Corcept Therapeutics Announces Allowance of Additional Patent Covering the Use of Korlym to Treat Patients With Cushing’s Syndrome

MENLO PARK, Calif., Aug. 28, 2019 (GLOBE NEWSWIRE) — Corcept Therapeutics Incorporated (NASDAQ: CORT) announced today that the United States Patent and Trademark Office has issued a Notice of Allowance for a patent covering the administration of Korlym® with food.  The patent will expire in November 2032.

“This patent covers an important finding of our research – that for optimal effect, Korlym must be taken with food,” said Joseph K. Belanoff, MD, Corcept’s Chief Executive Officer. “Korlym’s label instructs doctors that ‘Korlym must always be taken with a meal.’”

Upon issuance, Corcept plans to list the patent, entitled “Optimizing Mifepristone Absorption” (U.S. Pat. App. 13/677,465), in the U.S. Food and Drug Administration’s Approved Drug Products with Therapeutic Equivalence Evaluations (the “Orange Book”).  Korlym is currently protected by ten patents listed in the Orange Book.

Hypercortisolism

Hypercortisolism, often referred to as Cushing’s syndrome, is caused by excessive activity of the hormone cortisol. Endogenous Cushing’s syndrome is an orphan disease that most often affects adults aged 20-50. In the United States, an estimated 20,000 patients have Cushing’s syndrome, with about 3,000 new patients diagnosed each year. Symptoms vary, but most people with Cushing’s syndrome experience one or more of the following manifestations: high blood sugar, diabetes, high blood pressure, upper-body obesity, rounded face, increased fat around the neck, thinning arms and legs, severe fatigue and weak muscles. Irritability, anxiety, cognitive disturbances and depression are also common. Hypercortisolism can affect every organ system in the body and can be lethal if not treated effectively.

About Corcept Therapeutics Incorporated

Corcept is a commercial-stage company engaged in the discovery and development of drugs that treat severe metabolic, oncologic and psychiatric disorders by modulating the effects of the stress hormone cortisol.  Korlym® (mifepristone) was the first treatment approved by the U.S. Food and Drug Administration for patients with Cushing’s syndrome.  Corcept has discovered a large portfolio of proprietary compounds, including relacorilant, exicorilant and miricorilant, that selectively modulate the effects of cortisol but not progesterone. Corcept owns extensive United States and foreign intellectual property covering the composition of its selective cortisol modulators and the use of cortisol modulators, including mifepristone, to treat a variety of serious disorders.

Forward-Looking Statements

Statements in this press release, other than statements of historical fact, are forward-looking statements, which are based on Corcept’s current plans and expectations and are subject to risks and uncertainties that might cause actual results to differ materially from those such statements express or imply. These risks and uncertainties include, but are not limited to, Corcept’s ability to generate sufficient revenue to fund its commercial operations and development programs; the availability of competing treatments, including generic versions of Korlym; Corcept’s ability to obtain acceptable prices or adequate insurance coverage and reimbursement for Korlym; and risks related to the development of Corcept’s product candidates, including regulatory approvals, mandates, oversight and other requirements. These and other risks are set forth in Corcept’s SEC filings, which are available at Corcept’s website and the SEC’s website. In this press release, forward-looking statements include those concerning Corcept’s plans to list the patent “Optimizing Mifepristone Absorption” in the Orange Book; Korlym’s current protection by ten patents listed in the Orange Book; and the scope and protective power of Corcept’s intellectual property. Corcept disclaims any intention or duty to update forward-looking statements made in this press release.

CONTACT:
Christopher S. James, MD
Director, Investor Relations
Corcept Therapeutics
650-684-8725
cjames@corcept.com
www.corcept.com

Relacorilant Effectively Manages Cortisol Effects in Cushing’s Patients

Relacorilant, an investigational therapy developed by Corcept Therapeutics, may effectively manage the effects of excess cortisol in patients with Cushing’s syndrome, interim data from an ongoing Phase 2 trial show.

In particular, the treatment significantly improved sugar tolerance and the levels of osteocalcin, a bone growth biomarker  commonly suppressed by excess cortisol.

Corcept announced in a press release that the trial (NCT02804750) has completed patient enrollment. Results from the first patients will be presented during the upcoming 27th American Association of Clinical Endocrinologists (AACE) annual meeting, May 16-20 in Boston. Full data is expected by the third quarter of 2018.

