KORLYM, however, proved to be the early bet that turned the cards in Corcept's favor, making these additional discovery investments
possible. In contrast to the complexities built into a CNS indication, mifepristone's clinical potential for endogenous Cushing's
syndrome was recognized as far back as 1985, with more than 50 studies subsequently corroborating its effects.
"When we analyzed the science, it became clear that the controversy around the drug's separate profile as an abortifacient
was inhibiting interest in its application to Cushing's. The political baggage was very similar to thalidomide," Belanoff
said. "Yet any rational analysis would have to balance that against the high level of efficacy documented in the studies as
well as the sheer need—the medicines chest for Cushing's was flat empty."
In fact, the one drug that was in common use, ketoconazole, was under scrutiny for cases of liver damage after long-term exposure
Fast work from FDA
In 2007, Belanoff and his scientific team initiated a conversation with FDA staff on mifepristone as a treatment for Cushing's,
receiving an unexpectedly positive reception. In rapid order, the company secured orphan-drug status for the proposed indication
in treating Cushing's with type 2 diabetes—the FDA estimated the eligible population at around 5,000 patients—followed by
the filing of an NDA and request for Priority Review, in April 2011.
The NDA package included the results of a 50-patient trial, in which mifepristone delivered "significant improvement" in blood
sugar control along with marked reductions in insulin requirements. A REMS proposal was also included to address the dangers
associated with the drug's alternative use as an abortifacient. However, when the FDA approved registration status for the
drug 10 months later, it decided a full REMS was not necessary because of the small number of physician prescribers and the
company's pledge to maintain tight control of distribution through a single designated specialty pharmacy, Dohmen Life Science
Services. There is also a post-marketing requirement to report use data (age, sex, dose, and duration) and, of course, any
KORLYM made its debut only two months after marketing authorization, in late April 2012. The quick start was aided by the
company's advance work on a REMS package; though it turned out it was not needed for approval, the preparation forced management
to focus on something that proved critical to building the brand: the patient context. It was noted early on that endocrinologists
are very test-oriented in treating Cushing's.
"Because diagnosis is so difficult, repeated testing is the profession's stock in trade, because surgery is the default option
once diagnosis is confirmed," Commercial Operations Director John Lyons told Pharm Exec. "We recognized a stronger patient voice was needed to move drug therapy forward in the treatment discussion."
A patient-centric approach also made sense from the clinical perspective. "In Cushing's, every case is unique," says Corcept
Chief Commercial Officer Steve Lo. "There is the bewildering multiplicity of symptoms, which also vary by degree, as well
as individual variations in relapse rates, which can be high when initial surgery fails, leading to scattershot measures involving
additional surgeries, radiation, off-label use of other drugs, or outright removal of the adrenal glands —there is no standard
According to Lo, this heterogeneity required substantial investment in a different kind of sales force, one with the practice
familiarity and the scientific skills to market KORLYM almost on a case-by- case basis. "The clinical inertia around this
disease is intense," Lo said. "We couldn't take the approach of a 30-second detail with the boilerplate message KORLYM is
the right drug for your patients."