Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘Prostate Cancer New Treatment’

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.

I am off to Washington DC tomorrow for the annual meeting of the American Urological Association (AUA).

If you are not able to attend, then you can follow the Twitter coverage on Pharma Strategy Blog where Sally Church (@MaverickNY) will be aggregating the tweets.  The conference hashtag is #AUA2011.  I also expect to be live-tweeting from the conference.

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Like many medical conferences in the United States, the AUA meeting kicks off with independent continuing medical education (CME) satellite symposia on topics of interest.

As a lawyer who has to pay for his own continuing legal education (CLE) credits, I have to confess that I am somewhat cynical that other professionals such as physicians expect to have their CME paid for through free industry-sponsored events.  These symposia are certainly not cheap to run.

However, compared with Europe, CME events in the United States are usually well-produced and fair balanced, albeit with a topical theme that obviously relates to the sponsor’s interest.

The two satellite symposia that I will be attending at AUA are Friday evening’s Amgen supported “Managing Skeletal-Related Events in Patients with Prostate Cancer” and the Saturday morning Astellas/Medivation supported “Reason for Hope: Key Advances in the Management of Castration-Resistant Prostate Cancer.”

While at Quintiles, I was lead CRA/European Project Manager for the phase III trial trial of risedronate in elderly women at risk of hip fracture, so I am interested in bone related treatments, and am looking forward to hearing more about denosumab (Xgeva®) and its impact on skeletal related events (SRE).

Oliver Sartor (Tulane) raises some excellent questions in a recent paper published in the Asian Journal of Andrology, “if a patient has a SRE, does it affect the way a patient feels, functions or survives?”

Sartor argues that a better definition of the benefit a drug has on SRE’s would be “a reduction in pain, analgesic consumption or improvement in quality of life (QoL)” instead of the current “feel, function or survive” standard.

He notes that patients with bone-metastatic castrate resistant prostate cancer (CRPC) have a limited life expectancy, so that QoL is a key issue. “An asymptomatic event linked to a future adverse event is less meaningful in a patient with metastatic CRPC.

Sartor concluded his paper by saying:

“The lack of effect of bisphosphonates or denosumab on patient-reported outcomes including QoL, pain or analgesic consumption continues to be a disappointment for this entire field.”

When we talk about a reduction in SRE’s what does this really mean for the patient?  I look forward to hearing what the expert panel at Friday evening’s symposia on this topic and hope it will be addressed.

Moving on to the other satellite symposium, supported by Medivation/Astellas, that I will be attending early on Saturday morning.  I expect this symposium will focus on new drugs in the pipeline such as MDV3011 and ARN-509 that target the androgen receptor. Hopefully they will also discuss other therapeutics, such as the recently approved abiraterone acetate (Zytiga®), as well TAK-700, which has a similar mechanism of action to abiraterone, i.e. they both inhibit CYP17 and testosterone production.

I’m looking forward to hearing what the expert panel has to say about the need to take prednisone with abiraterone, and whether there are any issues surrounding long-term usage if abiraterone ends up being used earlier in the pre-chemotherapy setting.  Updated data from the COU-AA-301 trial will be presented at AUA on Monday, and I expect a lot of interest from urologists in this.

The satellite symposia are set to be a good warm up act to the start of the main AUA meeting that runs from May 14 to 19 in Washington DC.  I’ll be writing more from the AUA 2011 over the next few days.

ResearchBlogging.orgSartor, O. (2011). Denosumab in bone-metastatic prostate cancer: known effects on skeletal-related events but unknown effects on quality of life Asian Journal of Andrology DOI: 10.1038/aja.2011.33

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