Pharma Strategy Blog

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Posts tagged ‘AUA’

At the annual American Urological Association (AUA) meeting this week in Washington DC, Dr Matthew Smith from Mass General Hospital presented updated data from the phase III 147 trial comparing denosumab to placebo in managing skeletal related events (SREs) and bone metastases-free survival.   Skeletal complications are a major cause of prostate cancer morbidity.

The results were somewhat controversial, however, because while surrogate measures such as delaying time to SREs clearly show a benefit in favour of denosumab, no difference in overall survival was seen over placebo.

To find out whether these measures are clinically meaningful or not, I chatted with Dr Neal Shore, a urologist who is the Medical Director of the Carolina Urologic Research Center in Myrtle Beach, South Carolina as part of the ongoing Making a Difference series of interviews.

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Today it’s Friday 13th and we’re heading off on the road again, this time to Washington DC for the much anticipated annual meeting of the American Urology Association (AUA).

We’ll be covering the hot topics on urologic cancers, including bladder and prostate cancers and renal cell carcinoma (RCC). I’m particularly interested in castrate resistant prostate cancer and updates on the abiraterone (Zytiga) data following the recent approval post chemotherapy in the US, and also the long term data for Medivation/Astellas’ MDV3100 from their phase I/II trial. It’s always important to know how patients in the early trials are doing.

We will post various updates here on Pharma Strategy Blog over the weekend including blog posts, podcasts and of course, video highlights. Do check back daily for news and snippets about what’s hot here at AUA.

In the meantime, you can also follow the aggregated tweets from the attendees – if you have a question, please don’t hesitate to ask me on Twitter (@maverickny) using the offical conference hashtag #aua2011 or in the blog comments below:

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Getting back to the blogging groove after 3 weeks on the road at successive conferences (AUA, ASCO and EHA) is a bit of a shock, so the first post will be short and pithy.

AUA will be remembered for incredibly unsocial and early 6am education session starts.  No thanks, with three meetings in a row stamina trumps insanity by a long shot.  At ASCO, the Chicago venue is sprawling with long walks between sessions that appear to have no theme or cohesion around them and of course, the Press Room is way out in left field over the walkway no matter where you need to go.  The S406 Vista Room was particularly bad and became notorious for the #blisterwalk on Twitter.  Never again will I complain about switching between Halls A and F at Orlando, that's a piece of cake by comparison!

The second big difference I noticed between US and EU meetings was the presence or absence of chotchkes.  In the US they are now verboten of course, but the EU has no such constraints.

Now, I'm not sure a branded laptop sleeve or a Post-it pad ever made a difference to prescribing habits, but well done journal reprint carriers with a clear summary of the data do make a difference in oncology.  They help reinforce the efficacy, survival curves and key messages to your audience.

One thing I particularly remember most from EHA was a very well done piece that clearly differentiated the brand from the competitor, with data I hadn't noticed before.  Talking to some of the hematologists, they were equally interested in the pieces too as they included a peer reviewed journal reprint.  Some were taking copies back to share and discuss the data with their colleagues, which I found interesting.  What's going to have more impact – a branded item with no message or a clinical paper?

The Roche booth was particularly busy whenever I visited the exhibits.  The reason?  Great espresso coffee and the best quality nibbles, much appreciated early in the morning and late afternoon by drooping attendees.  I was less enthused by the aggressive ladies on the stand who wouldn't let me play with the interactive education quizzes for a USB key because the press passes didn't have a bar code on them.  I desperately needed a USB key to share a file with a physician.  We both walked away from that with a negative impression that overrode the nice refreshments.  A little flexibility goes a long way.

The other neat thing at the European Hematology Association meeting in Barcelona was a CD of many of the biology and clinical posters.  Great stuff, saves hours of work trying to piece together snippets taken on an iPhone!

Perhaps my favourite thing about European meetings, aside from the relaxed sociable hours with time to network with people, was the integration and inclusion of the patient advocate voice.  Critical, but largely ignored in American meetings.  More on this in another post.

This week I'll be putting up some synopses of data found interesting from the meetings, but the analyses may well be very different from what you saw in the news items.  Some of the reporting at ASCO in particular was sketchy puff pieces or hype at best, with very little real understanding of what the data actually means.

