dazucorilant (CORT113176) / Corcept Therap - LARVOL DELTA

Corcept Phase 2 Study of Dazucorilant Demonstrates Two-Year Overall Survival Benefit in Patients with Amyotrophic Lateral Sclerosis (Businesswire) - "Although DAZALS did not meet its primary endpoint, at the end of the 24-week treatment period patients who received 300 mg of dazucorilant daily did exhibit improved overall survival (p-value: 0.02). Exploratory analyses show that this survival benefit has continued. In the two years following the start of treatment, patients who received 300 mg of dazucorilant experienced an 87 percent reduction in the risk of death compared to patients who received placebo and did not switch to 300 mg of dazucorilant in the extension phase (hazard ratio: 0.13; p-value: < 0.0001)....Between these groups, the reduction in risk of death in patients who received 300 mg of dazucorilant was 64 percent at one year (hazard ratio: 0.36; p-value: 0.02) and 61 percent at two years (hazard ratio: 0.39; p-value: 0.02)."

P2 data • Amyotrophic Lateral Sclerosis

Clinical Development (Corcept Therapeutics Press Release) - "'In addition, results from MONARCH, our Phase 2b trial in patients with metabolic dysfunction-associated steatohepatitis (MASH), are expected by the end of this year. We also plan to start a Phase 3 trial of dazucorilant in patients with ALS later this year.'"

New P3 trial • P2b data • Amyotrophic Lateral Sclerosis • Metabolic Dysfunction-Associated Steatohepatitis

DAZALS: Dazucorilant in Patients With Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P2 | N=279 | Recruiting | Sponsor: Corcept Therapeutics | Active, not recruiting ➔ Recruiting

Enrollment open • Amyotrophic Lateral Sclerosis • CNS Disorders • SOD1

Amyotrophic Lateral Sclerosis (ALS) (Businesswire) - "DAZALS - Exploratory analyses showed that patients who received dazucorilant 300 mg exhibited an 84 percent reduction in risk of death during the study’s first year compared to patients who received placebo (hazard ratio: 0.16, p-value: 0.0009). Phase 3 trial - Planned to begin by the middle of this year."

New P3 trial • P2 data • Amyotrophic Lateral Sclerosis

DAZALS: Dazucorilant in Patients With Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P2 | N=279 | Active, not recruiting | Sponsor: Corcept Therapeutics | Trial completion date: May 2027 ➔ Nov 2027 | Trial primary completion date: Oct 2024 ➔ Sep 2026

Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

Amyotrophic Lateral Sclerosis (ALS) (Businesswire) - "Phase 3 trial - Expected to begin by the middle of next year."

New P3 trial • Amyotrophic Lateral Sclerosis

Targeting microglial glucocorticoid receptors to mitigate Alzheimer's disease pathology (ECNP 2025) - "(2025) showed that treatment with dazucorilant (CORT113176), a selective GR modulator, improved both working and long-term spatial memory in J20 and 5xFAD mouse models of amyloid pathology [5]...We will evaluate how GR deletion in microglia impacts gene expression, synaptic function and plasticity, as well as phagocytic capacity. This foundational research will provide critical insight into how microglial GR signalling contributes to cognition and may reveal mechanisms through which ELS influences AD vulnerability."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Aβ42 • CD68 • CX3CR1

Impact of Itraconazole on the Pharmacokinetics and Safety of Dazucorilant in Healthy, Adult Participants (clinicaltrials.gov) - P1 | N=21 | Completed | Sponsor: Corcept Therapeutics | Active, not recruiting ➔ Completed | Trial completion date: Apr 2025 ➔ Aug 2024

Trial completion • Trial completion date

Corcept Presents Results from Phase 2 Study of Dazucorilant in Patients with Amyotrophic Lateral Sclerosis (ALS) at ENCALS 2025 Annual Meeting (Businesswire) - P2 | N=249 | DAZALS (NCT05407324) | Sponsor: Corcept Therapeutics | "Corcept Therapeutics Incorporated...presented results from its DAZALS study of dazucorilant in patients with ALS at the European Network to Cure ALS (ENCALS) 2025 annual meeting....Although DAZALS did not meet its primary endpoint, patient survival significantly improved. At week 24 of the study, no deaths had occurred in the 83 patients who received 300 mg of dazucorilant, while there were five deaths in the 82-patient placebo group (p-value of 0.02). An exploratory analysis conducted at the one-year mark shows the survival benefit has continued. Patients randomized to 300 mg of dazucorilant lived significantly longer than patients who received placebo and did not switch to 300 mg of dazucorilant in the extension study."

P2 data • Amyotrophic Lateral Sclerosis

CORCEPT THERAPEUTICS ANNOUNCES FIRST QUARTER FINANCIAL RESULTS AND PROVIDES CORPORATE UPDATE (Businesswire) - "Clinical Development:...(i) Amyotrophic Lateral Sclerosis (ALS):...DAZALS - Results to be presented at European Network to Cure ALS (ENCALS) annual meeting in June 2025...; (ii) Metabolic Dysfunction-Associated Steatohepatitis (MASH): MONARCH – Enrollment continues in randomized, double-blind, placebo-controlled, Phase 2b trial of miricorilant in patients with biopsy-confirmed or presumed MASH....'We look forward to building on these promising results in our MONARCH study. First results are expected by the end of next year'..."

