There’s nothing better than seeing good news in the early morning email alerts I have set up on cancer research!
Today, 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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At 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:
- High efficacy
- Well tolerated
- Linear pharmacokinetics
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.