Corcept Therapeutics: The Company That Perfectly Explains the Health Care Crisis

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If someone wanted to use a Venn diagram to illustrate what is wrong with the U.S. health care system, picking the different sets would be easy: Price gouging, abuse of loopholes, hidden risks to patients, baffling regulatory decisions, marginal efficacies and the use of doctor payments to stimulate drug sales would be some logical choices.

And a case in point would be Corcept Therapeutics, a specialty pharmaceutical company based in Menlo Park, California, and the apparent union of all things expensive and opaque. So how did Corcept, a small company with just one drug aimed at treating a tiny population of patients with a rare pituitary disorder, wind up there?

Corcept has managed to make handsome profits by quietly yet efficiently exploiting gaps in the nation’s health care regulatory framework. And its sole drug is none other than the storied mifepristone, better known as the abortion pill. While Roussel-Uclaf developed mifepristone in France in 1980, it became famous in the U.S. in 2000 when the Food and Drug Administration ruled that doctors could prescribe it to induce an abortion; it was sold as RU-486.

Just before that, two doctors at Stanford University Medical School’s psychiatry department began examining mifepristone for quite another use. In the mid-1990s Dr. Joseph Belanoff began testing a longstanding hypothesis of then-department chairman

In addition, the fact that the Orlando VA Medical Center generates so many Korlym prescriptions is rather curious. The patient base of the VA’s medical system nationwide has in recent years been more than 91 percent male, according to the department’s analysis of those using its services from 2006 to 2015. But Cushing’s syndrome typically occurs in women rather than men, by an almost 5-to-1 ratio, according to the National Organization of Rare Disorders.

Susan Carter, a VA spokeswoman, did not reply to several calls and an email seeking clarification about Dr. Yau’s prescribing of Korlym and compensation for serving as part of Corlym’s speakers bureau.

Update: This story has been amended to include two paragraphs discussing the natural limitations of the FDA’s Adverse Events Reporting System and the Southern Investigation Reporting Foundation’s approach to reporting with this data.

45 thoughts on “Corcept Therapeutics: The Company That Perfectly Explains the Health Care Crisis

  1. Who payed you to write this article?

    The short percent in CORT is 25 % and article like yours are design to depress the stock price. If things had been as bad as you describe it, the police would be involved and the CEO would have been in jail.

  2. This is not True and government cannot keep it going for longer term. This is ridiculously wrong. This Article seems to be designed to cause problems for CORT.

  3. This article is hysterical. Astounding how many misrepresentations are littered in this piece of “investigative journalism”.

    Also – if the market segment is so small. And the drug really so marginally effective, why is TEVA in the midst of a lawsuit with this company to bring the generic to market ASAP.

    Come on people – think before you let someone like Roddy and his clown shoes aptitude influence your investment decisions.

  4. What a load of crap. Where did you get this info from? And who PAID YOU?? Do you really think that corcept just got some pass from theFDA because they’re special? And all the deaths you claim from this drug – please show us where you got this. Shame on you for this irresponsible reporting. Investigate journalism at its worst. Laughable and transparent.

  5. I read the report carefully. The author presents nothing but guess work. He has no any evidence to show Korlym is ineffective. Rather, he cites something else, which in my opinion, to vilify Korlym.

    Let’s look some what he said.

    “its sole drug is none other than the storied mifepristone, better known as the abortion pill.”
    “two doctors began examining mifepristone for quite another use that mifepristone could block the body’s production of cortisol and be used to help treat episodic psychosis”

    We can interpret that mifepristone has other medical functions besides abortion.

    “Indeed, the FDA approved Korlym based on a single open-label study consisting of one group of 50 patients.”

    The author doesn’t provide any reference of it. Well, assume it is right. That means FDA think it’s sufficient study for Korlym.

    In regards to FAERS, the report have detailed what Cort’s CEO explanation which perfectly make sense.

    The vast part of report is questioned Cort’s marketing strategy. Well, there is nothing wrong for Cort to partner with local doctors. I’m Accountant, and from time to time, I am approached by accounting software providers who want me to partner with them. It’s entirely legal and normal business practice.

    The key issue of the report is it doesn’t present anything to prove Korlym is ineffective. Readers should not be fooled.

  6. Mr. Tunston,
    Your views of me are your own and I won’t engage with them, but you did lay out two specific concerns regarding this story: A) (the lack of) evidence re: mounting deaths and B) that my assessment of the FDA testing procedure was problematic.

    I laid out in detail where I got the deaths from: the FDAs adverse events reporting system (FAERS). The snapshots on the “37” and “17”? That’s where I got them.
    It’s located here: https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/ucm070093.htm

    Enter: Korlym and click through. You’ll see I didn’t count 42 deaths that upon further investigation were clearly not drug-related. This is public data.

