Biotech Strategy Blog

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

Posts from the ‘Urology’ category

Immune checkpoint inhibitors that target CTLA4, PD1 and PDL1 can generate prolonged responses in a minority of patients, but the results so far in prostate cancer have been disappointing. Prostate cancer doctors have not been part of the excitement spreading through the cancer community like a “Mexican wave.”

Prostate cancer has not featured significantly in the cancer immunotherapy news recently, but that’s not to say there is not a lot going on. The phase 3 trial results of ipilimumab (a checkpoint inhibitor of CTLA-4) in the pre-chemotherapy setting of advanced prostate cancer (NCT01057810) are expected soon and there is also the eagerly awaited phase 3 trial of the PROSTVAC vaccine (NCT01322490).

Dr James Gulley ASCO 2015

At ASCO 2015, BSB interviewed Dr James L. Gulley, MD, PhD Chief of the Genitourinary Malignancies Branch and Director of the Medical Oncology Service at the National Cancer Institute (pictured above).

He talked about some of the cancer vaccine work he has done as part of the CRADA (Cooperative Research and Development Agreement) between the NCI and Bavarian Nordic, as well as strategies to help immunotherapy work in those tumors such as prostate cancer that are non-inflamed, where there may be an insufficient immune response for checkpoint inhibitors to work effectively.

Readers may recall we interviewed him at ASCO GU earlier year, “How to make non-immunogenic cancer sensitive to checkpoint inhibitors.” His outstanding work could shape the future of prostate cancer immunotherapy.

This post also includes additional ASCO 2015 commentary on from Dr Oliver Sartor, Professor of Cancer Research at Tulane University, who shared his perspective on the ipilimumab and PROSTVAC phase 3 prostate cancer trials that are due to readout soon.

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Medivation-LogoNew Orleans – in today’s plenary session at the 2015 annual meeting of the American Urological Association (Twitter: #AUA15), Dr Celestia Higano (Seattle), presented the results of the STRIVE trial (NCT01664923) – a multicenter phase 2 study of enzalutamide (Xtandi) versus bicalutamide in men with nonmetastatic (M0) or metastatic castration-resistant prostate cancer (M1). These were men who were asymptomatic or mildly symptomatic.

Dr Celestia Higano STRIVE AUA 2015

Dr Higano noted that this was a very late breaking abstract; topline results were only announced a little over a month ago on April 2.

The TERRAIN trial also compared the efficacy of enzalutamide head-to-head against bicalutamide. We’ve updated our EAU 2015 TERRAIN post with the additional data presented here at AUA 2015 in New Orleans.

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As we’re coming to the end of our European Association Urology (EAU) coverage for 2015, I wanted to discuss at a rather more quirky, off-the-wall topic and look at one of the gems from the poster halls at this conference.

This year, it’s the turn of urothelial bladder cancer (UBC), a topic that doesn’t usually get much coverage or respect when it comes to new product development. Part of the challenge is the need for new targets to aim at because the particular patient population doesn’t tolerate high dose chemotherapy very well.

At ASCO last year, perhaps the surprise (and most stunning) data of the meeting was the anti-PDL1 checkpoint data (Genentech’s MPDL3280A) in refractory UBC, a disease where there are a lot of elderly and frail patients who are challenging to treat in many ways. This certainly put more attention on the disease and raised awareness to the potential opportunities for new, targeted and altogether more benign approaches to treatment. Subsequently at ESMO last fall, we also saw early data for an anti-PD1 antibody (Merck’s pembrolizumab) in advanced urothelial cancer.

Checkpoint blockade is not the only potential way to treat UBC though, so what other novel therapeutics are in development in this space?

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EAU 2015 LogoMadrid, Spain – the results of the Medivation/Astellas TERRAIN clinical trial of enzalutamide (Xtandi) versus bicalutamide (Casodex) in men with metastatic castration resistant prostate cancer (mCRPC) were presented today at the European Association of Urology Congress in Madrid (Twitter #EAU15).

Professor Dr. med. Axel Heidenreich. Credit: Universitätsklinikum Aachen

Credit: Universitätsklinikum Aachen

The clinical trial data were presented in a plenary session at EAU15 by Axel Heidenreich (pictured left) who is Professor of Urology & Uro-oncology at the RWTH University and Head of Department & Director of the Urology Program at the University Hospital in Aachen, Germany.

