Korlym (mifepristone) / Corcept Therap - LARVOL DELTA

Differential Coregulator Recruitment by A Novel Glucocorticoid Receptor Modulator with Disease-Modulating Activities in Vivo (ENDO 2026) - "There is a great need for new drugs that effectively antagonize glucocorticoid receptor (GR) signaling, as the clinically approved drug mifepristone (RU-486) exhibits cross-reactivity for the progesterone receptor (PR)...Third, at 60 mg/kg/day CORT126775 effectively potentiated the antitumor activity of the chemotherapeutic drug paclitaxel in MiaPaCa-xenografted mice...RNA-sequencing analysis is currently ongoing to delineate gene-specific GR antagonistic effects of CORT126775 in the absence and presence of gelsolin. In conclusion, we present a novel selective GR modulator that induces a unique GR transcription complex and that exhibits robust antagonism in vitro and in clinically-relevant disease models in vivo."

Preclinical • Cardiovascular • Diabetes • Hypertension • Metabolic Disorders • Type 2 Diabetes Mellitus • GSN • KMT2C • MBD4 • MED1 • NCOA1 • NCOA4 • PGR • UBE3A

Differential Coregulator Recruitment by A Novel Glucocorticoid Receptor Modulator with Disease-Modulating Activities in Vivo (ENDO 2026) - "There is a great need for new drugs that effectively antagonize glucocorticoid receptor (GR) signaling, as the clinically approved drug mifepristone (RU-486) exhibits cross-reactivity for the progesterone receptor (PR)...Third, at 60 mg/kg/day CORT126775 effectively potentiated the antitumor activity of the chemotherapeutic drug paclitaxel in MiaPaCa-xenografted mice...RNA-sequencing analysis is currently ongoing to delineate gene-specific GR antagonistic effects of CORT126775 in the absence and presence of gelsolin. In conclusion, we present a novel selective GR modulator that induces a unique GR transcription complex and that exhibits robust antagonism in vitro and in clinically-relevant disease models in vivo."

Preclinical • Cardiovascular • Diabetes • Hypertension • Metabolic Disorders • Type 2 Diabetes Mellitus • GSN • KMT2C • MBD4 • MED1 • NCOA1 • NCOA4 • PGR • UBE3A

SI02-02 - From Symptoms to Solutions: The Patient Experience with Korlym® (mifepristone) Treatment (ENDO 2026) - "Please see the Important Safety Information, including Boxed Warning for Termination of Pregnancy, and the full Prescribing Information at the Product Theater. In addition to the esteemed panelists, we will have a Korlym patient join the discussion!"

Clinical

PT2-05: Product Theaters - From Symptoms to Solutions: The Patient Experience with Korlym® (mifepristone) Treatment (ADA 2026) - "Please see the Important Safety Information, including Boxed Warning for Termination of Pregnancy, and the full Prescribing Information at the Product Theater. (*) Continuing Education Credit Is Not Awarded for this Session."

Clinical • Metabolic Disorders

At ADA, Corcept also presented late-breaking data from its MOMENTUM trial, which screened 1,086 patients with resistant hypertension (as defined by the American Heart Association’s criteria) and found that 27.3 percent of them had hypercortisolism. (Businesswire) - "The prevalence of hypercortisolism was even higher in patients who had hemoglobin A1c (HbA1c) of 7.5 percent or higher and were taking 3 or more blood pressure medicines...32.6 percent in MOMENTUM."

Observational data • Cushing’s Disease

The CATALYST trial screened 1,057 patients with difficult-to-control type 2 diabetes (HbA1c of 7.5 – 11.5 percent despite receiving multiple glucose-lowering medications) and found that 24 percent had hypercortisolism (cortisol levels of greater than 1.8 μg/dL in the 1 mg dexamethasone suppression test (DST)). (Businesswire) - "Patients who received Korlym exhibited a clinically meaningful and statistically significant reduction in HbA1c (1.3 percent, p-value: <0.001)...The data presented at ADA described treatment outcomes in the 71 patients in CATALYST who were taking GLP-1 receptor agonists or the GLP-1/GIP agonist tirzepatide. In this group, patients who received Korlym exhibited numerically greater benefit than the overall study population with reductions in HbA1c (1.7 percent), body weight (6.1 kg), body mass index (2.0 kg/m2) and waist circumference (6.5 cm), compared to patients who received placebo (all nominal p-values less than 0.04)."

