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Posts from the ‘Prostate Cancer’ category

Did Galeterone ARMOR2 Prostate Cancer Data Impress at ESMO 2014?

At the 2014 ESMO Congress in Madrid, Mary-Ellen Taplin, MD (Dana-Farber Cancer Institute, Boston) presented the results of the Tokai Pharmaceuticals (NASDAQ $TKAI) ARMOR2 clinical trial of galeterone in men with advanced prostate cancer.

ESMO 2014 Dr Taplin Galeterone ARMOR2 Presentation

Galeterone has a novel triple mechanism of action. In effect, it is a CYP17 lyase inhibitor (like abiraterone) that has additional anti-prostate cancer actions including androgen receptor (AR) inhibition (like enzalutamide). It also causes AR degradation that decreases AR levels.

Tokai’s IPO last month is reported by Renaissance Capital to have raised $98M for the company, with most of the funds going to prior investors including Novartis Bioventures which owned 28 percent.

Shares in $TKAI were initially priced at $15. They soared to a high of $30 thanks to high insider buying and a high trading volume. Novartis Bioventures were reported by Renaissance to have bought $20M.

As of publishing this post, the stock is now trading at $15.40, slightly above it’s IPO price. So have Novartis and others made a good investment?

Tokai Pharmaceuticals Stock Info Oct 3, 2014The market cap of $TKAI, according to their Investor Relations page (screenshot pre-market Oct 3, 2014 shown above) is $336M – not high for a company about to enter phase III drug development.

Readers are no doubt aware of the Feuerstein-Ratain rule that predicts a phase III cancer trial will be a failure when undertaken by a company with a market cap less than $300M. As Adam noted in his May 6 story on The Street earlier this year, “For companies with market caps between $300 million and $1 billion, the oncology phase III success rate is 59%.”

The big questions now are did the data for galeterone from the ARMOR2 trial impress at ESMO 2014 in Madrid and what are the challenges and opportunities in the planned phase III ARMOR3-SV trial? 

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DISCLAIMER: Please note this piece offers no stock advice, is not a solicitation to invest in $TKAI and makes no recommendation on whether to buy or sell. It merely offers commentary and analysis of the data presented at ESMO 2014. Readers should do their own due diligence prior to making any investment decision.

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What’s hot in prostate cancer at ESMO 2014? #ESMO14

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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Update on potential of Galeterone in Prostate Cancer $TKAI

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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A potential new target for prostate cancer drug development

A predictive biomarker for prostate cancer drug resistance may lead to new drug development opportunities.

At ASCO 2014, one of the prostate cancer highlights was the oral presentation by Emmanuel Antonarakis MB BCh, Assistant Professor of Oncology at Johns Hopkins.

He presented elegant research, albeit in a small group of patients, about how constitutively active splice variants (AR-V’s) may represent one potential mechanism of resistance to androgen receptor (AR) signalling inhibitors such as enzalutamide (Astellas/Medivation) and androgen synthesis inhibitors such as abiraterone (JNJ).

I spoke to Dr Charles Ryan, Professor of Medicine and Urology at the University of California San Francisco (UCSF) about the significance of the data to clinical practice, and the new drug development opportunities that may follow-on from it.

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Insights on the enzalutamide PREVAIL data pre-chemotherapy in advanced prostate cancer

At the ASCO GU meeting in January, Dr Thomas Beer presented the initial data for the PREVAIL trial, which explored enzalutamide (Xtandi) in castrate resistant prostate cancer (CRPC) prior to chemotherapy. Reactions to the data were mixed with many analysts, perhaps naively, focusing on the significant temporal survival benefit (2 months) rather than the 29% hazard ratio, which demonstrates the magnitude in the reduction in the risk of death over the control arm.

This weekend at the American Urological Association (AUA) meeting in Orlando, Dr Christopher Evans (UC Davis), presented the updated data, including the survival curves and a subset analysis for visceral and non-visceral disease. He focused on the clinical benefits that were clinically meaningful to the urology audience.

I have to say that the data shown was both compelling and impressive to me.

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AUA 2014 – New targets in prostate cancer

Over the last few years we have seen new therapies emerge for the treatment of advanced prostate cancer from immunotherapy to chemotherapy and second generation hormone therapies. Each of these has increased survival and outcomes. Along the way though, a host of other agents have fallen by the wayside with a raft of negative phase III trials that did not live up to their phase II promise. These include atrensentan, dasatinib, ipilimumab, lenalidomide and more recently, custirsen.