    Regarding the FDA’s investigation of Korlym: Being skeptical of an open-label, single-arm, non-blinded test with 50 participants is not harsh or unfair. That is simply acknowledging that this drug was in no way investigated with the rigor that other drugs were –and are — subjected to. The FDA approval package, which was linked to, is full of numerous examples of this being an unusual investigation. Moreover, that should be considered alongside the European Medicines Agency blunt rejection of the drug over concerns of ineffectiveness on the targeted population. These details were linked to in full.

    Perhaps this helps.

  7. Jerry,
    Mifepristone indeed has another medical applications beside abortion — its use in treating Cushing’s syndrome (an earlier attempt to treat depression proved both controversial and unsuccessful.) The FDA documents: the approval for the Orphan drug application, the formal approval letter and the FDA risk assessment and remediation document, are all linked and all of them cross-reference these points with each other.

    There is simply no way around the fact that its trial was exactly as described: 50 patient, open- label, non-blinded, no comparator arm.

    I have no idea of the rules of disclosure required to maintain your CPA, but an MD is a bit different. There’s nothing wrong at all with a pharmaceutical company seeking — and paying for –physician input, and as I wrote, speaker’s bureaus serve a real purpose. But most people would want to know if their MD is in the end working for them, the patient, or some other company because of motives. I don’t want my MD to give me a script because she has a monthly quota to fill; I want her writing it because her view is it’s best for my health.

    Additionally, regardless of what we think, the federal government mandates that those MDs who have a commercial relationship have to disclose it to CMS. None of the MDs who did many dozens of speaking gigs for Corcept (including sometimes 2x/day) are doing any research for the company.

  8. I am SO thankful for this article, Roddy. I run a patient support group for Cushing’s patients, and I have been highly skeptical of Corcept and their aggressive marketing of this drug. We’ve seen many Cushing’s patients given Korlym and subsequently have major side effects. One almost died; she spent months in the ICU in liver failure. It sounds as if your detractors here are only investors, and not medical personnel, so their comments are the way to try to pump up the stock price. I happen to be worried more about my patients’ health!

  9. Thanks Roddy for your reply. A couple of points here.

    1. You do agree that Mifepristone indeed has another medical applications beside abortion. But at your very front part of report, you state “its sole drug is none other than the abortion pill.” This is very misleading.

    No many people are patient enough to read the whole report. They may just read stop here and regard Korlym as abortion pill, which is entirely not true.

    2. FDA only selected 50 patients for study and then approved Cort’s application. That’s the fact. But as your report mentioned, the number of patients for taking the drug treatment is only 5,000 in entire nation. 1% of sample is not that bad.

    Plus “A separate open-label extension of this trial is ongoing. Additional evidence supporting the agency’s approval included several safety pharmacology studies, drug-drug interaction studies and published scientific literature. Patients experienced significant improvement in blood sugar control during Korlym treatment, including some patients who had marked reductions in their insulin requirements. Improvements in clinical signs and symptoms were reported by some patients.”

    You can see the above from: https://www.drugs.com/newdrugs/fda-approves-korlym-patients-endogenous-cushing-s-syndrome-3101.html

    Very important “A separate open-label extension of this trial is ongoing”, which means there is continuing study by FDA to monitor Korlym effectiveness. Given the fact that FDA hasn’t given any different opinions in regards to Korlym since initial approval in 2012, we can reasonably say Korlym is good for Cushing’s syndrome treatment.

  10. One should not make assumptions such as the one you implied. I for one am NOT an investor. Having said that you might want take this same rationale and apply it to the author of this article, perhaps you are not familiar with him.

    Are you a medical professional? I tend to wonder due to your reference to mifepristone and liver failure, which is not an adverse event related to this drug. Take your assumptions elsewhere

  11. Mike,
    I’m not an investor and no one affiliated with SIRF is either. The woman made a reference to someone she knew who was ill and expressed an opinion. You’ve established you don’t like me or the article — got it. So does everyone else. Please try and be constructive. Thanks.

  12. Jerry,
    I’m sincerely shocked that you (or anyone else) thought I implied that Mifepristone was solely for inducing abortion. I’m glad you read further on! And, hopefully, you see it wasn’t at all my intent to mislead. That said, I will be on my guard to avoid this apparent mistake in the future. Thanks for engaging. Best to you and yours, Roddy

  13. Agreed this article is laughable! Making claims with no solid evidence to back it up. Hopefully people with brain will see through this.

  14. I agree with you mike. I wish though who come across this have a brain and see through this. This article and some of the comments are laughable. No solid evidence except for hearsay stories. Thank goodness Facebook keyboard warriors aren’t the drs in charge.

  15. I AM that patient! I can assure you that prior to taking Korlym I had perfectly normal liver enzymes. Within 4 months I was hemorrhaging so badly that I needed two transfusions. I was virtually bedridden by month 6 vomiting multiple times a day, that my prescribing doctor ran a series of tests. At that point my liver enzymes were 3xs normal. I was told to stop the drug immediately. I went to a gyno in order to receive a hysterectomy, my liver and spleen were so swollen the had to perform the procedure open rather then laparoscopically. Once in surgery, due to the anesthesia my liver tilted. I spent 98 days in UPenn clinging to life. I was given last rights on Feb 13 2013.. it’s by the grace of God I’m still here, but I have significant fibrotic damage to my liver. The big wigs at corcept befriended me, asked me to be a spikes person, had me videotaped to tell my story to help bring awareness. Once I had adverse effects, they dropped communication with me faster then a speeding bullet! I went from hero to zero! Those early impurities?? Hmmm. Also, I happen to know that their prior failed, unreported studies might have had adverse liver side effects.. but conveniently for them, we’ll never know.

  16. Mike,

    Perhaps one of the problems with Korlym is that Corcept has not been honest about the various side effects. I assure you that liver damage is one of them … no matter what “adverse events” are listed.

  17. Why haven’t you disclosed in the article if you, your hedge fund father, associates, friends or family members shorted the stock before the article was printed? It’s suspicious that the stock dropped sharply the day prior to publication, while the general market was up. The SEC should look into this.

  18. Summary and analysis of the “inferences” made in the “hit piece”:

    Inference ( 1 ): that efficacy of the drug was not demonstrated because the trial consisted of only 50 patients and because a comparator arm was not used.

    Facts: Cushings is a rare disease. At the time of the trial, it was estimated that about 5,000 people suffered from the disease. It would be difficult to recruit patients for trial from this old and sickly population. The FDA determined that a trial of 50 patients would suffice to test the efficacy of the drug. The FDA also determined that a single arm study would suffice because it would be inhumane to have some patients, from this population, take a placebo.
    The FDA then determined that the trial demonstrated that the drug is effective. Doctors prescribing the drug also deem that it helps their patients.

    Conclusion: the author has no basis for inferring that the drug is not efficacious.

    Inference ( 2 ): that doctors were paid to prescribe the drug.

    Facts: Pharma companies pay doctors to promote drugs. Prescribing doctors are paid to speak at symposiums to recount their observations of patients using the drug. Doctors are paid to run studies. Doctors are paid to write research reports.

    Conclusion: Payments to doctors is not unique to this Company. It is a common marketing practice in the industry. Perhaps it can be argued that pharma companies should not pay doctors, or that former generals should not serve on the BOD of defense contractors or that former presidents should not accept $100K payments for speeches; but it is what it is.
    To single out one company and infer that the payments were illicit is yellow journalism.

    Inference ( 3 ): that a doctor in Virginia is prescribing Korlym off-label
    Facts: The author looked at a list of prescribing doctors ranked by the number of prescriptions written. He singled out the doctor at the top of the list, who works in a Virginia clinic; and points out that nearly 84 patients at the clinic during a three year period were prescribed the drug. He didn’t interview any of the patients but is making the inference that this doctor prescribed the drug to patients who did not need it.

    Conclusion: There is no basis to name a doctor that is the highest prescriber of any drug and infer that the doctor is prescribing the drug to patients who do not need it. According to the latest estimates, there could be 11,000 patients with Cushing’s. The state of Virginia contains 2.6% of the US population. So there could be 270 patients in Virginia with Cushing’s. Having 28 treated annually at this clinic doesn’t seem that out of the ordinary to set off alarm bells.
    The inference that the doctor is unethical is baseless. It makes the author look desperate trying to make a case while grasping at straws.

  19. Interesting is when the article was released …just timed during lunch time at the trading desks… this guarantees a large drop for the stock.
    Look at the sirf donation list in 2018, this tells me a lot of your work
    In my option this article was not helping patients it helped “unknown” people to make a lot of money.

  20. Sam,
    I have nothing to disclose; I am an established investigative reporter and no one affiliated with SIRF has an economic interest in what we write. Perhaps you should read the “About Us” tab and especially the “Donors” tab. There’s even a Primer for people like you, who see hobgoblins where none exist.

    My father Mike Boyd ran a convertible arbitrage hedge fund that closed in 2012. The hedge fund never did equity investing and most especially, never employed single-stock shorting. He is now retired, and devotes his time to travel and raising money to build out a soup kitchen back in Ct. (where I’m from.) His investments are in land/real estate, ETFs and one stock, $MU. Beyond that he is in cash. He’s never provided me a tip and I’ve never asked.

    You are free to dislike me, this article and SIRFs body of work (and/or my other reporting) for whatever reasons you choose. But bring up lies about my motives or family again? You are banned.

    This is the first and last time this gets discussed here.