P4 data • Cushing’s Disease

Identification of breakpoint regions and single nucleotide variations of RHD hybrid alleles by long-read sequencing. (PubMed, Vox Sang) - "Three intronic SNVs can be used to accurately identify RHD*DIIIa-CEVS(4-7)-D."

Journal • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Cortisol's role in difficult-to-control type 2 diabetes: Insights from the CATALYST study-a plain language review. (PubMed, Curr Med Res Opin) - No abstract available

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Product Theater: From Symptoms to Solutions: The Patient Experience with Korlym® (mifepristone) Treatment Sponsored by Corcept (AACE 2026) - "Please see the Important Safety Information, including Boxed Warning for Termination of Pregnancy, and the full Prescribing Information at the Product Theater. In addition to the esteemed panelists, we will have a Korlym patient join the discussion!"

Clinical

Cyhalothrin induced neurotoxicity via disrupting NF-κB and L-glutamate signaling and functions in zebrafish (Danio rerio). (PubMed, Comp Biochem Physiol C Toxicol Pharmacol) - "Mechanism findings revealed that it regulated the gene expression levels of NF-κB (tnfa, il1b, map3k14a, nfkbiaa, nfkbiab and tnfrsf1a) and L-Glutamate signaling pathway (slc6a19a.2, slc1a5, si:ch1073-155 h21.2 and gls2a) to impair the GABA secretion. The results showed that cyhalothrin elicited neurotoxicity in the zebrafish embryo, and the possible mechanism is that it induced inflammation, which in turn disorder GABA secretion. It may be utilized for evaluating zebrafish health and neurological disease studies."

Journal • CNS Disorders • Inflammation • IL1B • SLC1A5 • TNFA • TNFRSF1A

Mifepristone, a glucocorticoid receptor antagonist, reduced HbA1c and body weight in difficult-to-control type 2 diabetes with hypercortisolism: the CATALYST prevalence and treatment trial (EASD 2025) - P4 | "The CATALYST study demonstrated that treating hypercortisolism with cortisol-directed therapy, specifically mifepristone, significantly reduced HbA1c, body weight, and waist circumference in individuals with uncontrolled T2D despite multiple glucose-lowering therapies. This study supports the need to consider evaluating and addressing hypercortisolism in this patient population."

Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Effects Of Relacorilant On Pituitary Tumor Volume In Patients With Cushing Disease: Results From The Phase 3 Grace Study (ENDO 2025) - P3 | "Previous case reports suggested that the pituitary tumor effects of relacorilant in patients with Cushing Disease (CD) are distinct from those of the FDA-approved GR antagonist mifepristone (Pivonello Front Endocrinol 2022)...In summary, pituitary tumor volume decreased or remained unchanged following treatment with relacorilant for the majority of patients with CD in the GRACE study. Relacorilant was also well-tolerated and led to significant improvements in HC-related signs and symptoms."

Clinical • Late-breaking abstract • P3 data • Cardiovascular • Cushing’s Disease • Diabetes • Endocrine Cancer • Hypertension • Oncology • Pituitary Gland Carcinoma • SSTR • SSTR2

Molecular Profiling of the Selective Glucocorticoid Receptor Modulators CORT118335 (Miricorilant) and CORT125385 With Lipid-Lowering Properties in the Liver (ENDO 2025) - "Mice were subsequently treated with vehicle, the GR agonist corticosterone (3 mg/kg/day), the GR antagonist mifepristone, CORT118335 or CORT125385 (all 60 mg/kg/day) for three days...GO-term analysis on gene subsets after applying molecular filters suggested that the lipid-lowering effects of SGRMs likely involve corticosterone-like upregulation and SGRM-specific downregulation of genes. We tentatively conclude that CORT118335- and CORT125385-induced GR modulation results in a unique transcriptional profile, thereby lowering hepatic lipid levels."

Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Inadequately Controlled Type 2 Diabetes and Hypercortisolism: Improved Glycemia With Mifepristone Treatment. (PubMed, Diabetes Care) - "In individuals with inadequately controlled T2D and hypercortisolism, cortisol-directed medical therapy with mifepristone reduced HbA1c, with a manageable tolerability profile."

Journal • Diabetes • Fatigue • Metabolic Disorders • Pain • Type 2 Diabetes Mellitus

CORCEPT THERAPEUTICS ANNOUNCES FIRST QUARTER FINANCIAL RESULTS AND PROVIDES CORPORATE UPDATE (Businesswire) - "Clinical Development:...Hypercortisolism (Cushing’s Syndrome) - (i) GRACE - Pivotal Phase 3 trial of relacorilant in 152 patients with all etiologies of hypercortisolism - Results presented at Endocrine Society (ENDO) annual meeting and Heart in Diabetes (HiD) conference in June 2024; (ii) GRADIENT - Randomized, double-blind, placebo-controlled, Phase 3 trial of relacorilant in 137 patients with hypercortisolism caused by adrenal gland pathology – Results will be presented at American Association of Clinical Endocrinology (AACE) annual meeting in May 2025...; (iii) CATALYST Part 2 - Randomized, double-blind, placebo-controlled study of Korlym in 136 patients with hypercortisolism - Results to be presented at the American Diabetes Association’s 85th Scientific Sessions (ADA) in June 2025; (iv) MOMENTUM - Enrollment continues in 1,000-patient trial examining the prevalence of hypercortisolism in patients with resistant hypertension - Results expected by year-end."

Clinical data • Cushing’s Disease

Study to Determine the Prevalence of Hypercortisolism in Patients With Type 2 Diabetes and Treatment With Korlym® (Mifepristone) (CATALYST) (clinicaltrials.gov) - P4 | N=1113 | Completed | Sponsor: Corcept Therapeutics | Recruiting ➔ Completed | Trial completion date: Jul 2024 ➔ Dec 2024 | Trial primary completion date: May 2024 ➔ Nov 2024

Trial completion • Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

A RARE CRANIOSYNOSTOSIS RESEMBLING CROUZON SYNDROME WITH VARIANTS INVOLVING THE INTERLEUKIN 11 RECEPTOR. (WRMC 2025) - "Genetic testing showed bi-allelic pathogenic variants in IL11RA (c.82C>T, p.Gln28*; c.1073-1G>C, splice acceptor). CS is one of the most common congenital craniofacial malformations with more genetic heterogeneity than previously thought. IL11RA-related CRSDA should be considered in patients with a Crouzon-like phenotype with or without CS. IL11RA is thought to play a role in restricting premature fusion of sutures by mediating osteoblast-osteoclast differentiation postnatally."

FGFR2 • FGFR3 • IL1R1 • STAT1 • TCF12 • TWIST1

Abraxane® With or Without Mifepristone for Advanced, Glucocorticoid Receptor-Positive, Triple-Negative Breast Cancer (clinicaltrials.gov) - P2 | N=29 | Active, not recruiting | Sponsor: University of Chicago | Trial completion date: Aug 2024 ➔ Aug 2026

Metastases • Trial completion date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

RESET-medication Glucocorticoid Receptor (GR) Blockade As Disease Modifying Treatment for Depression with Childhood Trauma (clinicaltrials.gov) - P2 | N=158 | Completed | Sponsor: Amsterdam UMC, location VUmc | Recruiting ➔ Completed | Trial completion date: Jun 2024 ➔ Nov 2024 | Trial primary completion date: Dec 2023 ➔ Aug 2024

Trial completion • Trial completion date • Trial primary completion date • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • CRP • IL6 • TNFA

REVERSE: Improving Treatment-resistant Post Traumatic Stress Disorder (PTSD) with Glucocorticoid Receptor (GR) Antagonism (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Christiaan Vinkers

New P2 trial • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

PSEN2 Mutations May Mimic Frontotemporal Dementia: Two New Case Reports and a Review. (PubMed, Biomedicines) - "Prominent behavioral and language dysfunction suggesting frontotemporal dementia (FTD) may be underestimated in the literature as a clinical picture in PSEN2 mutations. Thus, it may be reasonable to include PSEN2 in genetic panels when suspecting FTDL. PSEN2 mutations may cause striking WMH, arguably related to myelin disruption induced by amyloid accumulation."