Much of the focus has, however, been on the hormonal drugs, abiraterone (Zytiga) and enzalutamide (Xtandi) in both the pre and post chemotherapy settings. One thing has become clear though – over time the responses attentuate as resistance sets in. This is very common with oral therapies.

Some big questions to consider here are:

  • What causes it?
  • How can we overcome adaptive resistance?
  • Would combination approaches produce synergistic results?
  • Or should we consider new targets with a different mechanism of action (MOA)?

The answers to these questions are now being eagerly explored through basic, translational and clinical research. I was very impressed with the quality of research and breadth of fresh ideas and approaches emerging from the SBUR, SUO and UOR sessions at AUA this year, including new combination trials already in the planning phase.

In the past, Bertrand Tombal (Belgium) talked about the Grand Cru year for clinical research in CRPC. In the future we may well look back at 2014 as a similar Grand Cru year for basic research for prostate cancer, if the findings translate to clinic. The bench-to-bedside process is very much alive and well in urologic research.

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ASCO GU 2014: Will there be a market for Medivation’s enzalutamide in M0 prostate cancer?

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.

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ASCO GU 2014: Will Galeterone make it to market in Prostate Cancer?

San Francisco – Tokai Pharmaceuticals is a case study in how not to do drug development.

A company, founded in 2004, with a novel prostate cancer drug has taken 10 years to make it to phase II drug development while competitors such as Medivation and Johnson & Johnson have brought similar new drugs to market in multiple prostate cancer indications.

armor-logoAt ASCO GU this week (Abstract 71), Tokai reported part 1 of their phase 2 ARMOR2 trial with reformulated galeterone (TOK-001) in men with prostate cancer at various stages of the disease in a poster.  Part 2 of the study will enrol 136 patients with a once daily dose of 2550 mg.

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ASCO GU Interview with Dr Tom Beer on Medivation PREVAIL trial data

This week we turn our focus to the American Society of Clinical Oncology Genitourinary (ASCO GU) symposium being held in San Francisco.

The hottest topic is highly likely to be the Medivation and Astellas data for enzalutamide (Xtandi) in the pre-chemotherapy setting in men with advanced prostate cancer who are asymptomatic or slightly symptomatic and naive to chemotherapy.  Previously, I wrote in detail about the Medivation announcement regarding the interim analysis where the PREVAIL trial was found to meet its primary endpoint (open access).

Dr Tom Beer, OHSU

Dr Tom Beer, OHSU

The company subsequently stated that the data had been accepted as a late breaker for the the ASCO Genitourinary meeting in San Francisco this weekend.  That data is being presented on Thursday morning in the oral prostate cancer session by Dr Tomasz Beer (OHSU), who is the Deputy Director of the Knight Cancer Institute and a prostate cancer specialist.

The ASCO GU 2014 abstracts will be available for perusing as of 5pm ET today.

This week I caught up with Dr Beer to discuss not only the details relating to the PREVAIL data, but also how enzalutamide (Xtandi) potentially fits in the advanced prostate cancer competitive landscape given that he also participated in the abiraterone (Zytiga) COU-AA-302 trial in the same clinical setting.

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ASCO GU 2014: Why does the Medivation PREVAIL trial matter?

This week sees the start of the American Society of Clinical Oncology Symposium on Genitourinary Cancers (ASCO GU) in San Francisco.

Prostate cancer has certainly been in the minds of investors the past few weeks in anticipation of the COMET-1 prostate cancer trial results for cabozantinib (Cometriq).

The share price went on a run-up until Exelixis CEO Michael Morrissey took yet another trip to the biotech ATM machine.  Somehow, this doesn’t come as any surprise given past performance.  The key issue at stake here, however, is will the COMET-1 trial be positive or negative?  The outcome is much anticipated and will no doubt influence the chances of successful approval for cabozantinib in advanced prostate cancer.  Data is expected sometime in first half of this year.

What we can expect in the media this week is more news on the Medivation and Astellas phase 3 trial PREVAIL clinical trial of enzalutamide (Xtandi) in men with advanced prostate cancer who had not yet received chemotherapy.  The ASCO GU abstracts are publicly available at 5pm on Tuesday.

Currently, the key data from oncology medical conferences is focused squarely on Medivation’s enzalutamide and the PREVAIL data.  It seems a good idea to discuss what are the key things to watch out for?

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