Relacorilant, also known as CORT125134, was designed to prevent the effects of excess cortisol by blocking one of its receptors, the glucocorticoid receptor.

In a Phase 1 trial with healthy volunteers, multiple doses of relacorilant had a similar effect as Korlym (mifepristone) — an approved medicine for Cushing’s patients — without its known side effects.

In addition to the early efficacy data, the study showed that the treatment was generally safe and well-tolerated by the patients, with adverse events reportedly mild in severity.

These findings supported the launch of the Phase 2 trial in patients with Cushing’s syndrome. In the trial, roughly 30 patients are receiving escalating doses of relacorilant for a total of 12 weeks.

Patients were divided into two groups. The first group, which includes 17 patients, receives the lowest dose — 100 mg/day of relacorilant for four weeks, followed by 150 mg/day for four weeks, and then 200 mg/day for the last four weeks. The second group, called the high-dose cohort, is treated with a similar regimen but with a starting dose of 250 mg/day and a final dose of 350 mg/day.

Patients in the low-dose group had a significant improvement in their glucose tolerance and a 60% increase in blood osteocalcin.

In addition, the treatment reduced the blood pressure in 45% of patients with uncontrolled high blood pressure from cortisol excess. Importantly, the results after 12 weeks of relacorilant were similar to those seen after six months of Korlym treatment.

Safety data continues to show a positive profile, with no evidence of serious adverse effects and no affinity toward the progesterone receptor, which is a major drawback of Korlym.

“Relacorilant’s clinical results are striking because the doses these patients received were the study’s lowest. We did not expect patients to experience any meaningful clinical benefit, but they clearly did,” Robert S. Fishman, MD, chief medical officer of Corcept, said in the release. “We look forward to presenting data from these low-dose patients at the AACE meeting next week. With the trial’s final, high-dose cohort fully enrolled, we will have final data in the third quarter.”

Supported by these preliminary data, Corcept has accelerated the preparations for a Phase 3 trial on relacorilant in Cushing’s syndrome patients.

Korlym: How an abortion pill turned out to be a treatment for a rare disease

Even though the $550 yellow pills sold as Korlym have a controversial origin as the abortion pill, Leslie Edwin said they “gave me life.”

The 40-year-old Georgia resident lives with Cushing’s syndrome, a potentially deadly condition that causes high levels of the hormone cortisol to wreak havoc on a body. When first diagnosed, she said, she gained about 100 pounds, her blood sugars were “out of control,” and she suffered acne, the inability to sleep and constant anxiety.

“I wouldn’t leave the house,” Edwin said of her first bout with the condition. “I quit my job after a certain point. I just couldn’t keep being in front of people.”

That’s when Edwin endured surgeries, including one to remove her pituitary gland. She went into remission, but then, in 2016, her weight shot up 30 pounds and the anxious feelings returned. Her doctors prescribed Korlym.

The drug’s active ingredient is mifepristone, once called RU-486 and better known as the abortion pill because it causes a miscarriage when taken early in a pregnancy. Nearly two decades ago, Danco Laboratories won approval to market Mifeprex in the United States as the abortion drug, with tight restrictions on use. Corcept Therapeutics, a Silicon Valley-based drug company, began marketing Korlym six years ago as a specialty drug for about 10,000 rare-disease patients such as Edwin.

The difference in price between Korlym and Mifeprex is striking, even though the ingredients are the same: One 200-milligram pill to prompt an abortion costs about $80. In contrast, a 300-milligram pill prescribed for Cushing’s runs about $550 before discounts. (Patients wanting an abortion take only one pill. People with Cushing’s often take up to three pills a day for months or years.)

Joseph Belanoff, chief executive of the drug’s maker, Corcept, said Korlym’s average cost per patient is $180,000 annually and concedes that “we have an expensive drug. There’s no getting around that.” But, he said, he believes Corcept has a “social contract” to take care of patients and pledged that any patient who is prescribed Korlym will get it regardless of insurance coverage or costs.

The story of Korlym highlights how America’s drug development system can turn an old drug into a new one that treats relatively few — but often very desperate — patients.

When the Food and Drug Administration approved Korlym in 2012, it was designated as an orphan drug, giving Corcept seven years of market exclusivity as well as other economic incentives. Congress approved orphan drug incentives to encourage the development of medicines for rare diseases that affect fewer than 200,000 patients. Since the drug’s approval, Korlym’s price has risen about 150 percent, and last year the company’s revenue nearly doubled to $159.2 million and it reported a net income of $129.1 million. (Korlym is the company’s only product, and it treats about 1,000 patients in the United States.)