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It's been an interesting time here in San Francisco at the American Urology Association (AUA) meeting. Mostly, I've attended prostate cancer sessions to get both a breadth and depth perception of what's going on this cancer type.  

My focus is very much therapeutic development, so here are three key trends that I've noticed at the 2010 AUA meeting:

  1. PSA is not a brilliant biomarker, but it's all we have for now.
  2. Androgen ablation is not permanent.
  3. Immunotherapy is a hot new topic.

What alternatives are there to PSA?

An abstract today from the Colorado Cancer Center suggested that PCA3 may offer a urine based genetic assay for detection of prostate cancer in men with elevated levels of PSA. PSA can offer false positive results and up to 75% men with prostate cancer have a negative biopsy. This new approach sounds promising. PCA3 is overexpressed in more than 90 percent of prostate cancers and the gene overexpression is specific to prostate cancer.  It has been linked to more accurate prediction of positive biopsies compared to PSA, and it is easy to test in urine samples following a digital rectal exam of the prostate.

Presumably it may turn out to be more accurate than PSA and perhaps offer a better way to detect either the actual disease earlier or more aggressive disease earlier.  The test was developed by GenProbe and is not yet approved by the FDA, but a new test to watch out for.

Androgen ablation therapies are not particular effective

Often times, testosterone levels rise above the minimum castrate level after about a year.  Ultimately, more effective androgen receptor antagonists are needed, hence the significant interest in this meeting in abiraterone and MDV3100, two new antagonists in phase III development.  Long term use of androgen deprivation is also inevitably associated with side effects, which have not been well appreciated until recently.

The approval of Provenge gives hope that survival can be extended without drastic side effects

Pharma companies in the oncology space would do well to realise that sick people with cancer don't want to be reminded of such and most certainly do not want a 'relationship' with a brand.  This is not Nike or a FMCG brand offering coupons and offers.  What most people do want is less side effects and better efficacy without having to trade them off.  

Now that we have a proof of concept poster child in Provenge in a solid tumour, we can also see that it may ultimately offer a way to combine newer hormonal therapies with a vaccine to offer men a more effective tool against their disease, delaying the time not only to progression, but also to metastases and chemotherapy.

Other immunotherapies are also being evaluated in prostate cancer, including ipilimumab (BMS), an anti-CTLA4 inhibitor and ProstVac, a cancer vaccine.  More on ipilimumab in another blog post but having had a few queries as to what ProstVac is, here's my basic take on it.

ProstVac differs from Provenge in that it requires 7 infusions over a 6 month period as opposed to 3 within the first month.  My understanding is that it is a sequentially dosed combination of two different Poxviruses which each encode prostate specific antigen (PSA) plus three immune enhancing co-stimulatory molecules, B7.1, ICAM-1, and Lfa-3 (TRICOM). The first Poxvirus is Vaccinia-PSA-TRICOM, which is replication competent and is good for immune priming. The second Poxvirus is Fowlpox-PSA-TRICOM, a non-replicating virus, which is good for repetitive immune boosting.  In some ways, it seeks to achieve the same end as Provenge (T-cell stimulation) but via a slightly different approach.

What's next?

More on prostate cancer at the American Society of Clinical Oncology (ASCO) meeting next week!

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Past American Urological Association (AUA) meetings have seen a lot of same old, same old with very little that is new in the way of truly innovative and exciting new developments.  In many ways, prostate cancer is the male equivalent of ovarian cancer, with pharma companies considering it after the breast, lung and colorectal cancers, despite prostate cancer being fairly large in terms in epidemiology, from a pure numbers perspective.

Why is this?

Firstly, we need to consider the natural course of the disease, which unlike breast and lung cancers, is fairly indolent.  Men diagnosed early with prostate cancer can live for 10-15 years, often with long periods of watchful waiting, making adjuvant trials necessarily long ones.

Secondly, once hormonal therapy begins to enable castration and reduction in the levels of testosterone that drives the cancer's growth, patients are seen and managed by urologists, who prefer to treat with oral therapies.  Until recently, Pharma focused very much on intravenous infusions designed for oncologists and never the twain really met in the middle.

