FDA Declines to Approve Relacorilant for Hypertension Linked to Hypercortisolism

Posted on January 6, 2026 by MaryO

Key takeaways:

  • The FDA issued a complete response letter for relacorilant to treat hypertension tied to hypercortisolism.
  • The investigational drug induced BP reductions for adults with hypertension in the phase 3 GRACE trial.

The FDA has issued a complete response letter for an oral selective glucocorticoid receptor antagonist under investigation for the treatment of hypertension secondary to hypercortisolism, according to an industry press release.

Corcept Therapeutics announced the FDA issued a complete response letter for relacorilant (Corcept Therapeutics). The drug is under investigation for the treatment of endogenous hypercortisolism, ovarian cancer and other disorders, according to the company.

As Healio previously reported, the phase 3 GRACE trial enrolled 152 adults with Cushing’s syndrome plus hypertension, hyperglycemia or both conditions. Participants received relacorilant for 22 weeks during an open-label phase. At 22 weeks, adults who met criteria for hypertension or hyperglycemia control entered a withdrawal phase where they were randomly assigned, 1:1, to continue relacorilant or switch to placebo for 12 weeks.

In the GRACE trial, adults with hypertension had a 7.9 mm Hg decrease in systolic blood pressure and a 5.1 mm Hg decline in diastolic BP at 22 weeks. During the randomized withdrawal phase, adults who remained on relacorilant had no change in systolic and diastolic BP, whereas those receiving placebo had a BP increase from the start of the phase to week 12.

In a press release from Corcept Therapeutics from 2024, the company announced results from the phase 3 GRADIENT trial, a randomized, double-blind, placebo-controlled trial where adults with Cushing’s syndrome caused by an adrenal adenoma or adrenal hyperplasia were randomly assigned, 1:1, to relacorilant or placebo for 22 weeks. According to the press release, the relacorilant group had a 6.6 mm Hg decline in mean systolic BP compared with baseline at 22 weeks. However, there was no significant difference in mean systolic BP change between the relacorilant and placebo groups.

As Healio previously reported, relacorilant was also assessed in a long-term extension study that enrolled adults who completed the GRACE and GRADIENT trials as well as a phase 2 hypercortisolism study. In that trial, relacorilant conferred a 10 mm Hg drop in 24-hour ambulatory systolic BP and a 7.3 mm Hg reduction in 24-hour ambulatory diastolic BP at 24 months.

In the company’s press release announcing receipt of the complete response letter, Corcept Therapeutics said the FDA acknowledged that the GRACE trial met its primary endpoint and that the GRADIENT trial provided “confirmatory evidence.” However, the FDA said it did not view relacorilant offered “a favorable benefit-risk assessment” without more data of its effectiveness, according to the press release.

“We are surprised and disappointed by this outcome,” Joseph K. Belanoff, MD, CEO of Corcept Therapeutics, said in a press release. “Our commitment to patients suffering from the effects of hypercortisolism is unwavering. I am confident we will find a way to get relacorilant to the patients it could help. We will meet with the FDA as soon as possible to discuss the best path forward.”

https://www.healio.com/news/endocrinology/20251231/fda-declines-to-approve-relacorilant-for-hypertension-linked-to-hypercortisolism?utm_source=selligent&utm_medium=email&utm_campaign=20251231ENDO&utm_content=20251231ENDO

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First Oral Therapy for Rare Adrenal Gland Tumors Gets Green Light From FDA

Posted on May 17, 2025 by MaryO
FDA approval for Welireg.

The FDA has expanded the approval of belzutifanopens in a new tab or window (Welireg) to include certain types of pheochromocytoma or paraganglioma (PPGL) in adults and children.

The action establishes belzutifan as the only approved oral therapy for PPGL. The approval stipulates use in adults and children 12 years or older with locally advanced, unresectable, or metastatic PPGL.

Support for the approval came from the LITESPARK-015opens in a new tab or window multi-cohort trial. Cohort A1 involved 72 patients with locally advanced or metastatic PPGL not amenable to surgery or curative treatment. Patients with concomitant hypertension adequately managed with blood pressure medication were required to have stable therapy for at least 2 weeks prior to enrollment.

The primary outcome was objective response rate (ORR). Secondary outcomes included duration of response (DOR) and number of patients with at least a 50% dose reduction for one or more antihypertensive medications for at least 6 months.

The results showed an ORR of 26% and a median DOR of 20.4 months. Additionally, 19 of 60 patients on baseline antihypertensive medications met the prespecified dose-reduction target.

