Biotech Strategy Blog

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

Posts tagged ‘ODM-201 Prostate Cancer’

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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Last week saw the release of the majority of the abstracts for the 2013 European Cancer Congress that takes place at the RAI conference center in Amsterdam from September 27 to October 1st (Twitter hashtag #ECC2013). Not yet available are the late-breakers and those abstracts included in the media press conference program.

ECCO Congress BannerThe European Cancer Congress is the euro equivalent of the American Society of Clinical Oncology (ASCO) annual meeting and is organized in alternate years by the European CanCer Organization (ECCO) and European Society for Medical Oncology (ESMO). This year it’s the turn of ECCO who ran an excellent meeting in Stockholm in 2011.

Scan the QR code to download the ECCO Amsterdam Cancer Congress AppHere are links to the #ECC2013 abstracts and searchable Congress programme.

There is also an ECCO App that’s well worth downloading. It offers the meeting program with links to abstracts, as well as floor plans and can also be used to follow the #ECC2013 conversation on Twitter.

ECCO have made it as easy as possible for people to download the app, just scan the QR code and it will take you to the download page for your phone (iPhone or Android).

ECCO have also published their list of abstracts not to be missed – a few on their list that stand out for me include:

Breast Cancer:

1859 – PI3KCA mutations and correlation with pCR in the NeoALTTO trial (BIG 01-06)

Prostate Cancer:

2853: An open-label phase 1/II safety, pharmacokinetic, and proof-of-concept study of ODM-201 in patients with progressive metastatic castration-resistant prostate cancer (CRPC).

2854: The effects of enzalutamide (ENZA) in combination with abiraterone acetate (AA) in patients with bone metastatic castration resistant prostate cancer (mCRPC)

Lung Cancer:

3401:  Updated results of a first-in-human dose finding study of the ALK/EGFR inhibitor AP26113 in patients with advanced malignancies.

3408: Clinical activity, safety and biomarkers of PD-L1 blockade in non-small cell lung cancer (NSCLC): additional analyses from a clinical study of the engineered antibody MPDL3280A (anti-PDL1)

Ovarian Cancer:

In the plenary Presidential sessions several of the presentations focus on ovarian cancer with results being report for the following trials: ICON6 (cediranib), AURELIA (bevacizumab), ICON7 (bevacizumab).

As always I will be mining the posters for gems, and attending as many of the scientific and educational sessions as I can.

Regretably, to offset costs, I will be introducing a paywall for most of the conference coverage from ECC2013 in Amsterdam. In this respect I’m following leading publications such as The New York Times and The Wall Street Journal. I will be providing some additional commentary to those who subscribe to BSB email alerts so do sign up if you have not already done so.

I hope to see you in Amsterdam!

Update Sept 17: Preview of Late Breaking Abstracts and PI3K Abstracts

Sally Church (@MaverickNY) has published her ECCO 2013 preview on Pharma Strategy Blog (free access). Abstracts that caught Sally’s attention included those on T-DM1, everolimus, FLT1 gene varation in NSCLC and evaluation of GDC-0032, a next generation PI3K inhibitor.

Data on GDC-0032 and its early promise in breast cancer was presented at the AACR annual meeting earlier this year.

ESMO 2012 ODM-201 Prostate Cancer PosterAt the 2012 European Society for Medical Oncology (ESMO) meeting in Vienna today, the first published clinical data for a new second generation anti-androgen (ODM-201) was presented. Company representatives inform me that the poster will be available on the Orion Pharma website in a few days. (Update Oct 9: it is now available, but all the text on the PDF of the poster available for download appears to have been intentionally blurred to make it unreadable!)

What makes ODM-201 interesting? The company claimed on their poster, “it is a uniquely designed AR antagonist” yet citing confidentiality reasons refused to answer questions about it or offer a comparison of their drug to other second-generation androgen receptor (AR) antagonists ahead of them in development such as ARN-509, or enzalutamide (Xtandi), which was recently approved in the United States. This perhaps reflects their inexperience as an oncology drug development company, and was a missed PR opportunity.

What the Orion Pharma poster does say is that ODM-201 has “negligble brain penetrance” in nonclinical models. If there are CNS problems with enzalutamide then this would be a major potential advantage, but a more important question in my view is whether ODM-201 has activity against splice variants? The company declined to answer.

Joan Carles, MD PhD (Vall d’Hebron, Barcelona) was the poster discussant and summed up the phase 1 dose escalation trial with 18 patients by summarizing the strengths and weaknesses of the data presented for ODM-201:

Strengths

  • High efficacy
  • Well tolerated
  • Linear pharmacokinetics

Weakness

  • Few patients

We will have to wait for more trial results with ODM-201 and more information on its mechanism of action before it’s potential can be properly evaluated, but at first glance it appears to offer promise.

However, Orion Pharma are seeking to enter a very busy and competitive prostate cancer market. Some of the challenges it faces will be:

  • Which agent to use as a comparator when it moves into randomized trials?  The days of placebo controlled trials in advanced prostate cancer appear to be now over, and most likely it would have to compare itself against enzalutamide if this is the standard of care it will be competing against.
  • Will it need to combine with other agents to be successful? The future is now moving towards combinations. Presuming ODM-201 continues to show promise, will Orion Pharma combine ODM-201 with another novel agent e.g. a PI3K inhibitor? Will they have the courage to do a novel-novel phase 2 combination trial?

The prostate cancer landscape just got even busier with the arrival of ODM-201 on the scene and it will be interesting to watch the drug development strategy of Orion Pharma in partnership with Endo Pharmaceuticals, who have a pain and urology franchise.

I certainly look forward to seeing more data on ODM-201 at future medical meetings and evaluating it against enzalutamide as more data becomes available.

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).

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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