Last week, Dendreon reported that there was a significant risk that it would not be able to pay off or refinance its $620 MM debt and that restructuring moves could result in leaving current stock holders with little or no financial ownership. The stock is trading at $1.40; when Provenge was approved in April of 2010, the stock was over $50 per share.
Zytiga and Xtandi happened. The former was approved on April 28, 2011, the latter on August 31, 2012. The former is a tablet, the latter a capsule – both come in bottles after straightforward synthesis and manufacturing processes. Both of these drugs have mechanisms of action that are similar to the mainstays of prostate cancer treatment for many years – androgen deprivation. Why is that important? Because physicians know all about androgen deprivation; they know how to talk to patients about it. Zytiga and Xtandi required no “missionary work.” But Provenge does.
Provenge was the first immunotherapy of its kind – an autologous dendritic cell cancer vaccine pulsed with a fusion protein of prostatic acid phosphatase and GM-CSF. This product was a breakthrough in every sense of the word. However, being on the cutting edge means bleeding edge – doctors did not know what to expect from Provenge, how to talk to patients about Provenge, and how to incorporate Provenge into their anti-androgen armamentarium. Also, the process for treating a patient with Provenge is quite complex – take a lot of blood, ship it off for processing, re-infuse it when it returns. Provenge also is associated with different side effects than androgen therapy, therefore, doctors needed to get comfortable with that.
So, despite the fact that Provenge works well and the Dendreon’s financial performance is favorable (Provenge revenues up and net loss down significantly versus the same quarter in 2013), the company is in great peril thanks to the FDA delay in approval. In that 2 year period, two new competitors literally ate its lunch!
1. March 2007 – FDA Advisory Committee panel recommends approval of Provenge because it extended survival even though it did not show objective response (PSA decrease or reduced size of cancer metastases);
2. May 2007 – FDA rejects Provenge, not understanding that the immunotherapy mechanism of action is consistent with increased survival (by keeping the cancer at bay) without showing signs of cancer regression;
3. April 28, 2009 – 512 patient Phase 3 study confirms improved survival time of Provenge seen previously;
4. April 29, 2010 – Provenge approved by FDA
What would have happened if Provenge were approved, as per the recommendation of the Advisory Committee in 2007? With a 4 year head start on the competition, Provenge would have been firmly entrenched. The company would have not wasted money fighting with the FDA and repeating a study that was not needed. Dendreon would not have needed to take $620 MM in debt to launch the product. The company may have been able to attract a partner or acquire other products to put in its portfolio. It may have also developed other innovative cancer products based on its novel dendritic cell cancer vaccine approach.
So here is the tragic lesson – even when you beat the anti-innovation agenda of the FDA, the time, money, investor good will, and energy lost takes a toll on the company. In the case of Dendreon, the toll may be the end of the company, as last year it announced the search of an acquirer.
Dendreon inspired the success of many other immuno-oncology approaches, including CAR (chimeric antigen receptor) T-cells, which are showing incredible results.
Americans need to wake up – we need to stop the FDA’s anti-innovation agenda or there will simply be no more game changing quantum leaps forward.