Medivation investors hoping for a windfall will be disappointed to hear that on December 20, 2012 a California judge ruled
One of the late-breaking abstracts (not yet published) that I am looking forward to at the forthcoming annual Congress of the European Society for Medical Oncology (ESMO 2012) in Vienna is on ODM-201 (Orion Pharma):
LBA25-PR: ARADES trial: A first-in-man, open-label, phase I/II safety, pharmacokinetic, and proof-of-concept study of ODM-201 in patients (pts) with progressive metastatic castration-resistant prostate cancer (mCRPC)
ODM-201 is a new antiandrogen from Finnish company, Orion Pharma, and is being developed in partnership with Endo Pharmaceuticals (NASDAQ: ENDP).
Prostate cancer is the second leading cause of cancer death in men, so it was good news this morning when Medivation & Astellas issued a press release that showed positive data from the phase 3 AFFIRM trial for MDV3100.
MDV3100 produced a 4.8-month advantage in median overall survival compared to placebo.
The estimated median survival for men treated with MDV3100 was 18.4 months compared with 13.6 months for men treated with placebo.
MDV3100 provided a 37 percent reduction in risk of death compared to placebo (Hazard Ratio=0.631).
To put the 4.8 month survival advantage in context, this compares favorably with 3.9 months for abiraterone (Hazard Ratio =0.646), in the COU-AA-301 trial.
Positive data was expected given the sound scientific rationale behind MDV3100 and the preliminary data (abstract 4501) presented at the ASCO annual meeting this year. J Clin Oncol 29: 2011 (suppl; abstr 4501).
The drug has a high affinity for the androgen receptor (AR) that is highly expressed on prostate cancer cells. You can read an excellent interview on Pharma Strategy Blog with Charles Sawyers, who was one of the co-inventors.
MDV3011 blocks the androgen receptor (AR) from moving into the nucleus and activating growth genes and is a more complete inhibitor of AR than bicalutamide.
One hot topic of conversation at ASCO was the potential to combine MDV3100 (androgen receptor blocker) with abiraterone acetate (Zytiga) (androgen synthesis inhibitor), thereby shutting down upstream and downstream activity of the driving receptor in advanced prostate cancer. The scientific rationale for this appears sound, so it is likely that a combination clinical trial may well be done to test this hypothesis at some point in the future.
MDV3100 has a significant advantage over abiraterone acetate (Zytiga) in that concomitant steroids are not required. Daily steroids have their side effects. Urologists in particular will be attracted to MDV3100 and its ease of use.
Clinical trials in prostate cancer are ongoing with a multitude of new emerging therapies including TAK-700, Cabozantinib (XL184), radium-223 chloride (Alpharadin), BPX-101, Prostvac-VF, ipilumumab, Custirsen (OGX-011), dasatinib (Sprycel), lenalidomide (Revlimid) and ARN-509 to name but a few.
It is a therapeutic area with a lot going on after very little activity for a decade. The positive interim data for MDV3100 announced today is good news for prostate cancer patients, and we await presentation of the data next year.
Medivation and Astellas plan to hold a pre-NDA meeting with the U.S. Food and Drug Administration (FDA) in early 2012, so US approval could be possible later next year.
The market for prostate cancer therapies is set to expand from $1 billion currently to $5 billion by 2015, according to analysts reported by this morning’s Washington Post/Bloomberg news. This is perhaps no surprise given the recent approval of abiraterone acetate (Zytiga®) from Ortho Biotech (JNJ).
New clinical data on prostate cancer clinical trial results is expected at the 2011 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago this weekend from many of the prostate cancer therapies in development such as MDV3100, TAK700, ARN-509, cabozantinib (XL184), ipilimumab, custirsen (OGX-11), BPX-101, alpharadin, denosumab (Xgeva®) and Prostvac-VF.
Indeed, one could argue that prostate cancer is becoming a competitive marketplace. Any emerging biotechnology company that is not already developing a prostate cancer drug is likely to find it a hard market in which to create a blockbuster. By the time any drug comes to market, there will be incumbents with effective products who have captured market share.
Prostate cancer is an exciting market to watch from a marketing strategy and patient perspective, as several companies potentially bring new products to market over the next few years.
However, the bottom line is that patients will live longer as a result of all the innovation that is taking place. Not only that but physician education and awareness of how to treat this disease is also likely to improve as they seek out knowledge on new therapies and treatments. This to many will make a major difference. At the recent American Urological Association (AUA) annual meeting, the sessions on treatment of prostate cancer were standing room only. There is clearly a demand for knowledge out there as the treatment paradigms change.
At the other end of the spectrum, there is also innovation taking place in terms of improved diagnosis and treatment of prostate cancer. Whether we should screen all men for PSA remains a controversial topic, although use of risk calculators do appear to offer less false positives. Indeed, calculating risk is going to be one of the key areas that primary care physicians and urologists need to focus on, particularly in the light of the PIVOT trial data that was presented at AUA, showing radical prostatectomy (with risks including incontinence and erectile dysfunction) was not better than watchful waiting in low-risk, early stage disease.
