Medivation Inc. and Astellas Pharma Inc.are counting on the strength of the Phase III trial results for their andogren receptor signaling inhibitor enzalutamide to gain priority review from FDA for their newly submitted NDA, despite the presence of other breakthrough prostate cancer therapies like Zytiga (abiraterone) and Jevtana (cabazitaxel) on the market.

Enzalutamide, formerly known as MDV3100, has generated a lot of buzz since the Phase III trial was stopped early because of positive results in castration-resistant prostate cancer patients, and analysts expect it to get quick treatment from regulators.

The companies announced the NDA submission May 22 and expect to hear within 60 days if the application has been accepted for review by FDA. If the request for a six-month priority review is granted, the drug would hit the market before the end of the year, if approved.

“We expect enzalutamide to launch at year-end, and we estimate first full-year sales of $368 million globally, of which, Medivation would receive an estimated $130 million U.S. sales split, plus an estimated $21 million ex-U.S. royalties,” Wedbush analyst David Nierengarten wrote in a May 22 note.

Medivation’s drug is one of many new contenders in the prostate cancer space. The market for hormone-refractory prostate cancer therapies is now booming, with multiple treatments approved in the last few years, all with proven survival benefits Also see "Prostate Cancer Market Snapshot: More Than Provenge" - Pink Sheet, 22 November, 2010.. Johnson & Johnson’s Zytiga was approved in April 2011 for post-chemo use and has had a strong launch, including off-label penetration into chemo-naïve patients Also see "J&J’s Zytiga –The Anatomy Of A Cancer Launch" - In Vivo, 30 November, 2011.. Sanofi’s Jevtana was cleared by FDA in June 2010 for use after chemotherapy as well, but while it showed a 2.4 month improvement in OS, the drug also has been associated with significant side effects.

Nierengarten expects an enzalutamide approval would undercut Zytiga’s performance. “By comparison, Zytiga’s recent sales totaled $200 million globally for the first quarter 2012. We believe that enzalutamide’s efficacy and prednisone-free dosing present a compelling case for urologists/oncologists and expect it to take market share from Zytiga,” he said.

AFFIRM Could Launch Commercial Success, PREVAIL Could Assure It

Enzalutamide has been studied in prostate cancer patients whose disease returns or persists after being treated with the chemotherapy docetaxel. Interim data from the AFFIRM trial, presented at Genitourinary Cancers Symposium in February, showed that patients given the investigational drug in the 1,200-person study lived 4.8 months longer than their counterparts on placebo, corresponding to a 37% reduced risk of death Also see "Phase III Data AFFIRM Safety As Well As Survival For MDV3100" - Pink Sheet, 1 February, 2012.. Additional analyses revealed that men treated with the drug were significantly more likely to have a soft tissue response and at least a 50% reduction of their prostate-specific antigen (PSA) levels. There was also no increase in the rate of higher-grade adverse events; seizures (a potential concern from earlier research) occurred at low frequency.

The drug is also being tested in patients who have not yet received docetaxel. Medivation is enrolling patients in a Phase III trial called PREVAIL in earlier-stage prostate cancer patients who are chemo-naïve. PREVAIL will enroll 1,700 patients and look at progression-free survival and overall survival as co-primary endpoints. In contrast, J&J’s Phase III for Zytiga in the same population has enrolled only about 1,000 patients, putting the robustness of its dataset at a disadvantage with respect to payers, assuming that both companies file on the OS endpoint. Data from the Zytiga trial will be presented as a late-breaking abstract at the American Society of Clinical Oncology meeting in June.

“Depending on the results of Zytiga's ‘302 trial in the pre-chemo setting to be reported at ASCO, Medivation may be in a position to revise the plan for interim analysis for PREVAIL and have data readout as early as this year in the best case scenario,” Leerink Swann analyst Howard Liang said in a May 9 note.

Medivation will also be making presentations about enzalutamide at ASCO, although not the PREVAIL results. Further quality of life data from AFFIRM will be presented that shows enzalutamide improves quality of life by 43.3% compared to a placebo response of 17.8%.Phase II data will be released from the TERRAIN trial comparing bicalutamide with enzalutamide in advanced prostate cancer patients who have progressed on androgen therapy or following surgical castration; and from a study of enzalutamide alone or in combination with dutasteride and leuprolide as neoadjuvant therapy in men with intermediate and high-risk prostate cancer undergoing prostatectomy.

Astellas and Medivation announced a worldwide co-development and co-commercialization deal for MDV3100 in October 2010, which at the time was in one Phase III trial for metastatic castration-resistant prostate cancer in post-chemo patients. Medivation got $110 million in upfront cash, pre-launch milestones totaling $335 million and post-launch milestones totaling $320 million. Astellas is responsible for two-thirds of development costs in the U.S. and Europe. Medivation will retain 50% of profits in the U.S. and will realize tiered, double-digit royalties in ex-U.S. territories. The company has exercised its right to co-promote the drug in the U.S., providing 50% of the sales force and medical support resources.

Medivation is currently in a legal dispute with the University of California Los Angeles over two compounds that are similar to enzalutamide; the San Francisco-based company claims in a breach of contract suit that UCLA researchers kept secret and developed those compounds using the same screening technology. The Regents of the University of California licensed these compounds – A51 and A52 (renamed ARN-509) – to a company the UCLA researchers founded, Aragon Pharmaceuticals Inc. Medivation contends that it holds rights to all related molecules developed under a licensing agreement and a research agreement with the UC Regents, the governing board of the university Also see "Medivation Battles UCLA Over Rights To Prostate Cancer Compound" - Pink Sheet, 21 May, 2012..

More Competition In Prostate Cancer? Medivation’s Enzalutamide Now With FDA

More from Clinical Trials

More from R&D