Thirdly, traditional drug development for chemotherapy begins in the latest stage of treatment after failure of existing therapies (typically 2nd or 3rd+ line) and moves earlier up the disease stage in a classic niche by niche development strategy.

These factors combine to essentially create 3 distinct, albeit crude, phases of treatment for prostate cancer:

  1. Watchful waiting
  2. Androgen deprivation therapy (ADT)
  3. Chemotherapy for stage IV metastatic disease

How are things changing?

Dendreon recently received approval for their autologous cell vaccine, sipuleucel-T (Provenge) in asymptomatic metastatic castration resistant disease, meaning that in men where hormonal therapies cease to work but have some early evidence of metastatic disease, now have a completely new and relatively non-toxic therapeutic option prior to chemotherapy with Taxotere, mitoxantrone or even prednisone.

Much has been written about the potential for vaccines earlier in the disease when the tumour burden is much lower, so hopefully we will see some future exploration in this area now that the proof of concept for the first commercial cancer vaccine exists and Dendreon will have more funds to reinvest in R&D as revenues are generated.  They have a real opportunity here.

Past studies with docetaxel (Taxotere) have shown an improved survival benefit of 2.4 months over prednisone alone in androgen independent (hormone refractory) population that was essentially symptomatic.  Two phase III Provenge studies reported a median survival benefit of 4.1 and 4.5 months respectively, meaning that 50% of the men did better and 50% did worse than 4-4.5 months. 

There are now at least 8 other compounds in phase III development for the treatment of advanced prostate cancer.  One of these, sanofi-aventis' cabazitaxel (Jevtana) has already been filed and DDMAC review is expected in the summer, meaning the drug could possibly get approval in the 2nd-line setting after Taxotere by September in an area of high unmet need since there are few options available in this setting.  The data is expected to be presented at ASCO next week, so more on that then.

So now we have two potential therapeutic options before and after Taxotere in 2010 alone, which is progress indeed.

What other compounds are there?

There are a number of agents that I like. Cougar and J&J's abiraterone is probably the most advanced. It is an inhibitor of 17,20 lyase that essentially throttle testesterone production in the testes and adrenal glands.  Millennium-Takeda also have a similar compound in earlier development called TAK700.  The two appear to differ in that one is steroidal and the other is non-steroidal, but whether this will make any meaningful difference isn't yet clear.  Time will tell.  

The abiraterone trials are not scheduled to complete until mid 2011 at the earliest, so assuming the data is positive, approval likely won't happen until the 2nd half of 2012, giving Dendreon a two year commercial advantage over the competition, who are mostly testing their compounds in the post Taxotere setting, at least initially.

Perhaps the most exciting agent from a biology perspective is MDV3100 from Medivation/Astellas, which I have written extensively about in past blog posts.  Essentially, the current androgen blockers are fairly ineffective at controlling aggressive disease so a more complete inhibitor of the Androgen Receptor (AR) may offer a better chance of making an impact.  Medivation have quickly realised that their real opportunity may well be either after hormonal therapies, in combination with them, or perhaps even in place of them earlier in the disease and have announced several new phase II and III trials will commence later this year.  Astellas have significant advantage over J&J as a partner since they already have a strong urology franchise, which is vitally important going forward.

Several other therapies interest me too, but they will be the subject of another blog post later during this meeting as the mutations and critically expressed pathways as the disease progresses may well drive future therapeutic interventions.

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On Friday, I'm heading off to the annual American Urology Association (AUA) meeting in San Francisco and looking forward to catching up on the hot topics in prostate and renal cancers.  

image from www.flickr.comIt promises to be a good meeting this year with lots of new data expected from a number of marketed products, newly approved products and of course, products in development.

I'll be tweeting snippets from the meeting under the hashtag #AUA2010 as some attendees are already actively using that one.  Unfortunately, #AUA already seems to be used for something else, which is a shame as those extra 4 characters make a huge difference on Twitter!

More to follow at the meeting, where I'll summarise some of the key findings over the weekend as they are published.

If you're attending the event and would like to meet up, please contact me either via email or via Twitter - it's always fun to meet people in real life!

Photo Credit: Alain Picard

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