Published on Dec 09, 2022
Drug manufacturer Corcept (CORT) disclosed that late last year it received a records subpoena from the U.S. Attorney’s Office for the District of New Jersey, stating that the office was “seeking information relating to the sale and promotion of Korlym, Corcept’s relationships with and payments to health care professionals who can prescribe or recommend Korlym and prior authorizations and reimbursement for Korlym.”
The DOJ may be interested in the company’s efforts to grow sales of Korlym, its only FDA-approved product, by promoting its off-label use to doctors and recommending lower diagnostic criteria so more patients fit the narrow indication approved by the FDA, practices that appear to be ongoing, according to a Capitol Forum investigation.
Korlym is indicated to treat one symptom of Cushing’s syndrome, a rare disease that causes diabetes, fat accumulation in different parts of the body, high blood pressure, severe fatigue, and several other symptoms.
Only 10-15 people per million are affected by Cushing’s syndrome, which is typically caused by a hormone-secreting, non-cancerous tumor on the pituitary, adrenal gland, or occasionally elsewhere in the body that results in excess cortisol levels in the body. For most of those people, surgical removal of the tumor is the most effective treatment. Korlym, which can cost between $17,000 and $64,000 per month depending on the dose and can cause serious side effects, is approved by the FDA for the small number of people who have diabetes caused by Cushing’s and for whom surgical treatment did not work or is not an option.
These factors combine to create a very narrow market for Korlym. To overcome these limitations, Corcept may have tried to increase this available market for Korlym by lowering diagnostic standards for Cushing’s and promoting the drug for off-label use to treat people with obesity, diabetes, and high blood pressure who do not meet the standard diagnostic criteria for Cushing’s.
In addition to potential risk from the ongoing DOJ investigation, Corcept also states in its SEC filings that, “if the FDA were to determine that we engaged in off-label promotion, the FDA could require us to change our practices and subject us to regulatory enforcement actions, including issuance of a public ‘warning letter,’ untitled letter, injunction, seizure, civil fine or criminal penalties. Other federal or state enforcement authorities might act if they believe that the alleged improper promotion led to the submission and payment of claims for an unapproved use, which could result in significant fines or penalties under other statutory authorities, such as laws prohibiting false claims for reimbursement.”
Corcept did not respond to a request for comment for this article.
Regarding the investigation, Corcept says it is cooperating with the investigation and is providing documents faster than the investigators are able to absorb. “The truth is our friend,” according to the remarks of the company’s chief business officer, Charles Gary Robb, who said during the first quarter earnings call that Corcept wants to “get our story in front of [the DOJ investigators] as fast as we possibly can because I think that is how we will put this all behind us happily and be able to move forward without this distraction.”
“Paradigm Shift.” Around 2017, Corcept revamped its sales and promotion strategy to aggressively reach out to a wider universe of prescribers, such as non-specialist community endocrinologists and rural general medicine doctors who were less familiar with standard diagnostic criteria and treatment for Cushing’s, according to a former Corcept employee and allegations in a class action complaint, which relied on 14 confidential Corcept witnesses who described the company’s off-label marketing in 10 states.
Corcept filed an answer to the complaint and included numerous affirmative defenses.
The former Corcept employee told The Capitol Forum that “Corcept made our territories smaller and smaller and wanted us to go to primary care doctors.”
According to the source, Corcept sales representatives would encourage doctors to consider their patients with diabetes, obesity, or high blood pressure as possible Korlym candidates. Those doctors were encouraged to use a single test rather than the multiple diagnostic tests required to pinpoint Cushing’s, and to use a lower than standard diagnostic cut off level for that test to determine a patient has “sub-clinical Cushing’s.”
The lowered clinical diagnostic criteria pushed by the sales representatives, the source said, meant that more patients could be given a diagnosis of Cushing’s. However, as the source pointed out, true Cushing’s-related hypercortisolism is a sign of a hormone-secreting tumor, whereas less severe elevations in cortisol can be caused by stress or a variety of other conditions.
But, according to the source, the company crafted a marketing narrative that any elevation in cortisol was prima facie evidence of Cushing’s and began using the term hypercortisolism interchangeably with Cushing’s syndrome.
Corcept kept lowering the diagnostic criteria and saying “if the patient’s test results meet the company’s cut off, then they have elevated cortisol which means they have Cushing’s and should be on Korlym,” the former sales representative said, adding that “the way Corcept thinks is, as long as a patient meets Corcept’s definition of hypercortisolism, Korlym is warranted.”
Some of those other conditions that can increase cortisol levels, such as diabetes and obesity, also became conditions for which Corcept representatives promoted Korlym as an off-label treatment to lower cortisol levels.
“Managers would train you how to market off-label for obesity and for diabetes and to push doctors to increase the dose,” the former Corcept source said. “If you wanted to keep your job, you had no choice but to do it.”
“There was a lot of off-label promotion,” the source continued, referring to the drug’s promotion as a weight loss drug.
