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Posts tagged ‘ARN-509’

Apalutamide is not a winner at ASCO GU

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San Francisco: Today at the 2018 American Society for Clinical Oncology Genitourinary Cancer Symposium, commonly known as ASCO GU (Twitter #GU18), Dr Eric Small (UCSF) will present the results of the SPARTAN phase 3 trial (Link to abstract):

SPARTAN, a phase 3 double-blind, randomized study of apalutamide (APA) versus placebo (PBO) in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC).

Despite the fact this is a positive trial and apalutumide will most likely gain regulatory approval for this indication in the United States, the data presented at ASCO GU is not a winner when viewed in the broader context of the prostate cancer landscape.

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On a day when J&J have just announced that abiraterone (in combination with prednisone) provides a new treatment option for patients with metastatic high-risk castration-sensitive prostate cancer based on the results from the randomised phase 3 LATITUDE study, everyone’s attention is focused on the battle between SPARTAN (apalutamide) and PROSPER (enzalutamide) in M0 disease.

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AACR 2014: Review of novel targeted approaches in lung and prostate cancers

We hope that everyone had a relaxing holiday break and now it’s time to get back to work.  Tomorrow I will review some more of my thoughts in the immuno-oncology space, since that area had a tremendous amount of progress in San Diego with lots of new ideas to process and summarise.

In the meantime, a few people have written in and asked about what was happening with overcoming resistance in various tumour types, was there anything new to say in that space that was in addition to the the detailed previews we covered before the conference?

Actually, there was a quite a few posters and presentations that caught my eye, so I thought this would be a good idea to review them here:

Lung Cancer: HER2, VEGF, T790M, EGFR, erlotinib, gefitinib, trastuzumab, bevacizumab, CO-1686, AZD9291

Prostate Cancer: mTOR, PI3K, Androgen Receptor, enzalutamide, abiraterone, CC214–2, ARN–509, BET Bromodomian inhibition, ODM–201, GDC–0980, GDC-0068, PF–04691502, BKM120, BEZ235

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ASCO GU 2014 Prostate Cancer Preview #GU14

As 2013 comes to an end, rather than look back as many are doing, I’m looking forward to 2014. January is a busy month for cancer meetings with the ASCO organized gastrointestinal cancers symposium (ASCO GI) and genitourinary cancers symposium (ASCO GU) both taking place in San Francisco a few weeks apart.

In fact, looking at the calendar of forthcomings meetings, 2014 looks to have a West Coast focus, with the annual meeting of the American Association for Cancer Research (AACR) taking place in San Diego in April, and the American Society of Hematology (ASH) annual meeting also heading to San Francisco in December.

Transcontinental airfares are notoriously expensive at the last minute so if flying from the East Coast, do make travel plans early!

The ASCO GU symposium takes place at the San Francisco Marriott Marquis from Jan 20 – February 1, 2014. The abstracts for meeting go online at 5pm Eastern Time on Jan 28.

ASCO in a December 19 press release have already announced what will be highlighted on the January 28 press cast, and what many of the media can be anticipated to write about from the meeting.

Perhaps not surprisingly the Medivation PREVAIL trial data (LBA1) is top of the list; the abstract for this presentation has already been published online as Professor Tombal (@BertrandTOMBAL) kindly highlighted on Twitter.

This preview highlights some of the prostate cancer abstracts and presentations to watch out for at the meeting:

Drugs discussed in this post include: enzalutamide (Xtandi), abiraterone (Zytiga), ODM-201, ARN-509, ipilimumab (Yervoy).

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Dr Oliver Sartor shares his thoughts on Prostate Cancer data at ECCO 2013

Amsterdam – Earlier today, I had the great pleasure at the European Cancer Congress to interview Oliver Sartor, MD, the Piltz Professor of Cancer Research in the medicine and urology departments of Tulane School of Medicine in New Orleans, LA.

A recognized expert in prostate cancer, Dr Sartor was gracious enough to give me an impromptu interview in the poster hall at ECCO 2013 and share his thoughts about the prostate cancer clinical data presented in Amsterdam.

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Subscribers should see a SoundCloud below that they can click on to listen to the interview with Dr Sartor. If you don’t see it, send me an email and I will provide a private URL link that will take you direct to SoundCloud.

[soundcloud url=”http://api.soundcloud.com/tracks/113217676%3Fsecret_token%3Ds-Ka2sf” params=”” width=” 100%” height=”166″ iframe=”true” /]

ASCO GU 2013 Prostate Cancer Preview #GU13

What’s hot in prostate cancer at the forthcoming American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) (twitter hashtag #GU13) that takes place in Orlando from February 14 -16?

That’s the question I was asked recently, and while the abstracts have not yet been published, (embargo lifts at 6pm ET on February 12, 2013) the titles of the posters and choice of oral presentations offer some insight into what may be newsworthy data.