Journal • Review • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration

Study protocol for a prospective, multicentre study of hypercortisolism in patients with difficult-to-control type 2 diabetes (CATALYST): prevalence and treatment with mifepristone. (PubMed, BMJ Open) - P4 | "In part 1, approximately 1000 participants with difficult-to-control T2D (haemoglobin A1c (HbA1c) 7.5%-11.5% despite multiple therapies) are screened with a 1 mg dexamethasone suppression test (DST)...Those requiring evaluation for elevated ACTH are referred for care outside the study; those with ACTH and DHEAS in the range may advance to part 2, a randomised, double-blind, placebo-controlled trial to evaluate the impact of treating hypercortisolism with the competitive glucocorticoid receptor antagonist mifepristone (Korlym®)...Findings will be presented at scientific meetings and published in peer-reviewed journals. NCT05772169."

Clinical protocol • Journal • Diabetes • Endocrine Cancer • Endocrine Disorders • Metabolic Disorders • Nephrology • Oncology • Type 2 Diabetes Mellitus

Rapid Clinical Improvements in a Patient with Difficult-to-Control Type 2 Diabetes by Addressing Underlying Hypercortisolism with Mifepristone (AACE 2024) - "Case(s) Description A 71-year-old man with long-standing (40+ years) difficult-to-control T2D (continuous glucose monitoring [CGM] time-in-range [TIR] 41%, HbA1c 8%, average glucose 196 mg/dL) despite receiving multiple antihyperglycemic drugs (including U500 insulin, metformin, and GLP1 agonists) also had multiple comorbidities, including resistant hypertension (on 7 antihypertensive medications) and morbid obesity (post gastric sleeve). His biochemical evaluation confirmed hypercortisolism with elevated serum cortisol (2.3 and 2.4 μg/dL) post-1-mg dexamethasone suppression test, and computed tomography imaging revealed a stable sub-centimeter adrenal adenoma...This case emphasizes the vital importance of promptly identifying and addressing hypercortisolism in patients with challenging metabolic derangements. Failure to do so resulted in a worsening clinical picture for this patient, which was ameliorated with the administration of mifepristone to address the underlying..."

Clinical • Cardiovascular • Diabetes • Genetic Disorders • Hypertension • Hypotension • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

INIA Stress and Chronic Alcohol Interactions: Glucocorticoid Antagonists in Heavy Drinkers (clinicaltrials.gov) - P1/2 | N=65 | Completed | Sponsor: Johns Hopkins University | Phase classification: P=N/A ➔ P1/2

Phase classification • Addiction (Opioid and Alcohol)

Rapid Clinical Improvements in a Patient with Difficult-to-Control Type 2 Diabetes by Addressing Underlying Hypercortisolism with Mifepristone (ENDO 2024) - "CASE PRESENTATION: A 71-year-old man with long-standing (40+ years) difficult-to-control T2D (continuous glucose monitoring [CGM] time-in-range [TIR] 41%, HbA1c 8%, average glucose 196 mg/dL) despite receiving multiple antihyperglycemic drugs (including U500 insulin, metformin, and GLP1 agonists) also had multiple comorbidities, including resistant hypertension (on 7 antihypertensive medications) and morbid obesity (post gastric sleeve). His biochemical evaluation confirmed hypercortisolism with elevated serum cortisol (2.3 and 2.4 μg/dL) post-1-mg dexamethasone suppression test, and computed tomography imaging revealed a stable sub-centimeter adrenal adenoma... This case presents a patient with difficult-to-control T2D and additional comorbidities that could not be effectively managed despite long-term, extensive medical interventions. This case emphasizes the vital importance of promptly identifying and addressing hypercortisolism in patients with challenging metabolic..."

Clinical • Cardiovascular • Diabetes • Genetic Disorders • Hypertension • Hypotension • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus