Breaking Out with Breakthrough Drugs?

Upsher-Smith’s move into developing innovative drugs gained momentum in July 2008 with its equity investment of $6 million in Proximagen Neuroscience, a London-based firm that already had a new Parkinson’s drug called PRX1 underway. As Upsher-Smith takes several of the possible compounds through further development—clinical trials and commercialization under a licensing agreement with the U.K. company—its total investment, given milestone and royalty payments, could be as much as $232 million. The drug development component of that will reach as much as $125 million, Mark Evenstad estimates.

How does that compare to the costs of developing a branded generic drug? “It doesn’t,” he says. “A branded generic could cost anything from $3.5 million to $7 million.”

He expects PRX1 to reach the European and U.S. markets in 2016. “There’s been a lot of research over the past five to seven years, but new medications really have not shown up. [Parkinson’s] hasn’t been the major focus of any of the large pharmaceutical companies, mostly because physicians are very comfortable with L-dopa, which has been the standard of treatment for more than 30 years.”

With good reason, says Dr. John Nutt, director of the Parkinson’s Center and Movement Disorders Program at Oregon Health and Science University. Levodopa (also called L-dopa) is a substance naturally present in the body and a precursor to dopamine. The healthy brain produces dopamine to transmit signals that control the body’s movement. In Parkinson’s, dopamine production diminishes. But levodopa, which enters the brain and converts to dopamine, can compensate for the deficit and help smooth out tremors and movement difficulties as well as irregular sleep and other symptoms. Several manufacturers make levodopa drugs; Bristol-Myers Squibb’s Sinemet is one example.

“We have a lot of other drugs we can use, but to date, L-dopa is still the best,” Nutt says. That’s despite its downsides: a tendency to give less consistent relief—to turn on and off—as the disease progresses, and to cause mental confusion or involuntary movement as side effects. Still, Nutt explains, levodopa is preferable to dopamine agonists, another group of Parkinson’s drugs, and the rubric under which Upsher-Smith’s PRX1 falls.

Dopamine agonists (found, for example, in the drug brands Mirapex and Requip) mimic but don’t convert to dopamine in the brain. They’re thought to be less effective in reducing Parkinson’s symptoms than levodopa and more likely to cause negative side effects—which can include compulsive behaviors: gambling, overeating, sexual behaviors. “There’s still a lot we don’t know,” Nutt says, but the compulsions seem to derive mostly from agonists that act on a particular receptor in the brain.

Proximagen Neuroscience says PRX1 has shown evidence of giving more stable benefits than traditional levodopa. And Mark Evenstad calls PRX1 a brand-new kind of dopamine agonist.

“We’re looking at better ways to hit the receptors,” he says. “Say a receptor is shaped like a triangle and dopamine comes in shaped like a triangle as well. But what if you develop a synthetic compound shaped like a diamond that fits perfectly and has that ‘extra’ on the other side that could potentially be stored and reduce the ‘off’ time?”

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PRX1 will also be competing with other classes of Parkinson’s drugs, and with new gene and device therapies that are underway in R&D labs around the world. But if it’s successful, it stands to take at least a small piece of the Parkinson’s drug market, which currently tops $2 billion annually and is due to balloon with the wave of Baby Boomers now being diagnosed with the disease.