Belanoff said the profits from Korlym pay for the company’s past spending on the drug’s research and development as well as its effort to create new drugs. The company recently reported an encouraging Phase 2 trial update on Korlym’s successor, relacorilant, a drug that could treat Cushing’s without the side effects for some women of endometrial thickening and vaginal bleeding that can occur with Korlym.

The company’s pipeline is also full of potential oncology drugs that hold the promise of using molecules to influence the cortisol receptors, with wide-ranging effects in the body. Korlym in combination with another drug is being tested for the treatment of metastatic triple-negative breast cancer, which tends to be more aggressive than other types of breast cancer. And relacorilant is in the very early stages of testing to treat castration-resistant prostate cancer.

While many of the second-generation drugs are not related to Korlym structurally, Korlym did “provide the funding. . . . If there had not been orphan-drug pricing and the [Orphan Drug] Act, you would have to look for a different way to develop those drugs,” Belanoff said.

Korlym came to market in 2012 with an average wholesale price of $223.20 per pill before discounts, according to the health-care technology firm Connecture. By December 2017, each pill had an average wholesale price of $549.60 before any discounts or rebates were negotiated for patients.

Teva Pharmaceutical Industries recently announced it had filed an application to produce a generic version of the drug. Teva declined to comment for this report.

A ‘pioneering substance’

Cushing’s syndrome happens when the body produces too much cortisol, which normally helps keep the cardiovascular system functioning well and allows the body to turn proteins, carbohydrates and fats into energy. But too much cortisol can be destructive. It can cause cognitive difficulties, depression, fatigue, high blood pressure, bone loss and, in some cases, Type 2 diabetes. Those affected by the syndrome can develop a fatty hump between their shoulders and a rounded face. Without treatment, patients can die of a variety of complications, including sepsis after the hormone compromises the immune system.

Mifepristone, the active ingredient in Korlym, helps Cushing’s patients by blocking the body’s ability to process cortisol. It induces an abortion by blocking another of the body’s receptors, for progesterone, which causes the uterine wall to break down and the pregnancy to end.

When the FDA approved Korlym for a specific set of Cushing’s patients, the agency required a “TERMINATION OF PREGNANCY” warning box at the top of the label.

Endocrinologist Constantine Stratakis, scientific director at the National Institute of Child Health and Human Development, who specializes in treating people with Cushing’s syndrome, calls mifepristone a “pioneering substance” because it “has a lot of crossover” to other receptors in the body.

That means the drug has a lot of potential uses. Belanoff and Alan Schatzberg, a Stanford University psychiatrist and scientist, co-founded Corcept in 1998 to explore whether mifepristone could help treat major depression. In 2002, Schatzberg said the drug “may be the equivalent of shock treatments in a pill.” But clinical trials were not successful.

Social contract

By 2007, Corcept had found another possibility and filed an application to see whether mifepristone might work for Cushing’s patients.

Developing the drug cost about $300 million, according to Belanoff, and involved long-term toxicology tests to ensure that patients could safely take high doses for months or years. Korlym is approved to treat Cushing’s patients who have failed to relieve their symptoms through surgery or do not qualify for surgery, so some patients expect to take it for the rest of their lives while others just a few months.

Most patients are covered by private insurance, Belanoff said, but Medicare and Medicaid pay for the drug as well. According to Medicare Part D data, 52 Korlym patients cost Medicare $2.6 million in 2013. Two years later, 115 beneficiaries filed claims of $11.4 million.

Edwin is on private insurance and describes herself as being in “a really high tax bracket,” yet she never paid more than $25 a month through Corcept’s patient assistance program . She stopped taking the drug last year after her Cushing’s symptoms retreated.

“Across the board, it would be very difficult to find any patient that pays the full price,” said Edwin, who volunteers as president of the nonprofit patient advocacy group Cushing’s Support and Research Foundation.

The small organization, which reported $50,000 in contributions and grants in 2015, notes on its website that Corcept as well as Novartis Oncology provide financial support to the organization. The group’s federal tax filing details that the majority of its expenses go to distributing a quarterly newsletter, contacting members and patients “to promote mission,” and referring patients to doctors.