However, a presentation I am looking forward to at ASCO 2011 is on circulating tumor cells (CTC) and whether these can be a prognostic or even a predictive biomarker. Both the phase III MDV3100 and abiraterone acetate clinical trials captured CTC data. It will be exciting news at ASCO 2011 if circulating tumor cells that require only a blood sample offer an improvement over PSA not only for detection of prostate cancer, but in monitoring the disease over time.
I will be at ASCO 2011 this weekend, and look forward to writing more on prostate cancer from the conference!
The 102nd Annual meeting of the American Association for Cancer Research (AACR) ended yesterday in Orlando, and it was only the diehards who kept going till the last session of the last day for an update on “Novel Androgen Receptor Antagonists.”
As I mentioned in an earlier post, there is a lot of excitement in the prostate cancer field at the moment with three new therapies approved last year (cabazitaxel, sipuleucel-T, denosumab), and more expected over the next two years (abiraterone acetate, MDV3100, cabozantinib/XL-184).
What I took from the AACR session I attended, is that there are also other products in the pipeline that are worth watching. Below is a list of some of the products that were mentioned. It’s not intended to be a comprehensive review of the prostate cancer landscape, only my notes and thoughts on some of the new products that the speakers touched upon.
Abiraterone Acetate: The postive phase III trial results were reported last year at ESMO and ASCO GU, and the approval of this drug is currently being considered by the FDA. Approval is expected shortly, and possibly in time for launch at the forthcoming annual meeting of the American Urological Association (AUA) meeting in Washington, DC.
Abiraterone (brand name Zytiga) inhibits the enzymes (17-alpha hydroxylase and C17, 20 lyase) responsible for adrenal androgen formation.
The phase III results were impressive in very sick patients who were close to the end of their lives in very advanced disease. Overall survival increased from 10.9 to 14.8 months in the second line chemotherapy setting post docetaxel. It’s expected that the results will be more dramatic pre-chemotherapy.
Once the FDA approval is obtained, it’s hard to see how oncologists will not consider abiraterone instead of cabazitaxel in the second-line chemotherapy setting. An easily taken pill with fewer less side effects may be a more convenient option for elderly or frail men with prostate cancer. Abiraterone’s approval will not be good news for sanofi-aventis.
I also expect we will see significantly off-label usage of abiraterone pre-chemotherapy by urologists as they seek to maintain hormone-sensitivity in their patients after several lines of anti-hormonal therapies. There is a phase III trial ongoing in this setting that is expected to show promising data by the end of the year.
However, it’s a good strategy to come market as soon as possible to provide wider access to patients in need, and the post-docetaxel second line setting allowed the overall survival benefit to be shown before the pre-chemo data would be available.
However, what I learned at the meeting is that abiraterone acetate may not be the best product in the long term. Currently it requires the corticosteroid, prednisone, to be given at the same time to attenuate the mineralocorticoid effects. Questions that were raised in the AACR session about long-term treatment with abiraterone included, “Must a corticosteroid be given concurrently?” and “What about hypertension?”
Other questions remain, such as possible development of resistance to abiraterone. Often the first drug to market is not the best, and it’s possible that second generation new products in the pipeline may be better than abiraterone and delay the time to resistance further.
However, what abiraterone does have is first mover advantage and depending on the pricing strategy adopted by Johnson & Johnson, the ability to capture market share earlier. It will be interesting to see what happens with this drug, but it’s certainly an exciting time for patients with prostate cancer.
TAK-700: This drug from Takeda/Millennium is a more potent inhibitor of C17α-hydroxylase than abiraterone. One of the panelists at AACR believed that TAK-700 “may in the long run surplant abiraterone acetate due to less need for mineralocorticoids.” TAK 700 entered phase III clinical trials late last year.
MDV3100: This drug is being developed by Medivation/Astellas and is also in phase III trials, with data expected by the end of this year or early 2012. It has a high affinity for the androgen receptor. However, what came across in the AACR presentation by Howard Scher, was his view that the second compound developed by Charles Sawyers, ARN-509 may be better than MDV3100.
ARN-509: This drug from Aragon Pharmaceuticals is in phase I/II clinical trials and is definitely one to watch. As Dr Scher pointed out, ARN-509 is more potent than MDV3100 and I expect we will see publication of more data on ARN-509 in the near future.
If you are interested in prostate cancer, AACR are offering webcasts and podcasts of scientific sessions this year. Further information can be found on their website. AACR have also announced a scientific special session on “Advances in Prostate Cancer Research” from February 6-9 2012. It’s certainly an interesting and exciting time in this field as new products become available, something that is likely to make a real difference to how this disease is treated.