Adverse reactions occurring in ≥25% of patients included anemia; fatigue; musculoskeletal pain; increased liver enzymes, calcium, potassium, and alkaline phosphatase; decreased lymphocytes and leukocytes; dyspnea; headache; dizziness; and nausea.

PPGLs comprise a group of rare neuroendocrine tumorsopens in a new tab or window that have an incidence of approximately 0.57 per 100,000 person-years. The tumors occur in 0.1% t0 0.6% of patients with hypertension and account for about 5% of adrenal incidentalomas.

A hypoxia-inducible factor-2α inhibitor, belzutifan previously received approval for advanced renal cell carcinomaopens in a new tab or window and certain subtypes of von Hippel-Lindau diseaseopens in a new tab or window.

Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined MedPage Today in 2007. Follow 

From https://www.medpagetoday.com/hematologyoncology/othercancers/115582

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FDA Approval for Endogenous Cushing’s Syndrome Drug Recorlev

Posted on January 2, 2022 by MaryO

Ahead of its New Year’s Day decision deadline at the FDA, Xeris Biopharma has snagged an approval for Recorlev, a drug formerly known as levoketoconazole.

Based on results from phase 3 studies called SONICS and LOGICS, the FDA approved the drug for adults with Cushing’s syndrome. Xeris picked up Recorlev earlier this year in its acquisition of rare disease biotech Strongbridge Biopharma. It’s planning to launch in the first quarter of 2022.

Recorlev’s approval covers the treatment of endogenous hypercortisolemia in adults with Cushing’s syndrome who aren’t eligible for surgery or haven’t responded to surgery.

Endogenous Cushing’s disease is caused by a benign tumor in the pituitary gland that prompts the body to produce elevated levels of cortisol, which over time triggers a range of devastating physical and emotional symptoms for patients.

 

In the SONICS study, the drug significantly cut and normalized mean urinary free cortisol concentrations without a dose increase, according to the company. The LOGICS trial confirmed the drug’s efficacy and safety, Xeris says.

Cushion’s is a potentially fatal endocrine disease, and patients often experience years of symptoms before an accurate diagnosis, the company says. After a diagnosis, they’re presented with limited effective treatment options.

Following the approval, the company’s “experienced endocrinology-focused commercial organization can begin rapidly working to help address the needs of Cushing’s syndrome patients in the U.S. who are treated with prescription therapy,” Xeris CEO Paul R. Edick said in a statement.

Aside from its forthcoming Recorlev launch, Xeris markets Gvoke for severe hypoglycemia and Keveyis for primary periodic paralysis.

Back in October, the company partnered up with Merck to help reformulate some of the New Jersey pharma giant’s monoclonal antibody drugs.

From https://www.fiercepharma.com/pharma/xeris-biopharma-scores-fda-approval-for-endogenous-cushing-s-syndrome-drug-recorlev

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FDA Approves High-resolution MRI, Better at Spotting Pituitary Tumors in Cushing’s Patients

Posted on November 7, 2018 by MaryO

The U.S. Food and Drug Administration has approved the clinical use of a magnetic resonance imaging (MRI) scanner — the ultra-high-field 7T Terra MRI — with unprecedented resolution that allows for more reliable images of the brain.

The approach recently allowed the precise localization of a small tumor in the pituitary gland, which standard MRI had failed to spot, in a patient with Cushing’s disease.

So far, only one scanner of this kind exists in the U.S.. It was installed in February 2017 at the Mark and Mary Stevens Neuroimaging and Informatics Institute (INI) of the Keck School of Medicine, University of Southern California (USC).

The new scanner has an increased magnetic field strength of 7 Tesla, which is more than four times that of conventional MRI. This property greatly improves the instrument’s signal-to-noise ratio, dramatically increasing the spatial resolution and contrast of its images so that scientists can visualize the human living brain in high-definition and with unprecedented detail.

The 7T Terra is ideal for high-resolution neuroimaging, exploration of neurodegenerative diseases such as Alzheimer’s and Parkinson’s, and diagnosis and treatment of other brain diseases, a USC news story by Zara Greenbaum states.

Earlier this year, a report described the case of women with Cushing’s disease with a pituitary adenoma (slow-growing, benign tumor in the pituitary gland) that was possible to localize only with the new 7T MRI.

Based on laboratory analysis that revealed high levels of adrenocorticotropic hormone(ACTH) and cortisol, the doctors suspected a pituitary adenoma and recommended the patient for surgery. However, they ignored the precise location of the tumor, which failed to be detected by standard MRI scanners (1T and 3T).