Specialty drugs such as Korlym often have sky-high price tags and are often distributed through special pharmacy programs. Drug companies commonly work with insurers and patient assistance programs to lower the patient’s out-of-pocket costs.

But for Corcept, the effort to brand the drug as a Cushing’s medication was also important, Belanoff said: “We were starting with a notorious drug.”

“There is a real infrastructure in caring for these patients,” he said. “It is not just like getting your medicine at [a drug store] and figuring out what to do with it.”

Sherwin D’Souza, an internal medicine doctor at St. Luke’s Boise Medical Center in Idaho, prescribed Korlym for the first time last year to Vonda Huddleston, who was uninsured. D’Souza said he knew Corcept would provide financial assistance until Huddleston could get insurance to help pay for surgery to remove a tumor in her adrenal gland that is suspected of causing her high cortisol levels.

Huddleston, though, did not feel well on the drug and gained weight. D’Souza took her off Korlym and scheduled surgery. “I was sort of trying to buy time and treat her conditions,” D’Souza said. “It’s very expensive . . . but they do have a very good program for patients in need of the drug.”

Kaiser Health News

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

Cortisol Modulator Shows Early Signs of Safety, Efficacy in Healthy Volunteers

The glucocorticoid receptor antagonist CORT125134 is safe and has shown preliminary signs of efficacy in healthy volunteers participating in a Phase 1 trial, say researchers in England.

Their study, “Assessment of Safety, Tolerability, Pharmacokinetics, and Pharmacological Effect of Orally Administered CORT125134: An Adaptive, Double-Blind, Randomized, Placebo-Controlled Phase 1 Clinical Study,” appeared in the journal Clinical Pharmacology in Drug Development.”

Cortisol signaling is indirectly controlled by the glucocorticoid receptor (GR). When cortisol binds the GR, the receptor becomes activated and migrates to the nucleus, where it regulates the expression of many genes. This influences a myriad of processes, including inflammation, immune response and brain function.

CORT125134, also known as relacorilant, is being developed by Corcept Therapeutics of Menlo Park, California, for Cushing’s disease patients and others who may benefit from it. The drug is a GR antagonist, blocking the receptor’s activity.

In order to evaluate the safety and tolerability of CORT125134, and learn how it behaves in the body, Corcept researchers conduced a Phase 1 trial in healthy subjects.

The British study, conducted at the Quotient Clinical in Nottingham, included 81 adults who received a single ascending-dose of CORT125134 or placebo, and 48 subjects who received multiple-ascending doses of the drug versus placebo.

Single doses were tested in nine distinct groups. Six tested six different doses of CORT125134, one tested a 150 mg dose in subjects receiving a high-fat meal, and two groups included patients receiving prednisone (a well-known GR activator), prednisone plus Korlym (mifepristone), or prednisone plus CORT125134.

Korlym is a medicine approved for Cushing’s  patients with high blood sugar levels due to high cortisol in circulation. But the drug targets the progesterone receptor and is associated with side effects like pregnancy termination and irregular vaginal bleeding.

Multiple doses, given for up to 14 days, were tested in four additional cohorts. Researchers observed that CORT125134 was rapidly absorbed and eliminated, presenting a suitable profile for once-daily dosing.

Efficacy was determined by CORT125134’s ability to counteract the effects of prednisone. In addition, a single dose of 500 mg or multiple dosing with 250 mg had similar effects as those seen with 600 mg of Korlym — the therapeutic dose used for Cushing’s treatments.

Most common treatment-related adverse events reported in the single-ascending dose part of the study were nausea, vomiting and thirst; most were mild. In those given multiple-ascending doses, adverse events included mild musculoskeletal and connective tissue disorders, as well as gastrointestinal system disorders.

Multiple 500 mg doses exceeded the maximum tolerated dose, as it led to musculoskeletal symptoms that forced researchers to stop treatment.

“This first-in-human study has demonstrated that CORT125134 is well tolerated following single doses up to 500 mg and repeated doses up to 250 mg once daily for 14 days,” researchers wrote. “Pharmacological activity was confirmed following the administration of a single 500-mg dose and daily administration of 250 mg.”

Corcept is now enrolling participants into a Phase 2 open-label trial (NCT02804750) to evaluate CORT125134 in patients with Cushing’s syndrome. This trial is being conducted in the United States and Europe and will include 80 participants. Top-line results are expected in the first quarter of 2018.

