEGE is currently conducting two GVAX Phase III clinical trials for prostate cancer. VITAL-1, which I discuss above, focuses on GVAX vs. Taxotere in asymptomatic AIPC. VITAL-2 focuses on GVAX + Taxotere vs. Taxotere alone in symptomatic AIPC. I believe the VITAL-2 study is the best designed of all the cancer immunotherapy trials and supports the growing sentiment in the medical community that an immunotherapy treatment followed by docetaxel will solicit the most efficacious results. I am more confident that VITAL-2 will achieve statistical significance during the final analysis (late 2010) as Phase II trials results demonstrated a dramatic increase in this treatment arm (median survival > 35 months) vs Taxotere alone (median survival less than 2 yrs).
For investors, VITAL-2 provides a layer of protection in CEGE market cap in the event VITAL-1 doesn't meet it's intended objectives. While it's safe to say that an unsuccessful VITAL-1 will dent CEGE's share price, it will not be to the extent that many other single-shot biotechs face when rejected by the FDA. With a strong GVAX pipeline relationship with Johns Hopkins (also Leukemia), and enough cash,technology, and assets to keep their manufacturing facility and operations going, the current valuation offers minimal downside compared to the explosive potential of this groundbreaking form of cancer treatment.
The interim analysis for VITAL-2 is scheduled for early 2009, and any positive results, albeit unlikely, would provide a huge catalyst as VITAL-1 winds to completion.
Dendreon
Dendreon's (DNDN) Provenge and GVAX are both prostate cancer immunotherapies, however, with different treatment approaches. When DNDN received a vote of confidence from the FDA advisory panel in March, shares skyrocketed from $5 to $25 practically overnight. At the same time, CEGE also saw it's price scream upwards from less than $3 to almost $7, demonstrating the impact FDA validation of a cancer immunotherapy has on the entire peer group. This dynamic means that any good news for cancer immunotherapy is good news for CEGE. Both DNDN and CEGE are pioneering new ways to deal with the growing problem of prostate cancer and despite their obvious head to head competition, their true competition is with a conflict of interest laden FDA. The controversy surrounding the Provenge decision is bringing important attention to the cancer immunotherapy space, and CEGE investors should be rooting for DNDN to gain FDA approval regardless of it's implications in the commercialization landscape.
With this being said, I believe that Provenge has the best shot of gaining FDA approval as a standalone treatment, and GVAX has the best shot of gaining FDA approval for a combination treatment with Taxotere. Having seen what a nod by the FDA would do for either company's valuation makes the risk/reward attractive, and as such, I recommend investors to take small positions in both companies as a bet on cancer immunotherapies with proven safety profiles and compelling efficacy data.
Recession
As the US economy slides into recession, CEGE investors are somewhat shielded due to the lack of direct economic dependencies on the overall business environment. Development stage biotechs with a stockpile of cash are rather immune to the macro level conditions of the markets. This is best seen by YTD action with major indices are down over 8% and CEGE up over 10%. While other aggressive growth industries like solar are taking a licking as market speculators jump ship, there is little downside to CEGE at this point without a catalyst in either direction.
Additionally, biotechs like CEGE are prone to heavy shorting, and a recession market provides far greater shorting opportunities than this already battered bunch. Binary events will drive CEGE, not market events, and this could work to investors benefit during this period of macroeconomic uncertainty.
Mercy
Taxotere, the only approved treatment option for AIPC, has a vicious side effect profile and is frequently refused by patients who do not want to endure the pain associated with chemotherapy. The safety profile of cancer immunotherapies has given dying PC patients hope of another option that will not come at the expense of quality of life. Anyone who listened to, or was present at, the Provenge FDA Advisory Committee in March witnessed a 17-0 vote of safety and despite some weaknesses in the efficacy data, a voted 13-4 in favor of it's effectiveness. This was a vote for the patients who have only one treatment option available to them, the brutal Taxotere. This was a vote for the field of immunotherapy, which has gained serious traction in the CBER division of the FDA, NIH, NCI, and the oncology community as a whole. The FDA's subsequent non-approval of Provenge was unthinkable for investors, many in the medical community, but no group could have been more devastated than the dying prostate cancer patients desperatly in need of another treatment option.
The FDA has clearly lost it's way, and the biotechs, their investors, and most importantly, the patients left with nothing but hope, are dragged down with them. The next two years will prove pivotal as CEGE and DNDN complete their ongoing trials and demonstrate to naysayers once and for all that immunotherapies are indeed effective enough to let well-informed patients and doctors make treatment decisions instead of leaving them in the hands of an FDA worthy of investigation. With a valuation of less than $200mm and enough cash to stand their ground, CEGE is well positioned in this exciting space to show significant upside if the hope of it's various stakeholders are finally realized.