  21. James,
    Comments are moderated. I’m just getting to them now. I hope this clears it up for you.

  22. Mike,
    Not sure what your relationship with Korlym is, or how you know so much, but liver failure IS in fact a side effect of taking this drug. I took it for 2 months, and it made my symptoms even worse, so I stopped taking it. I do have Cushing’s AND Diabetes so I was a prime patient for them to test it out… I will warm ANYONE to stay away from this drug!

  23. On what basis are you saying that Cushing’s patients are “old” and sickly. I agree we are sick, but like any other disease, there are various levels of sickness and functionality. Cushing’s affects all ages, including children. It’s not as common, but people of all ages are fair game when it comes to Cushing’s.
    If you’re going to try to correct someone, make sure you aren’t misspeaking while doing it.

  24. This is the same drug that christine blasey Ford performed research. Same company

    If she has a financial stake in this I would not trust it

  25. I have no affiliation with korlym. I think you may have this drug confused with a well recognized cortisol lowering drug that has a box warning for this issue. The FDA does not look the other way for Corcept, they just don’t get a pass. I’m sure there are some one offs with any drug or other medical issues going on (known or not) that play into issues but there is no basis in fact regarding this drug and liver failure.

  26. Mr. Boyd,

    I find it particularly interesting that you fail to mention the Support Program for Access and Reimbursement for Korlym (SPARK), Corcept’s charitable program that provides Korlym for patients that cannot afford the drug or do not gain prior approval from their insurers. Further, the ~150% price increase of Korlym since 2012 does not mark a significant deviation from other specialty pharmaceuticals for the given time period. Obviously, when used out of context like in this article, the figure seems excessively high.

  27. I really see nothing interesting or compelling about the “clustering” of scripts coming from any particular geographic location. Patients do not have to live in any particular city in order to see any doctor – most probably these drs have a lot of experience treating cushings patients and therefore the number they see is much higher; patients will go to the moon to try and find a dr that’s saavy about this condition – it is one of the most challenging endocrine diseases there is, if not the most. Many endocrinologists see ZERO cushings patients in their entire career, some see enough to be dangerous and know so little that patients end up going from one dr after another to find a knowledgeable one who can/will help them. It’s extremely concerning the number of endocrinologists that do NOT know how to diagnose nor test for cushings, eg thinking they can rule out with a test or two. There are not just experienced drs in every town that patients can avail themselves.

  28. Mike,

    Are you REALLY telling two people who almost DIED from a prescription drug that they are confusing the two drugs? I assure you, I know these women and know that they know more about Cushing’s and any available treatments than most of the Corcept employees. The drug you are speaking of is ketoconazole, an anti-fungal that has been used for many years to lower cortisol levels. It does have a black box warning, and it has been shown to adversely affect liver enzymes. Why does it have this warning? Because it went through the proper testing procedures, and has continued to be monitored over the years. The black box warning is specific to prescribing for dermatological issues for which there is no other appropriate anti-fungal. The question is really this — why does Korlym not have a similar black box warning? The number of adverse hepatic events is not a low percentage of users of the drug.

  29. Susan are you really suggesting that korlym has not been held to proper testing and reporting protocol since it came to market almost 7 years ago? I’m sorry but the FDA just doesn’t turn a blind eye to anyone. And while I’m sure these folks know a lot about their illnesses I certainly do not believe they know more about the science and mechanisms behind this drug than the researchers and scientists. I’m certainly very glad they’re fine, but let’s keep this sensible.

  30. ..and the black box warning for keto is NOT only specific to derm uses – it’s specific to all uses – your liver doesnt know the difference. That’s the end of this discussion for me – too off base and way too medically incorrect. Feel free to respond if you feel you need to but I’m not going to banter with you anymore.

  31. I also, along with Susan, have seen many suffer and some die from using this product. The question I have, however, is why use it at all? It is not a long-term solution to hypercortisolism. The source still needs to be found and, for long-term, surgically removed. There are no other alternatives for long-term solutions. Why use this potentially devastating drug at all?

    Bilateral adrenalectomies and transphenoidal endoscopies have excellent outcomes for patients with much less chance of morbidity and mortality when done by surgeons who have experience doing them.

  32. An article from Bill Koski from Seeking Alpha released 28.02.2019

    The Southern Investigative Reporting Foundation published a report Friday on Corcept Therapeutics.

    The report implies that rising deaths among patients on Korlym are related to off-label prescription and that Corcept is encouraging overprescription by compensating physicians.

    CORT traded down as much as 15% on Friday in the wake of the report.

    I argue that the report missed the mark, falling short of sophisticated analysis and mischaracterizing circumstantial evidence.

    The other day, the Southern Investigative Reporting Foundation (SIRF) published a report on Corcept Therapeutics (CORT). Corcept Therapeutics is a small pharmaceutical company that markets Korlym (mifepristone) in a rare disease called Cushing’s Syndrome, a condition that results from excessive exposure to the cortisol.