From https://cushingsdiseasenews.com/2017/10/10/phase-1-data-demonstrates-efficacy-safety-of-cort125134-in-healthy-volunteers/

Corcept Therapeutics Announces Presentations on Mifepristone for the Treatment of Patients with Hypercortisolism

MENLO PARK, CA — (Marketwired) — 05/04/17 — Corcept Therapeutics Incorporated (NASDAQ: CORT), a pharmaceutical company engaged in the discovery, development and commercialization of drugs that treat severe metabolic, oncologic and psychiatric disorders by modulating the effects of cortisol, today announced that presentations about hypercortisolism and mifepristone’s role in treating that disorder will be presented at the 26th Annual Congress of the American Association of Clinical Endocrinologists (AACE) being held at the Austin Convention Center in Austin, Texas.

“There is growing awareness that even less severe degrees of hypercortisolism are harmful,” said Joseph K. Belanoff, M.D., Corcept’s Chief Executive Officer. “As a result, physicians are increasingly screening patients whose metabolic and cardiovascular symptoms have not responded to conventional therapy and finding cases of previously undetected Cushing’s syndrome.”

In addition to viewing the posters described below, AACE attendees may attend “Evolving Paradigms of Hypercortisolism,” a product theater talk by Ty Carroll, M.D. Corcept is a sponsor of the talk.

----------------------------------------------------------------------------
                            Thursday, May 4, 2017
----------------------------------------------------------------------------
             Poster #124
 Screening of Diabetic Patients Using
                U500
Insulin Uncovers a High Percentage of     Joseph W. Mathews, M.D., FACE
     Undiagnosed Hypercortisolism              James J. Smith, PhD
             Consistent
        with Cushing Syndrome
----------------------------------------------------------------------------
                    Friday, May 5, 2017, 12:45 - 1:30pm
                              Product Theater B
----------------------------------------------------------------------------
        Evolving Paradigms of
           Hypercortisolism                      Ty Carroll, M.D.
----------------------------------------------------------------------------
                             Friday, May 5, 2017
----------------------------------------------------------------------------
             Poster #131
      Medical Management of Mild
     Hypercortisolism and Primary
   Aldosteronism in a Patient with            Sandi-Jo Galati, M.D.
    ACTH-Independent Macronodular         Michele Lamerson, RN, MS, CPNP
             Hyperplasia
      Presenting with Resistant
            Hypertension
----------------------------------------------------------------------------
                                     Adriana G. Ioachimescu, M.D., PhD, FACE
             Poster #608                  Jonathan G. Ownby, M.D., FACE
   Improving Glycemic Control with       Nicole G. Greyshock, M.D., FACE
            Mifepristone                   Thomas C. Jones, M.D., FACE
in Cushing Syndrome Patients May Lead     Gary S. Wand, M.D., PhD, FACE
     to Significant Weight-loss                James J. Smith, PhD
----------------------------------------------------------------------------
             Poster #725
  Successful Medical Management with           Saima Farghani, M.D.
Mifepristone in a Patient with Occult     Michele Lamerson, RN, MS, CPNP
      Ectopic Cushing Syndrome
----------------------------------------------------------------------------
             Poster #836
  Mifepristone Therapy Significantly
              Improved
Insulin Resistance, Glycemic Control,     Jonathan G. Ownby, M.D., FACE
  and Weight Loss in a Patient with            James J. Smith, PhD
           Cushing Disease
 Previously Treated with Pasireotide
----------------------------------------------------------------------------
             Poster #839
  Mifepristone Reduced U500 Insulin
   Usage in a Patient with Cushing       Kimberley A. Bourne, M.D., FACE
  Disease and Normalized Concomitant           James J. Smith, PhD
 Fatty Liver Disease and Retinopathy
----------------------------------------------------------------------------

About Corcept Therapeutics Incorporated
Corcept is a pharmaceutical company engaged in the discovery, development and commercialization of drugs that treat severe metabolic, oncologic and psychiatric disorders by modulating the effects of cortisol. Korlym®, a first-generation cortisol modulator, is the company’s first FDA-approved medication. The company has a portfolio of proprietary compounds that modulate the effects of cortisol but not progesterone. Corcept owns extensive intellectual property covering the use of cortisol modulators, including mifepristone, in the treatment of a wide variety of serious disorders, including Cushing’s syndrome. It also holds composition of matter patents covering its selective cortisol modulators.

From http://news.sys-con.com/node/4073068

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