Medivation CEO David Hung is a persuasive individual.
He has negotiated some of the most lucrative drug development collaborations in biotechnology. Pfizer's $225 million upfront for Dimebon remains one of the marquee deals of recent years--if you look strictly at the dollars on the table and not at the disastrous data that followed. To gain global rights to MDV3100 for advanced prostate cancer, Astellas was persuaded to offer $110 million upfront with promises of $655 million more--$355 million ahead of a launch--along with a profit split.
Now that Dimebon has flunked back-to-back Phase III studies, the spotlight at Medivation ($MDVN) has shifted squarely to MDV3100. And Hung has used all the persuasiveness he can muster to make a compelling case that the drug has a solid shot at capturing a big chunk of the market for castration-resistant advanced prostate cancer, even after the approval of J&J's abiraterone three weeks ago.
Of course, persuasiveness will only get you so far in biotech. Long-term success relies entirely on the data and regulators' evaluation of the numbers and trials. In this case, Hung also faces a brisk dispute among the analysts who follow his company, over whether MDV3100 can not only deliver promising data versus a placebo plus standard care, but also come out swinging against abiraterone, which costs $40,000 for eight months of therapy.
One of the bears, Brean Murray Carret & Co analyst Jonathan Aschoff, told Reuters recently that, "it is not our view that MDV-3100 cannot succeed against placebo in vacuum; it is instead our strong view that MDV-3100 can only succeed clinically in a world without abiraterone."
Both abiraterone and MDV3100 are designed to do the same thing: remove the fuel for the disease from the equation. Abiraterone does that by inhibiting an enzyme needed for the production of testosterone; MDV3100 blocks the androgen receptor to prevent cancer cells from reacting to testosterone. Both drugs would be reserved, at least initially, for patients who are not responding to currently used surgical and therapeutic interventions.
MDV3100 has an impeccable scientific pedigree. It was discovered by a team of scientists led by Charles Sawyer, an investigator with the Howard Hughes Medical Institute based at the prestigious Memorial-Sloan Kettering Cancer Center. Sawyer also discovered ARN-509, an earlier-stage anti-androgen treatment at Aragon Pharmaceuticals, which he sometimes refers to as the Son of Medivation.
Starting with a compound that had already demonstrated an extraordinarily high binding affinity with the androgen receptor, Sawyer recently told Sally Church in a fascinating Q&A posted on her Pharma Strategy Blog that the team looked at more than 200 derivatives before they came across MDV3100.
As Sawyer explains, abiraterone targets the Cyp17 enzyme, which the body relies on to create testosterone. "Abiraterone is looking great," he told Church, "and showed a survival advantage in the same kind of trial as the Medivation one." At some point, he added, abiraterone and MDV3100 will probably be matched in a combo drug trial, offering an approach to tackle the disease at two different points.
For now, though, Hung is already well into a Phase III trial, which will wrap early next year with a possible announcement on interim results toward the end of this year. And faced with a competing drug, the CEO's immediate task is to explain why he thinks MDV3100 is the superior treatment.
Researchers for the company have spelled out a key advantage over bicalutamide, the standard anti-androgen in a pre-abiraterone world, noting that MDV3100 blocks testosterone binding to the androgen receptor, impedes the movement of the androgen receptor to the nucleus of prostate cancer cells and inhibits binding to DNA.
"We believe that redundancy is always a good thing in biology," says Hung. Comparing MDV3100 to abiraterone, he also zeroes in on the need to use prednisone, a corticosteroid linked to high blood pressure, with J&J's new drug. Prednisone presents a potentially serious safety issue for the men taking the drug.
MDV3100 "doesn't affect upstream hormones that cause high blood pressure," says Hung. "Abiraterone does not have an affect against (androgen receptor) splice variants," he adds. "3100 did block splice variants, and very effectively."
Bottom line: "If we had the same survival benefits as abiraterone without the steroids it would be a significant advantage."
The back-to-back Dimebon failures obviously cast a pall over Medivation. But Hung acknowledges the disappointment while holding on to hope that a final Phase III will come out in its favor. Significantly, he says, this last study involves 12 months of treatment versus six months in the first two, giving Dimebon a better chance to finally beat out a placebo.
"It will only take a few million to complete the study," he adds, and Pfizer is absorbing 60 percent of all development costs. -- John Carroll (twitter | email)