As I commented last week, cancer statistics are both staggering and disappointing. Although cancer deaths per 100,000 people have been on the downswing since 1991 thanks to access to more effective medications and better awareness about the negative health effects of smoking, there is still a lot of research and progress yet to achieve. My focus in this 12-week series is to bring to light both the need for continued research in these fields, as well as highlight ways you can profit from the biggest current and upcoming players in each field.
The skinny on prostate cancer
To start off, we're going to take a look at prostate cancer, the cancer most expected to be diagnosed in 2013, with 238,590 projected cases, according to the National Cancer Institute. Considering that prostate cancer is expected to be attributed to 28% of all male cancer deaths this year, it's an area of intense ongoing research.
So far we've seen incredible improvement in the underlying data, but we're nowhere near the desired result as of yet. Data from the American Cancer Society (link opens PDF) demonstrates that better detection and medication has moved the five-year survival rate in the 1975-1977 time period from just 68% to a figure approaching 100% in the 2002-2008 period. Even long-term survival rates are strong based on the most recent data, with 10-year and 15-year survival rates of 98% and 93%, respectively. Understandably, there's some margin of error to these figures, but it nonetheless shows marked improvement in detection and treatment of the disease.
Most cases of prostate cancer are caught in a localized, non-metastasized state, which makes it often more easily treatable than other cancers and leads to the increased survival rate figures that ACS has noted in recent years. Although there's no specific one-size-fits-all treatment for prostate cancer, hormonal therapy, radiation, chemotherapy, surgery, or a combination of these four treatments, is often used. In cases where smaller or less aggressive tumors are present, sometimes even a watch-and-wait approach is taken.
Let's have a look at some of the biggest players in prostate cancer, as well as some of the upcoming therapies that could revolutionize treatment potential.
Where investment dollars are headed
The real investment dollars in prostate cancer are being spent on the advanced or metastatic stages of the disease where the patient has stopped responding to the first-line hormone and chemotherapy medications. Prior to 2004, only docetaxel had been shown to improve overall median survival in advanced stages of the disease; now metastatic-resistant prostate cancer suffers have hope in the following four medications:
- Zytiga -- Developed by Johnson & Johnson (NYSE:JNJ), Zytiga is an oral medication that was approved in April 2011 to be used in combination with prednisone as a second-line advanced prostate cancer treatment. The pill targets a protein that plays an important role in producing testosterone, a hormone shown to cause prostate cancer tumor growth. Zytiga practically eliminates all testosterone production and, therefore, slows prostate cancer growth dramatically. In clinical trials, the Zytiga/prednisone combination extended median overall survival to 14.8 months from 10.9 months for the placebo/prednisone combo. A few months following its approval, this median survival benefit was upped from 3.9 month to 4.6 months by J&J. More recently, in December 2012, Zytiga was approved for earlier use (i.e., before chemotherapy has been administered) after a 1,088 patient study that showed chemotherapy-naive patients on Zytiga had a median survival time of five months longer than those on the placebo.
- Xtandi -- Described as a "once-in-a-blue-moon approval" by the Fool's Brian Orelli, Xtandi, developed by Medivation (NASDAQ:MDVN) and Astellas Pharma, was approved three months early by the FDA after the oral pill -- which, like Zytiga, targets male testosterone levels -- improved median overall survival to 18.4 months from the 13.6 months witnessed with the placebo. One noticeable difference between the two drugs as pointed out by The New York Times, which may give Xtandi an edge, is that it doesn't need to be given in combination with prednisone to lessen its side effects, unlike Zytiga. On the flip side, at $5,500 per month, Zytiga is noticeably cheaper than Xtandi,which runs $7,450 per month.
- Provenge -- When cellular immunotherapy treatment Provenge, developed by Dendreon (NASDAQOTH:DNDNQ) was approved in 2010, it was expected to change the face of advanced prostate cancer treatment. The three-course treatment involves removing immune cells from a patients' blood, exposing them to a commonly found cancer protein, and then reinjecting them into the patients' prostate with the expectation that they'll attack the prostate cancer cells. In clinical trials, median overall survival time rose 4.1 months to 25.8 months versus 21.7 months for the placebo. Unfortunately for Dendreon, sales have lagged because its $93,000 price tag has made physicians and patients leery of potentially not being reimbursed. Insurers, as well, have been slow to latch onto the treatment.
- Jevtana -- Sanofi's (NASDAQ:SNY) Jevtana, an IV-administered chemotherapy that's combined with prednisone, has largely been pushed to the back burner in recent years by Zytiga and Xtandi, but it's still worth mentioning. In trials, Jevtana boosted median overall survival by 2.4 months to 15.1 months. Like Xtandi, Jevtana targets treatment through hormone control and, at the time, was also approved three months early. However, with growing median overall survival times and all-oral medications available, Sanofi's drug has fallen out of favor.
What's coming down the pipeline
Now that we've got an idea of what's already available to treat metastatic castration-resistant prostate cancer, let's have a look at some upcoming treatments that may steal the spotlight in the coming years.
- Cometriq -- Late last year, Exelixis (NASDAQ:EXEL) received its first drug approval in Cometriq for the treatment of metastatic medullary thyroid cancer, or MTC. The drug, in trials, nearly tripled the median overall survival rate relative to the placebo, so I've been very eager to see how this would translate over to other diseases. Currently, Exelixis is recruiting for its Comet-1 and Comet-2 prostate cancer trials utilizing Cometriq for patients as a second, and potentially, third-line, treatment. In mid-stage trials, Cometriq (previously cabozantinib) demonstrated strong growth curbing clinical activity, especially in patients that developed bone metastases.
- Radium-223 dichloride -- Despite sounding like an ingredient to a nuclear bomb, this experimental drug that targets bone metastases in similar fashion to Cometriq and was developed by Bayer and Algeta, is currently under a priority review by the FDA. In trials, Radium-223 improved median overall survival to by nearly three months to 14 months as compared to 11.2 months for the control arm.
Keep in mind that we've also seen numerous disappointments along the way. Pfizer discontinued its study of Sutent for the treatment of prostate cancer in September 2010 after interim late-stage data showed that the drug was unlikely to show a clinically significant benefit when combined with a chemotherapy agent. Amgen's Xgeva, which is designed to prevent fracturing in bones, was denied by the FDA the right to even submit its new drug application for the indication of treating bone metastases occasionally associated with metastatic prostate cancer in April of last year. The key point is that even big pharmaceuticals have a difficult time tackling this disease.
Your best investment
For those willing to really roll the dice, Exelixis' future looks promising given its incredible results in MTC. I've been saying for months that it's highly unlikely that Cometriq would provide such strong statistical evidence for MTC but not translate over favorably to at least a few other disease indications.
For those of you who are looking for a more stable long-term solution, that would have to go to Xtandi. Even though Xtandi's price point is enough to push some physicians and patients to use Zytiga, the simple fact that it doesn't need to be combined with a steroid to reduce its potential side effects makes it the go-to late-stage drug. Decision Resources, a pharmaceutical-based market researcher, is projecting peak sales will hit $2.2 billion for Xtandi by 2021. If these peak sales estimates prove accurate, then Medivation is valued at just 1.6 times peak sales -- a discount compared to some revolutionary cancer therapy highfliers.
Stay tuned next week when we tackle the current and upcoming therapies for the treatment of breast cancer in this tackling cancer series.