How good are the results, and what impact will they have on the prostate cancer treatment landscape in Europe? Prof Heidenreich kindly spoke with Biotech Strategy Blog (BSB) and shared his thoughts.

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Update May 17, 2015: This post has been updated with the additional TERRAIN trial data presented by Professor Arnauld Villers (Lille) at the 2015 annual meeting of the American Urological Association (AUA) in New Orleans.

Prof Arnauld Villers presents TERRAIN trial data at AUA 2015

Prof Arnauld Villers presents TERRAIN trial data at AUA 2015

Medivation-LogoThere’s nothing better than seeing good news in the early morning email alerts I have set up on cancer research!


astellas-logo-no-sloganToday, it was the turn of Astellas and Medivation to announce the results of the TERRAIN study, which is a primarily European phase 2 trial that began in March 2011 in the prechemotherapy setting for castrate resistant prostate cancer (CRPC). The trial met its primary endpoint of progression free survival (PFS).


Why is this an important landmark in CRPC and what does the initial data show?

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We continue our “pre-game” coverage of the 2014 ESMO Cancer Congress in Madrid with a look at what’s hot (or not) in prostate cancer at ESMO.

The treatment of advanced prostate cancer has been revolutionized in the recent years with the approval of new treatment options such as abiraterone acetate (Zytiga), enzalutamide (Xtandi) and radium-223 dichloride (Xofigo).  We’ve also seen some expensive flops in late stage development such as: dasatinib (Sprycel), TAK-700 (Orteronel), custirsen (OGX-011), lenalidomide (Revlimid) and cabozantinib (Cometriq) – all failed to show a significant overall survival benefit in large phase III trials.  In addition, sipuleucel-T (Provenge) although an approved new treatment, is considered by many to be a commercial failure, which highlights that it’s not just about obtaining regulatory approval as a key success factor.

The results of the accrued phase III trial with ipilimumab (Yervoy) in the pre-chemotherapy setting (recall that the ipilimumab post-docetaxel phase III trial was a failure) is eagerly awaited.

Next up in the pipeline we have next-generation androgen receptor (AR) inhibitors such as ODM-201 (Bayer/Orion) and ARN-509 (JNJ/Aragon). Phase III trials with these new AR inhibitors are recruiting for the treatment of non-metastatic castration-resistant prostate cancer (CRPC).

Other novel compounds of note earlier in development include galeterone for which a phase III trial is planned, and bromodomain inhibitors.

So what’s hot at ESMO 2014 in prostate cancer?

In the second of our preview series we take a critical look at some of the oral presentations in the preliminary ESMO program: what’s a rehash of ASCO 2014, and what new data are worth looking out for when the abstracts are published?

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Yesterday saw the news that Tokai Pharmaceuticals ($TKAI) have filed plans for a $75M IPO, largely based on the potential of their phase 2 prostate cancer compound, galeterone.

My first reaction on seeing this was $75M – that’s a pretty small number.

It’s been many years since I project managed drug development trials but $75M does not go a long way if you want to run a global phase 3 program. It’s certainly pails into insignificance in comparison to the recent $308M raised by Juno in Series A & B financing.

A cynical view would be to see this as the initial investors looking for a ‘save face’ exit strategy. Tokai have spent the last 10 years seeking to bring a novel prostate cancer drug to market, and they are still only in phase 2. To put this in perspective, they were initially ahead of Medivation!

Fast forward 10 years and the prostate market is now highly competitive, with other new products ahead of galeterone in development including next generation androgen receptor antagonists: ARN-509 (acquired by JNJ from Aragon) and ODM-201 (Bayer/Orion). We’ve also seen a several drugs that showed promise in phase 2, fall by the way side in phase 3; dasatinib from BMS and Orteronel  (TAK-700) from Takeda/Millennium readily come to mind.  Caveat emptor!

At ASCO 2014, there was a lot of interesting data in the oral prostate cancer session, which provided insights into the challenges (in addition to the competition) and opportunities that may exist for galeterone.