Managers, the source said, would conduct “ride alongs” with the sales representatives. The source, recounting their manager’s ride-along remarks, said “if you have a doctor who is known for treating diabetes, then they have to measure the cortisol of their diabetic patients and their obese patients. Then if it comes back at—Corcept kept lowering the level—then they’ve got to go on Korlym. You talk to the doctor. You say, ‘The reason your patients need to go on so high a dose of insulin is because of cortisol, so test them with this single test and prescribe Korlym if the test result is at or above a set level.’ That’s the level Corcept kept lowering. They would say that level was indicative of Cushing’s even though there was no evidence or diagnostic testing for the presence of a tumor.”
The sales strategy also called for diverting Cushing’s patients away from the standard course of diagnosis and treatment, which is locating the problematic tumor and surgically removing it if possible.
The LinkedIn profile of a former sales representatives notes that she helped to “drive a paradigm shift from surgical mindset to medical therapy option among endocrinologists and internal medicine providers” when selling Korlym.
But “there was never an indication for Korlym to supplant surgery,” emphasized the former Corcept source. “Surgery is curative. Korlym is not. Korlym does not stop the tumor from growing. So, in a suspected Cushing’s patient, if you are using Korlym instead of surgery, the tumor could continue to grow. A tumor that is potentially curable by surgery could possibly grow to the point that a surgical cure is no longer possible,” the source added.
Additionally, Korlym is not an innocuous medication. It can cause significant side effects, including moderate to severe nausea and vomiting, adrenal insufficiency, dangerously low potassium levels, abnormal thyroid function, and thickening of the uterine lining and prolonged, heavy vaginal bleeding.
Prescriptions shot up after strategy implemented. The effectiveness of this strategy can be seen in the high Medicare Part D prescription activity of some doctors in small towns, such as Dr. Norman Crabb, a family doctor in Ingleside, Texas formerly employed by WellMed, a primary care company.
According to data from CMS, Dr. Crabb, along with nurse practitioners in his office, prescribed 125 thirty-day Korlym prescriptions in 2020, 222 thirty-day Korlym prescriptions in 2019, and 327 thirty-day Korlym prescriptions in 2018, paid for by Medicare. The number of prescriptions paid for by non-government payers is not publicly available.
Less than 10,000 people reside in Ingleside, Texas. Given the prevalence of 10 to 15 cases of Cushing’s per one million people, the high prescription rates suggest that Korlym was likely prescribed for off-label use in the town.
A nurse who worked with Dr. Crabb told The Capitol Forum that doctors at the Ingleside WellMed clinic often prescribed Korlym for weight loss.
Texas is one of the 10 states the class action alleges off-label marketing of Korlym was confirmed by confidential witnesses. Additionally, one of the nurse practitioners who worked with Crabb gave a Corcept-hosted presentation in 2018 about the “clinical consequences of hypercortisolism.” held at Perry’s Steakhouse in Friendswood, Texas, according to a Corcept flyer for the event.
The Capitol Forum was unsuccessful in attempts to contact Norman Crabb. An online legal notice indicates that effective December 18, 2020 Dr. Crabb would no longer be practicing medicine at WellMed at Ingleside. WellMed indicated it would not comment on personnel matters.
Another example is Robin Anderson, a nurse practitioner who owns Upstream Health and Wellness in Portage, Indiana, population of 38,192. Upstream Health specializes in weight loss, hormones, and “cortisol issues,” among other health concerns, according to Upstream Health’s website.
Anderson prescribed 46 thirty-day Korlym prescriptions in 2020 and 55 thirty-day Korlym prescriptions in 2019 that were paid for by Medicare Part D plans. Corcept paid Anderson $20,503 in 2021, the first-year manufacturers were required to report payments made to nurse practitioners to the Open Payments database.
Upstream Health did not respond to a request for comment.
Off-label promotion appears to be ongoing. Optime is a specialty pharmacy and is the sole pharmacy that dispenses Korlym and collects payments from insurers. The Capitol Forum spoke with a former patient care coordinator at Optime Care who recently left the company.
The former Optime employee told The Capitol Forum, “I saw some physicians prescribe high dosages of Korlym for obese patients where it was obvious it was for weight loss instead of for Cushing’s related diabetes. When I would speak with some of these patients on the phone they would say, ‘I’m not diabetic. I’m just trying to lose weight and my doctor wants me on this medication to help with my cortisol levels.’ So, right there, it gives it away that it was for weight loss and not an actual diagnosis of Cushing’s diabetes.”
This strategy, as described by the source, continued even after the company received the records request from the U.S. Attorney’s Office.
According to estimates by both the Corcept and Optime former employees, at least 30% to 40% of Korlym prescriptions were prescribed for weight loss for obese patients who did not meet the standard criteria for Cushing’s syndrome, and many of those didn’t even have diabetes.
In the majority of those cases, the sources said the company relied upon two nonprofit organizations, The National Organization for Rare Diseases and the Patient Access Network Foundation, to pick up the tab for Korlym since insurance denied coverage.