In the oral abstract session on February 14, 2012 two of the presentations of particular interest to me are:

Bristol Myers Squibb dasatinib (Sprycel) Phase 3 Trial Data

Abstract #LBA8. Overall survival (OS) and safety of dasatinib/docetaxel versus docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC): Results from the randomized phase III READY trial.

Presenter: John C. Araujo, MD, PhD

I correctly predicted in my October 2012 blog post that the dasatinib phase III prostate cancer trial data would be at ASCO GU.

Bristol Myers ($BMY) stock has experienced an upwards run in the last few weeks, so we will soon see whether the company has a new treatment option for prostate cancer and one with a very different target (Src).

I have no thoughts on whether the data will be positive or negative. I hate to sit on the fence, but the impression I have is the results could go either way.

Aragon Pharmaceuticals ARN-509 

Abstract #7. ARN-509 in men with high-risk nonmetastatic castration-resistant prostate cancer (CRPC).

Presenter: Matthew R. Smith, MD, PhD

I recently wrote about the ongoing Medivation v UCLA/Aragon litigation on this blog. ARN-509 is a second-generation androgen (AR) inhibitor that along with enzalutamide came out of the work by Charles Sawyers and Michael Jung’s lab at the University of California Los Angeles (UCLA).

Irrespective of whether Medivation appeals the recent summary judgement decision in favor of Aragon, ARN-509 is of considerable interest. Sawyers observed in the preclinical testing that it may be a more complete AR antagonist than enzalutamide; see Sally Church’s Interview with Dr Charles Sawyers on Pharma Strategy Blog for further commentary.

At ASCO GU there is also an oral presentation on the pre-chemo data for abiraterone (Zytiga) from the COU-AA-302 trial that I wrote about from ASCO last year.

Without much fanfare, and without any significant overall survival data, abiraterone’s pre-chemo indication was approved by the FDA last December.  It will be interesting to see what new data is presented at the meeting.

There are also several interesting posters that did not make into the short oral session.  One to look out for is the first data for enzalutamide (Xtandi) in hormone-naive prostate cancer:

Abstract #18. Enzalutamide monotherapy: Phase II study results in patients with hormone-naive prostate cancer.

Presenter: Bertrand Tombal, MD, PhD (@BertrandTOMBAL)

It will be interesting to see how enzalutamide compares to bicalutamide, in what is a market segment with a very large potential.

Another poster of note is the pain analysis for radium-223 (Alpharadin) (Abstract#19).

I’m also looking forward to the poster on the use of chimeric antigen receptor (CAR) modified T cells to target prostate-specific membrane antigen (PSMA) (Abstract #72).  This is an emerging technology that was highlighted at ASH 2012.

For those interested in learning more about the potential of CAR based therapies, Sally Church, PhD (@MaverickNY) will be publishing a report in the not too distant future.

ASCO GU 2013 (#GU13) looks to have some interesting data in prostate cancer and I look forward to contributing to Xconomy from the meeting.

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Update Feb 12, 2013 – Dasatinib phase 3 prostate trial is a failure

Well, it’s gone 6pm and the #GU13 abstracts are now accessible on the ASCO GU Symposium website. The big news is that the dasatinib phase 3 trial data is negative!

According to the abstract, “The addition of DAS to standard-of-care chemotherapy in mCRPC pts did not improve OS.”

As commentators have already noted on Twitter, this is disappointing given the promise of the phase 1/2 trial results that were published in the journal “Cancer” on January 1, 2012 by Dr Araujo and colleagues.

Update Feb 15, 2013 – Winners & Losers at ASCO GU

Thanks to @ldtimmerman for editing my guest post on Xconomy. Here’s a link to my post about the prostate cancer drug winners and losers at ASCO GU 2013.

ESMO 2012: ODM-201 a new generation antiandrogen for advanced prostate cancer

One of the late-breaking abstracts (not yet published) that I am looking forward to at the forthcoming annual Congress of the European Society for Medical Oncology (ESMO 2012) in Vienna is on ODM-201 (Orion Pharma):

LBA25-PR:  ARADES trial: A first-in-man, open-label, phase I/II safety, pharmacokinetic, and proof-of-concept study of ODM-201 in patients (pts) with progressive metastatic castration-resistant prostate cancer (mCRPC)

ODM-201 is a new antiandrogen from Finnish company, Orion Pharma, and is being developed in partnership with Endo Pharmaceuticals (NASDAQ: ENDP).

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Orion Pharma LogoIn a corporate presentation, Orion Pharma describe ODM-201 as:

  • Potentially best-in-class antiandrogen
  • Does not enter brain in preclinical models
  • No testosterone increase in animal models
  • Well tolerated

“We are studying and developing an anti-androgen with qualities that currently cannot be found in any of our or our competitors’ drugs”

says Mika Mustonen (@MikaMustonen), Head of Oncology, Research and Development at Orion in an article, “Pursuing a targeted drug for prostate cancer” published by the company. Mustonen says:

“The research on our new drug candidate, ODM-201, suggests that we may be able to provide patients with a new alternative for the treatment of prostate cancer.”