I have no intention of taking any future position in $TKAI. This piece offers no recommendation on whether you should invest or not.

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One of the most exciting presentations that I heard at ASCO 2014 – the sort that give you goosebumps and elicit a wow from people sitting next to you – was not in the plenary or even a tumour type oral session, but a clinical science symposium.

The subject? Bladder cancer.

The situation? Phase I clinical trial.

The therapy? Anti-PD-L1 therapy with MPDL3280A.

Prof Thomas Powles, Barts Cancer Institute, London

Prof Thomas Powles, Barts Cancer Institute, London

As the presenter, Prof Thomas Powles (Barts), dryly observed to the packed auditorium, it made a welcome change from the ten people who usually show up for bladder cancer sessions! After all, there have been no new approved therapies for this disease for some thirty years.

It wouldn’t have been out of place in the Plenary session, frankly.

By the time the ASCO selection committees cotton on to the fact what many of us know – that immuno-oncology is not only hot, but here to stay and actually changing the way we think about and treat some advanced cancers – some of these new checkpoint inhibitors will already be approved by the FDA.  As one thought leader grumpily said to me:

“It’s not something they understand, nor does it involve the traditional things like breast or prostate cancers, plus it’s all political anyway.”

Ouch. Still, there was a lot to learn from this data, not just in terms of the results in an area of high unmet medical need, but also in our understanding of the immune system and where some future opportunities lie.

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Since 2004, six new prostate cancer treatments have been approved for advanced prostate cancer: docetaxel (Taxotere), sipuleucel-T (Provenge), cabazitaxel (Jevtana), abiraterone (Zytiga), enzalutamide (Xtandi), radium-223 (Xofigo).

In the process, the competitive landscape has been radically transformed.

What we have seen more recently with the PREVAIL and COU-AA-302 data is a move to treat mildly symptomatic men earlier in metastatic disease prior to chemotherapy, thereby delaying disease progression, and in the case of enzalutamide, improving overall survival.

But how early can you go?

The focus of several companies looking to bring new prostate cancer drugs to market is now shifting from symptomatic metastatic castrate resistant prostate cancer (mCRPC) to earlier in the disease setting, i.e. asymptomatic M0 disease.

There are number of critical questions that need addressing, including:

  • Should we treat men with metastatic (M0) castration-resistant prostate cancer (CRPC) who are asymptomatic?
  • Will the treatments be able to demonstrate that taking them means men will live longer and feel better?
  • Will there be a market for AR antagonists such as enzalutamide, ODM-201, and ARN-509 in M0 prostate cancer, where large randomised phase 3 trials are either underway or are planned?
Prof Tombal at ASCO GU 2013

Prof Tombal at ASCO GU 2013

During ASCO GU, I asked one of the leading thought leaders and researchers into this area for his candid perspective.

Subscribers to Premium Content can sign in or sign up in the box below to read what Professor Bertrand Tombal had to say on this topic – his answers may well surprise you.

We’ve been hearing and writing about a substantial amount of news and information on various immuno-oncology developments over the last year, especially in metastatic melanoma and lung cancer, but despite renal cell cancer (RCC) being a proven immune-sensitive disease with known PD-L1 expression, it seems to be the poor cousin to the other two tumour types given the lag in data and relative media attention.

There’s actually quite a lot going on in this disease though, from biomarker work to phase I to III trials that are either ongoing or just started accruing.

We should be hearing much more about the role of anti-PD–1 and PD-L1 antibodies in RCC over the next couple of years, including data from some large randomised controlled trials, but what’s the current state of play?

With that in mind, I was deligted to catch up with David McDermott’s (DFCI) in-depth presentation at ASCO GU in San Francisco over the weekend.  It’s always unfortunate when an interesting talk is left for the final presentation on the last day of a conference, as only a few diehards will be there to catch it!  It was a well thought out discussion though and he covered a lot of interesting ground in this space.

Agents mentioned:
ipilimumab, nivolumab, MK–3475, MPDL3280A, LAG–3, TIM–3, PD-L2, IL–2, sunitinib, everolimus, bevacizumab

Companies mentioned:
BMS, Roche/Genentech, Merck, GSK, Novartis, Pfizer

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