One of the more important issues discussed among physicians and investors alike when it comes to Dendreon (NASDAQ:DNDN) in general and Provenge in particular is the sequencing of this immunotherapeutic treatment with other agents. Critics of the corporation have longed voiced the opinion that Provenge would be overtaken by such drugs as Johnson & Johnson's (NYSE:JNJ) Zytiga (abiraterone) and Medivation's (NASDAQ:MDVN) Xtandi, pushing immunotherapy to the sidelines. But the fact is, sequencing of agents is more the norm than the exception in the field of oncology, and we would expect nothing less to be the case in the treatment of prostate cancer.
Even before Zytiga was approved by the FDA for pre-chemo use late in 2012 (based on JNJ's COU-AA-302 study, which did not achieve statistical significance for overall survival), the drug was being prescribed in Provenge's space. However, from the first, it was recognized that in many cases-especially where a man's disease load was low and not increasing rapidly-the drug would likely be sequenced with Provenge. To this end, the Journal of Clinical Oncology, concluded:
"The practical dilemma of the appropriate sequence of use of the two new noncytotoxic agents (sipuleucel-T and abiraterone) is being addressed by trials that are under development. For now, given the broader window of applicability of abiraterone and the longer time required to develop an immune response with sipuleucel-T, if both agents are to be used, it seems reasonable to administer sipuleucel-T first with Abiraterone after additional disease progression. Biomarkers to help define the optimal use of immunotherapy are needed."
Dendreon currently is running a sequencing trial involving Provenge and Zytiga, with the results to be reported later this year. According to the company, "[T]he purpose of this study is to evaluate the impact of concurrent versus sequential administration of abiraterone acetate plus prednisone on product parameters of sipuleucel-T, and to assess the safety and efficacy of sipuleucel-T with concurrent or sequential administration of abiraterone acetate plus prednisone in men with metastatic castrate resistant prostate cancer." The major concern here is that Zytiga requires co-administration with prednisone, which compromises the patient's immune system. Current thinking is that patients who are given Zytiga first must undergo a 60-day 'detox' period after completing their Zytiga regimen before Provenge can be administered. The current study should shed more light on this issue.
Meanwhile, others have begun to address the issue of sequencing agents in the prostate cancer space, including William K. Oh, MD, Chief of Hematology/Oncology, Tisch Cancer Institute, Mount Sinai School of Medicine, New York City. In a paper delivered at the 2012 Chemotherapy Foundation Symposium and discussed by Jason Broderick in OncLive, Dr. Oh examined the agents shown in the table below with the intent of 'determining a blueprint for sequencing.' He readily acknowledged that little data are available to drive the discussion but was able to distill four basic principles for sequencing the physicians could follow while the community awaited the results from ongoing trials. The basic principles can be found in Broderick's article, but the first is: Start with the most effective treatment with the least toxicity.
Recent Trials in Castration-Resistant Prostate Cancer (courtesy OncLive)
*Not statistically significant.
The results of Dr. Oh's work are summarized below. Importantly, he does not position Zytiga (abiraterone) together with Provenge (sipuleucel-T). The reason for this may be, again, that the results of JNJ's COU-AA-302 trial were not statistically significant for overall survival.
Current Treatment Landscape in Prostate Cancer (courtesy OncLive)
The results of Dr. Oh's and others' work suggest Dendreon's Provenge should be uploaded as early as possible for those who qualify for the treatment. Lending credence to this argument is the quartile study published by Dendreon last year, which showed that for a patient with a Baseline PSA less than or equal to 22.1, the median life extension benefit is a stunning 13.0 months. For a Baseline PSA between 22.1 and 60.1, the median life extension benefit dropped to a still respectable 7.1 months. Clearly, when it comes to using Provenge, the earlier, the better!
The Daily chart, courtesy StockChart.com, shows the stock closing Friday at $6.01, a nice improvement since I last wrote. The Relative Strength is in Overbought territory, and the MACD has turned positive. Resistance lies at $6.35. Perhaps the Street is sensing that company president and CEO John Johnson and his new management team have finally brought costs under control (especially with the sale of the recent New Jersey plant). As well, with the sales organization now coming up to full strength, the goal of reaching $100 million in quarterly sales-the cash flow breakeven point-should now be within reach. David King, manager of the Columbia Convertible Securities fund (MUTF:PACIX), was quoted in the latest issue of Barron's as being partial to a 2⅞% convertible from Dendreon , "…recently trading below 75 cents on the dollar and a 13% yield to maturity in 2016. … The company isn't far from cash-flow break-even and could be a takeover target," said King.
Regarding the Weekly data, the price is driving towards the first line of resistance, which lies just above $7. The Relative Strength and MACD are neutral.
Additional disclosure: I am long DNDN and the May 2013 $3 PUTs. I am not a registered investment advisor and do not provide specific investment advice. The information contained herein is for informational purposes only. Nothing in this article should be taken as a solicitation to purchase or sell securities. Before buying or selling any stock you should do your own research and reach your own conclusion. It is up to investors to make the correct decision after necessary research. Investing includes risks, including loss of principal. I am long DNDN and will not alter my position within 72 hours of the time of publication of this article. I am not a registered investment advisor and do not provide specific investment advice. The information contained herein is for informational purposes only. Nothing in this article should be taken as a solicitation to purchase or sell securities. Before buying or selling any stock you should do your own research and reach your own conclusion. It is up to investors to make the correct decision after necessary research. Investing includes risks, including loss of principal.