    In this report, the author vilifies Corcept as an example of some of the leading problems in American healthcare. Although SIRF maintains they are free of COIs related to short-sellers, the report reads more like an exposé by a short seller rather than an honest piece of investigative journalism. The tone of the article misconveys the author’s intent; where I had hoped that the piece would be a well-constructed criticism of ethical concerns in the drug development ecosystem, I find that the research lacks substantive analysis, and the rhetoric misdirects the reader in an attempt to stitch together a cohesive narrative. The evidentiary standard falls short in many cases, leading to speculation and insinuation where I had hoped to see a compelling analysis.

    Sadly, I think the author misses the opportunity to construct a more thoughtful dialogue on the ethical problems faced by the healthcare system in an attempt to capture shock and awe.

    I want to highlight the relevant ethical points here so that the reader can keep these in the context of my responses to the original work.

    Drug pricing can prohibit patient access to important treatments and exploit patients in high-risk populations
    Regulatory leniency allows more treatment options in small patient populations but risks setting the bar too low
    Financial conflicts-of-interest among physicians affect the integrity of prescribing decisions and clinical literature
    In this article, I contend that this report has little to no read-through for Corcept’s share price. Markets often behave very inefficiently with small- and mid-sized biotechnology companies. Corcept is one example of a small biotech with an inefficient share price. The inefficiency of Corcept’s share price results in large part because the company is difficult to fit into an easy to digest “box”. Consider that Corcept:

    Is a rare disease company with an approved treatment for Cushing’s disease and a next-generation treatment under development; and
    Is a revenue-stage company with a positive and growing bottom line; and
    Has multiple clinical stage development programs in oncology, NASH, and psychiatric indications.
    This odd combination of factors attracts an unconventional class of investors that has historically led to inefficiencies in the company’s share price. The company tends to attract rare disease investors and institutional investors attracted to Corcept’s bottom line. Interestingly, Corcept’s development programs are largely overlooked by the oncology crowd because hormones are not vogue.

    Here, I will comment on the most prominent points raised by the author.

    Korlym received FDA approval on a potentially inadequate clinical trial
    The author asserts that:

    The fact that the FDA had granted an approval allowing the company to market Korlym, however, doesn’t mean Corcept had scientifically demonstrated the drug’s success in treating Cushing’s syndrome.”

    The author goes on to state that the FDA concluded the trial was flawed:

    The FDA’s risk assessment and risk mitigation review for this study did conclude that Korlym’s trial design was flawed without the testing of an approved comparator drug”

    This turns out to be a gross misrepresentation of the FDA’s assessment. Here, I reproduce the exact language used by the FDA in the report cited by the author:

    “The open label and uncontrolled nature of the trial can introduce confounders, biases, and limitations that are often mitigated through the conduct of a randomized, double-blind, and controlled clinical trial.”

    It takes a stretch of the rhetorical imagination to construe that the FDA indicated this was a flawed trial. There are very real and very relevant criticisms of single-arm, open-label trial designs. At the time, the FDA clearly cited that a randomized controlled trial was not possible and made the decision that the potential benefits of Korlym approval outweighed the associated risks.

    The author further cites that:

    An open-label study is the least rigorous type of scientific investigation”

    Which again is a misrepresentation. An open-label study is unequivocally less rigorous than a randomized controlled trial, which is the gold standard in clinical medicine. However, an open-label study can prove substantially more rigorous than many other scientific investigations, such as a retrospective or case-control study. In this case, the FDA allowed the single-arm study because it was gauged to be the next best option where an RCT was not deemed viable.

    Regardless, this discussion is now seven years old and soon to be obsolete. Relacorilant, Corcept’s successor to Korlym, which has been designed to be more potent, while minimizing adverse side-effects such as pregnancy termination, is being studied in a pivotal ongoing Phase III trial that is double-blinded and placebo-controlled. The results of that trial, expected in 2020, should help eliminate ambiguity about the activity of glucocorticoid receptor modulation in Cushing’s. The future of the company is about Relacorilant, not Korlym.

    Patient deaths on Korlym
    Here, the author insinuates that an increase in 2018 in deaths among patients using Korlym could be related to off-label usage of the product.

    “Asked about the recent sharp increase in the number of deaths recorded for Korlym in the FDA’s adverse events reporting system (FAERS), to 37 in the first nine months of 2018 from 17 for all of 2017, Robb was adamant that none of the deaths could be directly attributed to Korlym. In response to a question about how he could be certain of that, he said, “All [the FAERS death reports] are adjudicated by a third party”: Robb added that Corcept retains Ashfield to provide pharmacovigilance, a service that evaluates reports of a drug’s adverse events for a manufacturer. And he insisted that the medicine and its dosage were not responsible for any of 103 deaths reported for Korlym since 2012. He did not answer a question about why 17 of the 103 death reports mentioned “product used for unknown indication.”

