MIFEPRISTONE, BETTER KNOWN AS RU486, IS ONE OF THE MOST CONTROVERSIAL AND politically charged drugs ever approved. To abortion opponents, it does the unthinkable: It stops the creation of a human
being. But researchers at Corcept, a small pharmaceutical company based in Menlo Park, California, believe the drug represents
much more. To them, mifepristone is potentially
Corcept CEO and co-founder Joseph Belanoff
- the first therapy specifically targeted at psychotic major depression (PMD), a disease that affects more patients than either
schizophrenia or manic depression, and leads to suicide in approximately 15 percent of patients;
- the first psychiatric treatment intended for acute, episodic use in a therapeutic area where patients often rely on perpetual,
daily medication—often throughout their entire lives;
- a major step forward in drugs based on the concept of regulating cortisol, the "stress hormone"—which could lead to treatments
in conditions as diverse as Alzheimer's disease and weight gain associated with the use of antipsychotic drugs.
Corcept has a long way to go to prove to FDA that Corlux, its mifepristone product, works. The early-stage trials were promising,
but the first of its three Phase III studies produced disappointing results. Corcept is soldiering on with its two remaining
trials, as well as with a separate study, funded by Eli Lilly, involving weight gain. Even if studies of Corlux fail to meet
critical endpoints, the tests might still provide clues to improving the current arsenal of treatments for psychosis.
The field of drug development is rife with examples of old drugs being used for new purposes. But Corlux is the exact same
drug at the exact same dose as Danco Laboratories' Mifeprex, one of the two pills used to induce a medical abortion. If it
successfully completes Phase III trials, the drug could face more than the usual regulatory challenges, and Corcept's management
team will need to respond to concerns about access and distribution.
They say they're ready. They say that the drug's controversial past is actually an opening for company executives to spotlight
what's truly unique and innovative—not just sensational—about their product.
PMD is a disease in which severe depression is laced with episodes of delusions, hallucinations, anxiety, and insomnia. Though
it affects approximately three million people—about 20 percent of those who suffer major depression—and can lead to strikingly
bad outcomes (patients with PMD are 70 times more likely than the general population to kill themselves), it is not well known.
CFO Fred Kurland believe that mifepristone, or RU486, might one day treat psychotic major depression.
"Most people have never heard of [PMD]," says Fred Kurland, Corcept's chief financial officer. "But most people in this country
have heard of the case of Andrea Yates, the woman in Texas who, while suffering from an episode of this disease, unfortunately
drowned her five children. It was not only a bad ending for her and her family, but it just displayed yet again the inadequacy
that psychiatry has in dealing with this disease."
Psychiatrists often try a combination of antidepressants and antipsychotics to address the disease symptomatically. When those
options fail, their next best hope is several treatments with electroconvulsive therapy (ECT), which is administered under
general anesthesia and carries significant risk.
Still, while psychosis is the hallmark of the disease, patients experience only a median of three to five episodes over the
course of a lifetime. And that profile makes treating PMD akin to treating an infection, Kurland notes.
"PMD is not a chronic disease like, say, schizophrenia; it's an episodic disease," he says. "Now, the episodes are very severe;
they last anywhere from six to 18 months. And they are the primary cause of all suicides and homicides that occur. But, interestingly,
if you get through an episode...you could be well."