Early halt augurs well for Xtandi expansion

The worst that could be said about the findings from Medivation’s Prevail trial of prostate cancer drug Xtandi is that it may struggle to show unambiguous overall survival results in the final analysis. The decision by the data monitoring board to halt the trial in pre-chemotherapy patients early and allow crossover of patients in the placebo arm, though, is incredibly good news for the prospects of a label expansion, not to mention patients hoping for new treatment options.

The data should allow Medivation and partner Astellas to persuade regulators to add first-line treatment to its label, which now cites only patients who previously have been treated with docetaxel. While a good share of Xtandi sales are already believed to be in this first-line setting, a label expansion would allow sales representatives to begin marketing to the urologists who usually treat the pre-chemo population – and give it better leverage against Johnson & Johnson’s Zytiga.

Unlocking the data

Following a pre-specified interim analysis triggered by the 516th death in the 1,717-patient trial, the independent data monitoring committee calculated that Xtandi had significantly improved both overall and radiographic progression free survival (PFS) when compared to placebo. Importantly, the drug reduced the risk of progression by 81%.

The overall survival calculation of 30% reduction in death was, like the PFS finding, highly significant at p<0.0001. Those numbers prompted an immediate cessation of the placebo-controlled part of the trial, with all patients randomised to the placebo arm offered Xtandi.

The improvement in median overall survival to 32.4 months from 30.2 months looks a little less impressive, although Medivation executives took great pains to explain that it is an interim calculation and that drawing conclusions from that figure is premature. Of the Xtandi patients, 72% were still alive when the committee analysed the data, as were 65% of placebo patients. “If half of our patients had died we could be able to tell you the median,” chief executive David Hung told analysts in a conference call.

Shares rose 8% to $53.89 yesterday following announcement of the trial’s halt, and were up another 6% to $56.93 in early trading today.

Catching up

Xtandi is behind Zytiga in achieving pre-chemo consent from the FDA and other global regulators, pending the results of Prevail. The FDA approved Zytiga in this setting last December. It seems probable that the agency would wave through Xtandi sometime in mid-2014, although the data will probably encourage specialists to use it well before that date.

Despite the preliminary nature of the overall survival from Prevail, Xtandi was able to show statistical significance – something J&J was unable to do in its smaller COU-AA-302 trial of Zytiga (Strong competitor data reveals the real threat to Provenge, March 9, 2012). This should give the Medivation agent another point of differentiation over Zytiga in addition to the latter’s need to be used with prednisone.

While a true median survival calculation could not be made, the company asserted that the FDA’s reviewers will look primarily at the hazard ratio, which will also be data that “resonate well with urologists,” chief commercial officer Cheryl Cohen said.

Xtandi has met investors’ highest hopes at nearly every test and has proven itself a worthy adversary to Zytiga. J&J needs to make the most of its incumbent, as between competition from Medivation and Astellas and patent expiry in 2017, Zytiga revenues are projected to begin shrinking in just two years.

Trial ID
Prevail NCT01212991

To contact the writer of this story email Jonathan Gardner in London at jonathang@epvantage.com or follow @JonEPVantage on Twitter

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