    The author’s work here lacks substantive analysis. To start with, there are a number of limitations to data in the FAERS database reported by the author. Firstly, the FDA states UP FRONT that there are duplicate and incomplete reports in the system, that information in the reports has not been verified, and that rates of occurrence cannot be established with these reports.

    Furthermore, the reports referenced by the author are analyzed based on when the report is received, not when the incident occurred. Segmenting by when the incident occurred, only 26 deaths were reported as occurring in 2018. The rest occurred in a previous year or contain missing data.

    Raw event data from FAERS database

    Finally, the author inappropriately cites a reference to absolute death counts. With an increase in the number of patients treated with Korlym each year and a proportionally larger increase in the number of patients previously treated with Korlym, it is reasonable to expect some increase in the number of deaths reported each year in patients treated with the drug.

    A more useful statistic would be to report the number of annual patient deaths per year as a percentage of all patients treated with Korlym. Taking one look at the FAERS data, it is clear that some of the reports are incomplete. After a third party with expertise in pharmacovigilance reviewed and cleared each case, to cite “product used for unknown indication” among patient death reports and imply this in some way comprises negligent corporate conduct is inappropriate.

    Cushing’s disease is a dangerous disease – as stated by the FDA, most patients die within 4-5 years without treatment. As highlighted by the Corcept CFO, some of these patients are taking as many as 20-30 medications concurrently. There are many potential confounds that make a brief glance at raw data from an incomplete database inadequate.

    To claim that deaths among Korlym patients are rising, and to imply that these deaths are related to the drug, is sensationalizing inadequate data.

    The relationship between individual prescribers and Corcept Speakers Bureau compensation
    Here, the author sneaks in a couple of points. Firstly, the author notes that speakers’ bureaus are a legal practice whereby physicians receive compensation for professional activities discussing the use of the drug. The author also notes that these arrangements can devolve into quid-pro-quo relationships, an important conflict of interest in pharmaceutical marketing and sometimes illegal practice.

    As it relates to Corcept, the author observes that many of the physicians writing the most prescriptions for Korlym have practices in rural settings with a reduced population and suspects that these providers could be overprescribing Korlym by including patients with diabetes and not just Cushing’s. Cushing’s disease, after all, is a rare disease, and it would appear unlikely that we see more prescriptions occurring in a rural setting where there are less likely to be as many patients, as compared with larger, centralized institutions.

    Source: SIRF report

    I present an alternative thesis that is not mutually exclusive with all of the author’s original points but nonetheless tells a less insidious story.

    Korlym has faced significant challenges with uptake in rural, predominately conservative, pro-life areas. Korlym, aka mifepristone, is well-known as the abortion pill. While the drug is used effectively to manage some of the effects of excessive cortisol in Cushing’s, pregnancy termination remains a controversial side-effect. Resistance to prescription is exacerbated by the demographic of Cushing’s patients. As the author notes in an unrelated discussion, Cushing’s occurs more frequently in females than males by a factor of five, where pregnancy termination is a viable concern. Many physicians may refuse to adopt Korlym because of personal pro-life beliefs.

    Interestingly, when you look at the political representation for the districts containing top, individual Korlym prescribers, we see that the clear majority of them fall in conservative districts.

    Political representation for districts with top individual Korlym prescribers

    Source: Publicly available political information

    Sure, it is unlikely that Zanesville, OH, organically saw 39 patients in their 25,000 person town present with inoperable Cushing’s. However, consider that Dr. Mohammad Ijaz could be the only practicing endocrinologist in the region that (1) has experience tackling a difficult diagnosis, (2) has treated hypercortisolism with Korlym in the past, and (3) is ethically willing to prescribe a drug known to cause pregnancy termination. Tack on the fact that Cushing’s disease is rare and exceedingly challenging to diagnose, and is it really all that surprising to believe that some specialty providers may receive more patients?

    I also learned a few interesting tidbits after spending hours parsing through patient forums and reading testimonials:

    Cushing’s disease, diagnosed or undiagnosed, is devastating in terms of quality of life
    Many patients initially struggled to receive an accurate diagnosis, in part due to biases by physicians against diagnosing a rare disease
    Patients sometimes travel substantial distances to receive evaluation or treatment
    In light of all this, there are many ways to question the data presented by the author. Do the top prescribing physicians prescribe Korlym because they receive Honoraria from Corcept? Does Corcept pursue speakers for the bureau because they are top Korlym prescribers? Or perhaps, do industry leaders both attract the most patients to their clinic and represent prime candidates for the Corcept speakers’ bureau?

