Biotech Strategy Blog

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

Posts tagged ‘New Prostate Cancer Drugs’

2012 Annual meeting of American Association for Cancer Research in Chicago. Photo Credit: Pieter DroppertAs Sally Church, PhD noted on Pharma Strategy Blog, the 2012 annual meeting of the American Association for Cancer Research (AACR), recently held in Chicago, showcased many new cancer products in early development.

Cancer new products have a high attrition rate as they move through the development pipeline, so any promising results seen in early stages of development must be viewed with caution.

Results from laboratory studies using cell lines or trials in animals do not always translate into new drugs that work in man, e.g. they may have an unacceptable toxicity, not target the driver mutation, or adaptive resistance may just lead to the cancer bypassing the blocked pathway.

However, scientific meetings such as AACR do provide a window into the possible new drugs of the future. One prostate cancer new product that caught my attention at AACR 2012 as one to watch is AZD3514.

Sarah Loddick from AstraZeneca gave one of the few oral presentations at AACR on this exciting new compound.  This was the only AACR session I attended where I was able to access wifi. Some of my live-tweets are captured in the Storify below (click here to access this on Storify):

http://storify.com/3nt/aacr-2012-azd3514-in-prostate-cancer

Unfortunately, Sarah Loddick has not (as of time of writing) shared a copy of the AZD3514 prostate cancer poster that she presented later in the meeting, so I’m unable to write more about the preclinical prostate cancer data.

AZD3514 is a novel selective androgen receptor down-regulator (SARD) and has a different mechanism of action to drugs such as enzalutamide (MDV3100) that functionally inhibit AR signaling by binding to the AR & AR splice variants.

Sarah Loddick concluded at the end of her oral presentation that AZD3514:

  • inhibits prostate cancer growth in vitro & in vivo
  • has activity against wild-type and mutated AR
  • has activity in pre-clinical models that represent castration resistant prostate cancer (CRPC)
  • inhibits seminal vesicle growth in rats in the presence of physiological levels of circulating tumor cells.

AZD3514 is in a multi-center phase 1 clinical trial in patients with metastatic CRPC in Europe (NCT01162395) and Japan (NCT01351688). I look forward to seeing the presentation of the results from these trials.

From what I saw at AACR, AZD3514 is a new prostate cancer drug to watch.

Update April 20, 2012

I was delighted to receive an email this morning from Sarah Loddick of AstraZeneca with a copy of the AZD3514 poster that I requested (AACR abstract #3848): “Pre-clinical profile of AZD3514: a small molecule targeting androgen receptor function with a novel mechanism of action and the potential to treat castration resistant prostate cancer.

I am sensitive to the unpublished status of much of the research presented at AACR, but without giving too much away, some of the key messages from this poster are that AZD3514:

  • Binds to the androgen receptor (AR) ligand binding domain & reduces viability of prostate cancer cells in vitro. 
  • Inhibits AR transcriptional activity within 2h of exposure in LNCaP cells, and reduced both PSA & TMPRSS2 mRNA
  • Inhibits AR induced translocation to the nucleus
  • Causes AR down-regulation in prostate cells in vitro
  • Causes AR down-regulation in rat R3327H prostate tumors
  • Has activity in pre-clinical models of CRPC

A drug such as AZD3514 in prostate cancer could potentially be used to overcome resistance to enzalutamide (MDV3100), or alternatively it could be used ahead of enzalutamide if it has the potential to avoid resistance and offer better outcomes. We obviously will have to wait for clinical data to see what it’s true potential is and the data from AACR, while promising, is still only preclinical.

The prostate cancer market is a busy one and companies with AR targeted new products in development will have to offer drugs that are superior to enzalutamide if they wish to have lasting commercial success.

Update June 6, 2013: AstraZeneca terminates development of AZD3514 in Advanced Prostate Cancer

At ASCO 2013 it was announced that the development of AZD3514 in advanced prostate cancer has been terminated. You can read more about what happened in the first-in-human clinical trial in my AZD3514 blog post from ASCO 2013.

1 Comment

View-of-Paris-from-European-Association-of-Urology-2012-CongressToday sees the start of the 27th annual European Association of Urology (EAU) Congress at the Palais des Congrès in Paris.

The meeting runs from 24-28 February, 2012. Over 10,000 delegates are expected, and more than 1193 abstracts have been accepted for poster and video sessions.

In addition to a scientific programme, this meeting also has a strong educational component with numerous courses through the European School of Urology (ESU) and hands-on-training to improve surgical skills in cooperation with the EAU Section of Uro-Technology (ESUT), the EAU Section of Urolithiasis (EULIS) and the EAU Section of Robotic Urology (ERUS).

If you can’t be in Paris, then EAU have some live webcasts and they will be sharing a lot of the content from the meeting as well as undertaking video interviews.  Check out the EAU 2012 Paris Congress website for more information.

For those that are interested in following the twitter coverage of the meeting, the hashtag is #EAU12, and EAU is @uroweb on twitter.  You can also use the twitter aggregator below:

 

I will be flying to Stockholm next week for the European Multidisciplinary Cancer Congress (twitter #EMCC2011), more commonly known as ECCO or ESMO 2011.

What are the sessions that look interesting at the meeting? I previously wrote about the phase III ALSYMPCA trial data for Alpharadin that will be presented as a late breaking abstract.

In addition, the best abstract at ECCO 2011 is on vismodegib in basal cell carcinoma.  Sally Church on Pharma Strategy Blog has written extensively about the hedgehog pathway and role of smoothend inhibition in the treatment of cancer.

What else has attracted my attention at ECCO 2011 in Stockholm? In looking at the preliminary program I was struck by the large number of scientific symposia throughout the meeting. However, many occur at the same time! On Saturday 24th two in particular caught my attention:

Molecular Imaging of Hypoxia

Nanotechnologies for Targeted Drug Delivery

Having written about hypoxia and nanotechnology on this blog, I will probably go to one of those two sessions.

Later in the conference, there is another block of scientific symposia on Monday 26th, again all at the same time! Several that look particularly interesting include:

  • How to understand and to Reverse Drug Resistance in Metastatic Breast Cancer
  • From New Targets to New Drugs in Prostate Cancer
  • Tailoring Personalized Medicine for the Future
  • The Role of IGFs/IGF-1R Pathway in Paediatric Malignancies

And in case one still hasn’t had enough science, there’s another group of scientific symposia on the final day of the conference on Tuesday, 27 September including:

  • Unravelling Ras PI3 Kinases Targets 
  • PARP inhibiting strategies: from Molecular Mechanisms to Rational Clinical Applications

I expect Stockholm to be expensive, they jokingly say you can buy a brewery in America for the price of a beer in the city, but it looks like there’ll be some interesting news and scientific data from the meeting. Hopefully I’ll have a few hours sometime to see something of what looks like a stunningly beautiful city.

If you plan to be in Stockholm do let me know. I can be reached via twitter (@3NT).

error: Content is protected !!