Anyone thinking that the prostate cancer market would see some calm after the storm whipped up by the recent launch of Medivation’s Xtandi had better watch out. Next week’s Asco Genitourinary Cancers Symposium has given standout roles to several projects that have so far barely made a ripple in this setting.
Although the embargo on the abstracts from Asco-GU will not be lifted for another week, the meeting programme has already revealed the prominent billing given to two drugs – Bristol-Myers Squibb’s Sprycel and Aragon Pharmaceuticals’ ARN-509. With Takeda’s orteronel nearing the end of phase III and Johnson & Johnson hoping that Zytiga will make some noise in pre-chemo use there is still plenty to play for.
Under the radar
Sprycel’s possible use in prostate cancer has not been strongly touted by Bristol despite the large Ready trial nearing data readout. The Src-family kinase inhibitor is marketed for chronic lymphocytic leukaemia and acute lymphoblastic leukaemia.
Bristol’s reticence might hint that a positive outcome is unlikely; nevertheless, the study’s result will feature at an oral session at Asco-GU. In the 1,500-patient trial Sprycel is being added on top of docetaxel chemotherapy with a prednisone backbone, and the primary endpoint is improvement in overall survival.
Src kinase represents a potential new target in prostate cancer treatment, though other agents with this mechanism have not fared well. A smaller study of Sprycel in this setting indicated declines in PSA and bone markers, with a favourable toxicity profile.
Aragon’s ARN-509 is another project about to hit the limelight at an oral presentation at Asco-GU. This agent is an anti-androgen that has so far only yielded preclinical data, and as such the results of its phase I/II study will be keenly watched. Aragon itself is a private company that only recently came to prominence after closing an impressive $42m venture capital round (Celladon, Aragon top table for biggest VC rounds of Q1, May 10, 2012).
Yet ARN-509 could be of huge interest, sharing the same scientific inventor as Medivation’s Xtandi. Indeed, the two companies have locked horns in court over rights to ARN-509, and in December the Superior Court of California ruled in favour of Aragon – a decision against which Medivation will almost certainly appeal.
Aragon’s private backers must surely see a takeover by Medivation as one solution to the dispute, and an impressive performance by ARN-509 could presage just such an outcome.
Medivation of course is the new kid on the prostate cancer block, the survival benefit of its Xtandi having impressed hugely. And barely months after US launch Xtandi is making its presence felt.
In the fourth quarter of 2012, the first full quarter in which Xtandi was on the market, US sales of its rival Zytiga totalled just $114m – a quarter-on-quarter fall of 16%. While one quarter might in itself not count for much, it does highlight the battle ahead.
Zytiga has counterattacked with an additional approval in the lucrative pre-chemo setting, which some analysts estimate might be more than twice the size of post-chemo, and as such its first-quarter sales performance will be closely watched (Zytiga needs to sprint through window of opportunity, December 11, 2012).
Pre-chemo Zytiga was approved on the strength of a 1,088-patient trial from which next week’s Asco-GU will see an updated analysis. Xtandi itself is in Prevail, a study in 1,680 chemo-naive patients due to end next year – though the big unknown is the extent to which it might already be used off-label in this setting.
A phase III project being tested separately in pre and post-chemo prostate cancer patients is Takeda’s hormone therapy orteronel, although there is no indication yet whether any data from these might be presented at the meeting.
Orteronel is another prostate cancer agent that has largely sailed under the radar, and analysts forecast launch in 2014 and consensus 2018 sales of a modest $571m. Like the dark horses that have already secured key spots at Asco-GU, it might not remain in the shadows for long.
|Possible prostate cancer data at Asco-GU|
|Sprycel||1,500 pts, docetaxel combo (Ready)||OS and safety data||NCT00744497|
|Zytiga||1,088 pts, chemo-naive setting||Updated interim analysis||NCT00887198|
|orteronel||1,454 chemo-naive, prednisone combo||Completion imminent||NCT01193244|
|orteronel||1,083 post-chemo, prednisone combo||Completion imminent||NCT01193257|
|ARN-509||Phase I/II, 123 pts||Proof-of-concept data||NCT01171898|