    Further, are these physicians illegally or amorally overprescribing Korlym in exchange for $10,000 in Honoraria? Sure, financial conflict of interests are insidious and can materially affect a physician’s practice. For context, the average endocrinologist makes $225,000/year, so it is reasonable to suggest that these figures – ranging from a couple hundred dollars to $50-75,000 in extreme cases – could represent fair compensation. Salary: Endocrinologist

    On one hand, you can make the argument that any amount of compensation is too much. Personally, I think it is a reasonable business strategy to use legal, professional avenues to promote awareness regarding treatment options for a rare disease in communities where there is traditionally resistance to the side effects of that treatment.

    Allow me to summarize what I think is going on here:

    Cushing’s disease is challenging to diagnose, many patients must visit multiple clinics before receiving an accurate diagnosis, and the disease remains largely underdiagnosed.
    Pro-life physicians may choose not to prescribe Korlym because of side-effects relating to pregnancy termination, restricting treatment options for patients in conservative districts.
    To overcome barriers to patients receiving the most possible options for treatment, Corcept provides compensation to physicians for legal, professional engagements to discuss their experience with Korlym administration in Cushing’s patients.
    As an addendum, Relacorilant, Korlym’s successor, is safer, more tolerable, and does not cause pregnancy termination.

    Off-label Korlym administration
    Throughout the report, the author insinuates that Corcept is promoting off-label usage.

    Off-label drug usage falls into an ethically challenging gray area. In some instances, off-label drug usage has significantly expanded treatment options for patients. For example, off-label avastin usage provides an effective treatment option for patients with age-related macular degeneration (AMD) that cannot afford the gold-standard Lucentis. Both drugs are marketed by Genentech. Avastin is orders of magnitude cheaper but is approved for use in cancer, not AMD.

    That being said, one of the reasons that the FDA exists is to prevent large corporations from taking advantage of patients with serious diseases. There are a few things that I think about in this case. Firstly, has Corcept actually promoted the off-label use of Korlym? The investor should consider this a possible risk, but at this point, there is next-to-no evidence to support this claim. The author needed to dig deeper than producing circumstantial evidence from one physician in Orlando. Secondly, has patient harm resulted from the off-label use of Korlym? Finally, due to the possible underdiagnoses of Cushing’s disease, does off-label usage expand a treatment option for underserved patients?

    Off-label usage is further complicated by Korlym’s secret double life as the abortion pill. Naturally, access to mifepristone – Korlym or otherwise – is controlled to prevent back-alley access to mifepristone.

    The bottom-line facts:

    Over 90% of Korlym prescriptions occur within the FDA-approved label
    In light of the potential risks, the FDA chose not to mandate a risk management assessment for off-label usage of Korlym
    I have seen no evidence that Corcept is promoting off-label prescription, illegally or otherwise.
    “The expectation for a peer-reviewed medical journal article is that an investigator’s research is conducted independently from consultations with a drug’s manufacturer”
    The author shows an email chain where Corcept encouraged the development of white paper guidelines in collaboration with physicians.

    This claim comes out of left-field and misleads the reader. Consider the COI policy of the New England Journal of Medicine, one of the top medical journals.

    The Journal’s policies were last revised in 1996.6 With regard to Original Articles and Special Articles, we will continue to follow the policy that was restated at that time. In such articles, we disclose the sponsorship of the studies and relevant financial information about the authors. During the editorial process, we ask authors for details of their financial relationships with biomedical companies, such as consulting fees, service on advisory boards, ownership of equity (or options thereon), patent royalties, honorariums for lectures, fees for expert testimony, and research grants. In a statement in such articles, we report all relevant financial relationships; if an author has reported no relevant financial relationships, there is no statement. We apply the same policy to Sounding Board articles, Case Records, and Perspectives. Our purpose in publishing financial-disclosure statements is to inform readers of the existence of financial relationships that, in our judgment, are pertinent to the article, and to affirm that we had access to this information during our deliberations.”

    Investigators consult with a drug’s manufacture all the time. The expectation is that these conflicts be disclosed in the article. I don’t agree with this statement by the author.

    Some final thoughts:
    SIRF maintains its status as a non-profit dedicated to investigative journalism, and author Roddy Boyd has denied financial COIs relating to the article.

    However, it is worth noting that someone made a lot of money placing trades before the article was published.

    https://pbs.twimg.com/media/Dx3lsB_WwAA-p6L.jpg:large

    Originally published by @gary_weiss on Twitter.

    Finally, the article neglects any real mention of Corcept’s research and development activities, which makes this report egregiously one-sided.

    Cortisol is one of the most well-known hormones and is involved in a large range of biological activities. In addition to developing Relacorilant in Cushing’s, Corcept is advancing compounds in clinical trials for multiple indications in cancer (including ovarian and prostate cancer), NASH, and mental health. Corcept has more partnerships with independent investigators than I have ever seen in a company their size. According to Pitchbook, the last time the company has raised outside money was in 2012, meaning that all of these programs have been supported by the high price of Korlym.

