Assistant Managing Editor
When Medivation Inc. gained clearance in March to start its Phase III trial of MDV3100 in prostate cancer, a company executive told BioWorld Today the firm would consider partnering the drug if the right opportunity came along - as it had for Alzheimer's disease drug Dimebon, which scored a potential $725 million deal with Pfizer Inc. last year.
For MDV3100, the right deal came along this week.
Astellas Pharma Inc. agreed to pay South San Francisco-based Medivation $110 million up front for rights to the androgen receptor antagonist, with up to another $655 million in potential milestones - $335 million precommercial and $320 million postcommercial - as well as 50 percent of U.S. profits and tiered double-digit royalties on ex-U.S. sales.
On top of that, Astellas takes over two-thirds of the development costs, including funding two-thirds of the ongoing Phase III AFFIRM study, which last month began enrolling patients with castration-resistant prostate cancer who previously were treated with docetaxel, said David Hung, Medivation's president and CEO.
Not that Medivation needed a partner to move MDV3100 into Phase III. The firm, which had $237.7 million in cash as of June 30, was prepared to launch AFFIRM on its own. But investors clearly had been waiting for a collaboration, and the addition of big pharma muscle means expanding MDV3100 more quickly into broader prostate cancer indications.
The first Phase III is testing the drug in patients following chemotherapy failures.
"As large a market as that is, it's still not the biggest," Hung told BioWorld Today. "You have to go after the upstream indications," hitting first-line and second-line patient populations.
"We mapped out a development program to hit those upstream indications," he said, adding that additional trials are expected to follow AFFIRM, though Medivation and Astellas have not yet "talked in great detail about what those will be."
Since the progression of prostate cancer is driven by the testosterone androgen, MDV3100 is designed to work by blocking the binding of testosterone to the androgen receptor, thereby preventing the androgen receptor from invading the cell's nucleus and promoting further growth.
Prostate cancer is estimated to affect about 1 million men in the U.S.
The castration-resistant form, also known as hormone-refractory prostate cancer, has few treatment options and a median survival of about 12 months.
Hung acknowledged a "healthy interest" among prospective partners for MDV3100, particularly given that the prostate cancer space has been hopping with news this year.
In April, Seattle-based Dendreon Corp. impressed investors with data from its confirmatory Phase III trial showing that cancer vaccine Provenge (sipuleucel-T) improved overall survival in men with metastatic androgen-independent prostate cancer, and a month later Los Angeles-based Cougar Biotechnology Inc., which is in two Phase III trials with abiraterone acetate in previously treated and chemotherapy-naïve patients, was snatched up by Johnson & Johnson in a deal worth nearly $1 billion. (See BioWorld Today, April 15, 2009, and May 26, 2009.)
And prostate cancer led the charge at this year's American Society of Clinical Oncology meeting, with Bothell, Wash.-based OncoGenex Pharmaceuticals Inc. reporting stellar Phase II survival data with its clusterin-inhibiting antisense drug, OGX-011, in combination with docetaxel in patients with advanced disease. (See BioWorld Today, June 2, 2009.)
"It's such a large opportunity," Hung said, so when Medivation looked at potential partners, "we looked at the overall total value of the deal."
Besides the hefty up-front and milestones - "and there aren't too many [deals] of this size in oncology for a drug targeting a single cancer," Hung said - a partnership with Astellas also gives Medivation access to the Tokyo-based pharma's sales force in urology, "the gatekeepers for prostate cancer treatment."
Astellas already markets benign prostatic hyperplasia drug Flomax (tamsulosin) and overactive bladder product Vesicare (solefinacin succinate), "so that will give us great entry into the urology market," Hung added.
Rodman & Renshaw analyst Elemer Piros estimated in a research note that U.S. sales of MDV3100 could hit $700 million seven years after launch, with peak potential of $1.2 billion in 2025.
But some skeptics remain, as well. Analyst Jonathan Aschoff, of Brean Murray Carret & Co., wrote that he was "not encouraged" by the outcome of the ongoing AFFIRM trial, nor the ongoing CONNECTION trial, which is testing the firm's other late-stage product, Dimebon, in patients with mild to moderate Alzheimer's.
But like MDV3100, Dimebon (latrepirdine) had produced strong enough data to nab a lucrative pharma deal. Last year, New York-based Pfizer paid a whopping $225 million up front, with up to another $500 million in potential precommercial milestones. Under that deal, the firms agreed to share U.S. development and commercialization costs and profits on a 60/40 basis, with Pfizer holding the larger share. (See BioWorld Today, Sept. 4, 2008.)
Dimebon also is being tested in a 12-month Phase III trial, with results due in the first half of next year. And a 350-patient study recently began in Huntington's disease. (See BioWorld Today, July 31, 2009.)
Shares of Medivation (NASDAQ:MDVN) fell $1.06 Tuesday, to close at $25.04.