    Two hours before surgery, the woman underwent a 7T MRI scan which finally identified with high precision the location of the adenoma, a very small tumor of 8 mm on the right side of the pituitary gland.

    “The 7T may save patients an invasive procedure. It also makes it easier for neurosurgeons to selectively remove a tumor without damaging surrounding areas,” said Gabriel Zada, MD, associate professor of neurological surgery at the Keck School.

    Since its arrival, the device has supported exploratory research into both healthy and diseased brains.

    Now the scanner’s advanced imaging technology can be used to help with diagnosis, treatment and monitoring of patients with neurological diseases, including Cushing’s disease.

    “This device, which has already made its mark as a powerful tool to advance research in the neurosciences, is now accessible to clinical populations in addition to researchers,” said Arthur W. Toga, PhD, provost professor and chair at the Keck School and director of the USC Stevens INI.

    “Clinicians across the university and beyond can now leverage all the benefits of increased spatial resolution to serve patients in need,” he said.

    Adapted from https://cushingsdiseasenews.com/2018/11/06/fda-oks-high-resolution-mri-better-spotting-pituitary-tumor-cushings/

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    [Pseudo-Cushing’s] Michigan woman nearly dies after herbal supplement found to be laced with steroids

    Posted on July 28, 2017 by MaryO

    MADISON HEIGHTS, Mich. (WXYZ) – Since 2004, the U.S. Food and Drug Administration has received more than 26,000 reports of adverse events and complaints about dietary supplements.

    Jody Higgins of Madison Heights, Michigan made one of those complaints to the FDA, after she says she found out the herbs she had been taking were making her seriously ill.

    “I really thought I was going to die I was getting so sick,” Higgins said.

    Back in 2015, Higgins says her legs started hurting.  She says she didn’t have great health insurance, and she was hoping for a more holistic approach, so a friend referred her to Far East Ginseng Herbs and Tea in nearby Sterling Heights.

    “They suggested that I take something that was called Linsen Double Caulis. I had never heard of it before, and it appeared to have all herbs on the label,” Higgins said.

    Higgins says for a while, she felt better, and when she stopped taking the Linsen Double Caulis, the leg pain returned. So, she says she kept taking it for nearly a year, even though she started noticing strange symptoms.

    “Within four months I had gained 80 pounds,” she said.

    She suddenly had facial hair growth, severe facial swelling, extremely swollen ankles, and had dark purple stretch marks all over her body.

    “I wasn’t recognizable,” said Higgins.  “I couldn’t stand for longer than 2 minutes. I couldn’t cook. I couldn’t wash my clothing. I could barely get in the shower.”

    After visiting several doctors, Higgins was eventually referred to University of Michigan Endocrinologist Dr. Ariel Barkan.

    “The minute that I said I had been taking a Chinese herbal remedy, he said ‘you’ve been poisoned. I know it.’ Those were his exact words,” said Higgins.

    “Her situation was pretty shaky,” Barkan said.

    Barkan sent the Linsin Double Caulis herbal supplement to the Mayo Clinic for testing.

    “They were loaded with Dexamethasone … [which] is a medication.  It’s a synthetic steroid, very potent, very long acting, and if we take it for quite some time, we develop what is called Cushing Syndrome,” said Dr. Barkan.

    Higgins was diagnosed with Cushing Syndrome, and Barkan says she could have died if she hadn’t sought help.

    “The mortality for untreated Cushing Syndrome is 50% within 5 years,” said Barkan.  “ … immunity is completely suppressed. And when you don’t have immunity, the first virus, the first germ may cause [a] fatal infection and you will die.”

    Higgins says once she stopped taking the Linsen Double Caulis, the facial hair went away, but she’s still struggling with her weight. Barkan says her health should improve, although it will take time.

    Both doctor and patient say they have contacted the FDA about this, and they each have a warning about taking herbal supplements.

    “Please just be very cautious,” Higgins said.

    “Don’t touch it. Don’t touch it, you’re playing Russian roulette,” said Barkan.

    Jody Higgins says she met with an investigator from the FDA’s criminal division.

    An FDA spokesperson would only say that they do not discuss possible or ongoing investigations.

    The lawyer for the store where Higgins says she purchased the supplement told us the owners will not be commenting on, but the owner did say they no longer sell this product.

    From http://www.fox4now.com/news/national/madison-heights-woman-herbal-supplement-caused-life-threatening-illness

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