    Tying everything back to Corcept’s valuation, I think that the market reaction was overdone. The reasonable investor will be critical and investigate any claims about their investment, positive or negative. In this case, I ask myself:

    Has Corcept done anything illegal that risks incurring substantive legal action?
    Is any of the new information in the article likely to affect Corcept’s ongoing business operations?
    In my opinion, this report will blow over, and Corcept has again become undervalued. I used this opportunity to buy back shares that I sold last month after the new Korlym patent was issued.

  33. Theodore,
    I’ve written bluntly about the limits of FAERS as a data reporting system (see this article on Acadia Pharmaceuticals, specifically the paragraph about 1/2 way down that starts with: “These adverse event reports aren’t considered as conclusive….”) and I made extensive effort to address that. Put bluntly, FAERS reports are simply rough data that with some investigation can illuminate a trend.

    And, after the data is cleaned up, it’s evident there is a trend here.

    To start, I eliminated all instances where a patient who died while on Korlym but where the circumstances of death suggested that the drug had nothing to do it. For example, an event where the person on Korlym died after a car accident/complications from a fall/had a previous cancer diagnosis.

    I was helped in this analysis by speaking to pituitary specialists, as well as obtaining the longform FAERS reports on deaths that couldn’t readily be dismissed. Again, while these aren’t reports of an autopsy or even proper medical files — case histories can be spotty and background information can be limited — many of them do provide valuable context and data, such as dosage, circumstances of death, basic health datapoints, prominent side-effects, initial diagnosis and duration of Korlym use.

    What remained were 103 people that were on Korlym (and yes, often with other drugs) when they died, where the circumstances of death don’t immediately rule out their reaction to the course of treatment.

    What’s that mean? A few dozen of these deaths occurred shortly after increasing Korlym dosage strength. Few would conclude that a cause of death can be determined based on that alone, but as a data point, it can’t be readily discarded either.

    Finally, as an added check, I looked at the rate of growth of (noteworthy) death reports versus the rate of sales growth. Why? As a drug gains commercial acceptance, its adverse events will naturally increase; if over a two-year period sales increase 35% and death reports increase by 10%, that’s a (rough) indication that medical professionals aren’t observing a lot of morbidity connected to the drug.

    For Korlym, that ratio was sharply skewed in the wrong direction.

    Finally, I outlined these findings to the company, and the CFO said every last death, when investigated, had nothing to do with the medication.

    I think it’s a little more complex than that.

  34. See what happened to ACAD stock. When the article was published, the stock price was under 17 and yesterday it closed at 22.74. Those who read the article and exited the stock because of fear lost heavily.

  35. Thanks Roddy

    With all due respect, your own response pretty much confirms that this data cannot be relied upon. Data trends, statistics etc can be compiled and organized in any number of ways, depending on the desired outcome of the individual producing it. I feel you should have included your disclaimer regarding the pitfalls in FAERS reporting in the CORT article, and not assume someone would have seen it if they happened to read the ACADIA one.

  36. Theordore,

    I have no requirement to repeatedly post the same disclaimer in every article in which FAERS data is mentioned, and I’d posted it several times prior to the Acadia article as well, but I’ll do you a favor — I’m going to add it to this article, so that what I’d replied to you previously is crystal clear for all to read.

    Now it’s my turn to be baffled: You made some fairly strong declarations about the integrity of my work yet everything you’ve written demonstrates that you have never sought to understand FAERS data and the importance of its role in monitoring drug safety and efficacy.

  37. Thanks Roddy

    First – I’m not baffled. But I do find it odd that you don’t think it prudent to put the disclaimer in this article just because you posted it elsewhere. You need not do me any favors, just do what you feel is right, which apparently is what you’ve done by adding it to this article – and I applaud you. How you came to such a conclusion regarding anything I’ve sought or not sought to understand…well…wait, I take it back, that IS baffling. The only thing I can say at this point, and in response to this most recent reply, is that it comes off very defensive – and I believe you realize you should have included your earlier omission, but instead of owning it, you respond with a somewhat sarcastic remark that you’re doing it as a favor to me? ok 🙂

  38. Theodore,

    In retrospect, I should have put it the brief aside about how SIRF uses FAERS data, as well as its limitations, that had been run regularly since mid-2014. Assuming that it was now broadly understood among readers was indeed a mistake, and while not fatal per se, is an oversight nonetheless. Please note that we have addressed it at the place it’s first mentioned. Nor will this mistake be made again

    On a personal level, please accept my apology for not including it and then, when you noted it, not dealing with it in due-haste. Given the unusually personal tone of criticism directed at me and my family over this article by numerous commenters, I clearly failed to respond to your valid concerns; instead, looking at my comments, I acted defensively. Not a good look, frankly, and unprofessional of me.

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