Of note, is Orion’s focus on biomarkers, which may help predict which patients are more likely to respond to the therapy. According to Mustonen:

“Biomarkers increase the chance of success.  By following them we can study topics that have not been considered before in this type of research.  We can predict different phases of the disease, survey any safety risks associated with the drug and find out what kind of patients benefit most from the drug.”

At ESMO 2012 (Twitter hashtag #ESMO12) I expect we will hear preliminary data from the ARADES 3104001 phase 1 dose escalation study (NCT01317641) with ODM-201.

According to clinicaltrials.gov this multicenter, non-randomized clinical trial is being undertaken at sites in Finland, Czech Republic, France, United Kingdom and the United States.

After 12 weeks in the phase 1 dose escalation study, patients with stable disease can continue treatment in a phase 2 extension study on the safety and tolerability of ODM-201 (NCT01429064).

As of May 2012, Orion Pharma reported that the ARADES 3104001 phase II expansion component had 105 patients enrolled, with 3 dose levels to be expanded.

Company senior management have told me they “are very excited about the ODM-201 data,” to be presented at ESMO. I have not seen the data, but presume the results will be positive. After all, company executives don’t get excited about negative data!

Is there a market for a new antiandrogen?

Although Medivation are first to market with their androgen receptor (AR) inhibitor, enzalutamide/MDV3100 (Xtandi) that does not mean that other companies will not be able to make in-roads into the market with cheaper or more effective AR antagonists.

In a Pharma Strategy Blog interview with Sally Church, Dr Charles Sawyers noted that Aragon’s ARN-509 (another AR inhibitor in development) is “more potent” than enzalutamide and “might produce a higher percentage of responders or longer duration of response.”

Medivation recently announced that enzalatumide is available in the United States for patients with metastatic castration resistant prostate cancer previously treated with docetaxel.

At a price of $7,450 a month, however, Xtandi is considerably higher than Johnson & Johnson’s Zytiga.  This aggressive premium pricing strategy opens the door to competitors who may offer equally effective, but less expensive drugs.

The prostate cancer market remains a dynamic one and very much one to watch over the next few years.

I look forward to learning more about ODM-201 at ESMO 2012.

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MDV3100 shows survival in Advanced Prostate Cancer

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.

Prostate Cancer Market to expand from $1B to $5B by 2015

Launch of Zytiga (abiraterone acetate) at 2011 annual meeting of American Urological Association (AUA) in Washington DCThe market for prostate cancer therapies is set to expand from $1 billion currently to $5 billion by 2015, according to analysts reported by this morning’s Washington Post/Bloomberg news.  This is perhaps no surprise given the recent approval of abiraterone acetate (Zytiga®) from Ortho Biotech (JNJ).

New clinical data on prostate cancer clinical trial results is expected at the 2011 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago this weekend from many of the prostate cancer therapies in development such as MDV3100, TAK700, ARN-509, cabozantinib (XL184), ipilimumab, custirsen (OGX-11), BPX-101, alpharadin, denosumab (Xgeva®) and Prostvac-VF.

Indeed, one could argue that prostate cancer is becoming a competitive marketplace.  Any emerging biotechnology company that is not already developing a prostate cancer drug is likely to find it a hard market in which to create a blockbuster.  By the time any drug comes to market, there will be incumbents with effective products who have captured market share.

Prostate cancer is an exciting market to watch from a marketing strategy and patient perspective, as several companies potentially bring new products to market over the next few years.

However, the bottom line is that patients will live longer as a result of all the innovation that is taking place.  Not only that but physician education and awareness of how to treat this disease is also likely to improve as they seek out knowledge on new therapies and treatments.  This to many will make a major difference.  At the recent American Urological Association (AUA) annual meeting, the sessions on treatment of prostate cancer were standing room only.  There is clearly a demand for knowledge out there as the treatment paradigms change.

At the other end of the spectrum, there is also innovation taking place in terms of improved diagnosis and treatment of prostate cancer.  Whether we should screen all men for PSA remains a controversial topic, although use of risk calculators do appear to offer less false positives.  Indeed, calculating risk is going to be one of the key areas that primary care physicians and urologists need to focus on, particularly in the light of the PIVOT trial data that was presented at AUA, showing radical prostatectomy (with risks including incontinence and erectile dysfunction) was not better than watchful waiting in low-risk, early stage disease.

However, a presentation I am looking forward to at ASCO 2011 is on circulating tumor cells (CTC) and whether these can be a prognostic or even a predictive biomarker.   Both the phase III MDV3100 and abiraterone acetate clinical trials captured CTC data.  It will be exciting news at ASCO 2011 if circulating tumor cells that require only a blood sample offer an improvement over PSA not only for detection of prostate cancer, but in monitoring the disease over time.

I will be at ASCO 2011 this weekend, and look forward to writing more on prostate cancer from the conference!

American Urological Association Annual Meeting 2011 Satellite Symposia

By on May 12, 2011

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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