Xtandi, cornerstone of Pfizer's $14B Medivation buy, falls short in closely watched study

Pfizer rolled out the first round of new data since it closed on Xtandi-maker Medivation in September—and the results weren’t good. The blockbuster prostate cancer med fell short in a trial that might have supported longer-term treatment, a potentially lucrative prospect.

With $14 billion socked into its Medivation buy, Pfizer will be under pressure to deliver with Xtandi, which it shares 50-50 with the Japan-based drugmaker Astellas. Along with a late-stage candidate talazoparib, Xtandi was Medivation's chief lure to potential buyers.

Though the new data was just one route to growing the drug, it’s a route that might have led not only to extending treatment duration, but sharpening Xtandi’s edge in the market share battle with Johnson & Johnson’s Zytiga, analysts said.

The 500-patient Plato study was designed to assess Xtandi combined with Johnson & Johnson’s Zytiga against Xtandi alone, in patients whose prostate specific antigen (PSA) levels progressed after Xtandi treatment. Patients in both arms of the study also took the steroid prednisone, and none had been treated with standard chemotherapy.

The idea was that, rather than cycling off of Xtandi when PSA levels progressed, Xtandi patients might add Zytiga to their Xtandi regimens instead. But the Xtandi-plus-Zytiga combo proved no better at keeping cancer at bay than the Xtandi regimen did.

The data follow some less-than-stellar results for Xtandi this year, at least by the lights of some Medivation analysts. The drug brought in $595 million this year, but it’s not ratcheting upward as quickly as market-watchers might hope. After Medivation posted Q2 results, Leerink Partners analyst Geoffrey Porges noted that Zytiga’s marginal market-share losses to Xtandi had declined to 1% per six months, and questioned the company’s full-year sales forecast after flat sequential growth for that period.

“It appears that Xtandi’s growth period may be behind it, or at the very least, that the drug is experiencing a slowdown,” RBC Capital Markets analyst Simos Simeonidis said in a note after first-quarter earnings were released, though he changed that tune somewhat in Q2, saying he continues to expect Xtandi to “become a very successful oncology drug.”

One problem has been that urologists, who treat a significant portion of prostate cancer patients, haven’t been using Xtandi at the levels Medivation wanted. Despite a salesforce overhaul late last year, Porges pointed out that Xtandi had “continued its recent slow upward trajectory” with Q2 results, “clearly limited by slower-than-expected uptake among urologists.”

The Plato study might have offered another leg up with those doctors, Porges said in August. “If positive, this study could point the way to extended durations of Xtandi use in urology, the most valuable market segment.”

That’s not to say that Xtandi can’t make more inroads with urologists. The hope has been that Xtandi would surge on a label expansion, granted in October, based on study data in patients with non-metastatic disease. Earlier this year, the drug beat the chemotherapy Casodex at staving off cancer in patients with, and by a large margin.

Indeed, those study results appear to have helped by the end of Q3, before the FDA nod. As Evercore ISI analyst John Scott noted after Pfizer’s Q3 earnings call, executives said urologists are now writing 26% of Xtandi scripts, up from 20% historically, and urologists tended to up their Xtandi use after learning about that study data.

Xtandi is already a blockbuster, of course, with $1.87 billion in overall sales last year. Earlier this year, it was projected to hit $4.78 billion by 2020, making it one of the world's top drugs by then. Pfizer will add its much-vaunted marketing talents to Astellas' efforts, in a bid to make sure that happens.

by Tracy Staton | Dec 15, 2016

Source: http://www.fiercebiotech.com/