Born Again - Pharmaceutical Executive

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Born Again
Mifepristone is best known as an abortion drug. But it appears to be on the verge of a second career—treating a severe form of major depression.


Pharmaceutical Executive


If the product is approved, Corcept will handle sales, marketing, and distribution in the United States, hiring about 35 sales reps to focus on the 300 or so hospitals that offer ECT. It also plans to work with FDA to closely monitor how the drug is dispensed.

Giving psychiatric patients mifepristone isn't controversial in and of itself. Neither men nor women experienced any reproductive side effects in a study of 250 patients, Kurland notes. One of Corlux's trials even included a nun, he adds. "People get it—you don't ban scalpels because they can be used to kill people." But like Mifeprex, Corlux would be administered under observed dosing guidelines, and women would be required to fail a pregnancy test before receiving it. As Kurland points out: "We don't want to be—even inadvertently—in the abortion business."

Yet controlled distribution could prove to be an advantage to Corcept, because it discourages generic competition, notes Sanchez.

Even if Corlux's trials do not meet their necessary endpoints, Kurland notes that the company was built around the study of the GR2 receptor and its antagonists, not mifepristone, which is off patent. Corcept's own patents, some of which are licensed from Stanford, cover the use of GR2 antagonists to treat disorders such as early dementia, stress disorders, mild cognitive impairment, psychosis associated with cocaine addiction, and weight gain associated with antipsychotic medication. The next evolution of the company's research would involve finding a compound that can block GR2 without blocking progesterone—with the hopes of one day treating disorders ranging from post-traumatic stress disorder to post-surgical delirium.

NEXT GENERATION DRUGS

Cortisol, moreover, doesn't just play a role in stress. It also acts as an insulin sensitizer. In animal studies, rats that were given Corlux in combination with the antipsychotic drug Zyprexa (olanzapine) were able to avoid the weight gain that is a common side effect of that product. They also lost weight that they had put on after taking a course of standalone Zyprexa.

Eli Lilly, Zyprexa's manufacturer, is now partnering with Corcept to fund a proof-of-concept study that would test whether it's possible to develop an antipsychotic that avoids severe weight gain. Patients on antipsychotics gain an average of two pounds a week—worrisome enough for FDA to require a black-box warning about diabetes on package labels. Corcept also counts five additional companies that market antipsychotics containing the same warning.

Eli Lilly has no intention of marketing Corlux as a concomitant therapy to Zyprexa. Rather, the study will help the company understand whether GR2 antagonists can mitigate weight gain, which might not even be caused by the drug itself, notes Carole Puls, a spokeswoman at Eli Lilly. "There's been no research that draws any conclusion in that regard," she says. "We just want to understand the how and why, and how we can lessen this [side effect] in the future. You want to make sure you're treating the patient holistically."

The results could also show that there is life for Corcept beyond Corlux's Phase III results. The financial future of a still-productless company is always uncertain—but, confident, Corcept will seek funding to continue trials in 2007. And the company's researchers plan to pursue additional proof-of-concept studies, to move forward the next generation of pre-clinical compounds.

Sanchez wants to see more evidence beyond rat studies—but is cautiously optimistic about Corcept's future prospects. "You shouldn't assign too many expectations until there's more clinical data," he says. "But if it's positive, it's huge."


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