P2 data • Amyotrophic Lateral Sclerosis • Metabolic Dysfunction-Associated Steatohepatitis

Effects of Hepatic Impairment on the Pharmacokinetics of Dazucorilant (clinicaltrials.gov) - P1 | N=19 | Completed | Sponsor: Corcept Therapeutics

New P1 trial • Hepatology

Impact of Itraconazole on the Pharmacokinetics and Safety of Dazucorilant in Healthy, Adult Participants (clinicaltrials.gov) - P1 | N=21 | Active, not recruiting | Sponsor: Corcept Therapeutics | Recruiting ➔ Active, not recruiting | Trial completion date: Jul 2024 ➔ Apr 2025

Enrollment closed • Trial completion date

Advancing Alzheimer's disease pharmacotherapy: efficacy of glucocorticoid modulation with dazucorilant (CORT113176) in preclinical mouse models. (PubMed, Br J Pharmacol) - "Dazucorilant exhibited sustained disease-modifying effects in two AD models. Given that this compound has demonstrated safety and tolerability in human subjects, our results provide pre-clinical support for conducting clinical trials to evaluate its potential in AD."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation • Mood Disorders • Psychiatry

Corcept Announces Results From Phase 2 Study of Dazucorilant in Patients With Amyotrophic Lateral Sclerosis (ALS) (Businesswire) - P2 | N=249 | DAZALS (NCT05407324) | Sponsor: Corcept Therapeutics | "Corcept Therapeutics Incorporated...announced results from the DAZALS study...evaluating two doses...of...dazucorilant in patients with ALS....DAZALS did not meet its primary endpoint, which was the change from baseline in the ALS Functional Rating Scale-Revised (ALSFRS-R) in patients who received dazucorilant compared to those who received placebo. Patients who received dazucorilant experienced substantially more gastrointestinal upset at the onset of treatment than those who received placebo. During the 24-week study, no deaths (0/83) were observed in the 300 mg arm, compared to 5 deaths (5/82) in the placebo group (p-value: 0.02). The open-label, long-term extension study will continue and overall survival will be assessed in March 2025 after all patients have had one year pass since the onset of treatment....Complete results from the DAZALS study will be presented at a medical conference next year."

P2 data • Amyotrophic Lateral Sclerosis

Traumatic stress-induced glucocorticoid signaling and rat behavior (Neuroscience 2024) - "All rats then immediately received infusion of either vehicle or CORT113176, a GR antagonist, and received additional doses for the two days following...The data indicate that infusions of GR antagonist tend to promote expression of fear related behaviors, even when administered several days prior to testing. These studies suggest that the glucocorticoid response to SPS may be required for appropriate processing of fear memories."

Preclinical • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry

Impact of Itraconazole on the Pharmacokinetics and Safety of Dazucorilant in Healthy, Adult Participants (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Corcept Therapeutics

New P1 trial

DAZALS: Dazucorilant in Patients With Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P2 | N=249 | Active, not recruiting | Sponsor: Corcept Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Amyotrophic Lateral Sclerosis • CNS Disorders

Corcept Completes Enrollment in Phase 2 DAZALS Trial in Patients With Amyotrophic Lateral Sclerosis (ALS) (Yahoo Finance) - "Corcept Therapeutics Incorporated...today announced completion of enrollment in DAZALS, a randomized, double-blind, placebo-controlled Phase 2 trial of its proprietary selective cortisol modulator dazucorilant in patients with amyotrophic lateral sclerosis (ALS)....DAZALS enrolled 249 patients, randomized 1:1:1 to receive either 150 mg of dazucorilant, 300 mg of dazucorilant or placebo daily for 24 weeks. The study’s primary endpoint is change from baseline in the ALS Functional Rating Scale-Revised (ALSFRS-R), which measures motor impairment and functional deterioration in patients with ALS. Key secondary endpoints include overall survival and quality of life. DAZALS was conducted at sites in Europe, United States and Canada."

Enrollment closed • Amyotrophic Lateral Sclerosis • CNS Disorders

DAZALS: Dazucorilant in Patients With Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P2 | N=228 | Recruiting | Sponsor: Corcept Therapeutics | Trial completion date: Nov 2027 ➔ May 2027 | Trial primary completion date: May 2027 ➔ Oct 2024

Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

DAZALS: Dazucorilant in Patients With Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P2 | N=198 | Recruiting | Sponsor: Corcept Therapeutics | Trial completion date: Nov 2024 ➔ Nov 2027 | Trial primary completion date: May 2024 ➔ May 2027

Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

Glucocorticoid receptor antagonist CORT113176 attenuates motor and neuropathological symptoms of Huntington's disease in R6/2 mice. (PubMed, Exp Neurol) - "In female mice, we did not observe major effects of CORT113176 treatment on HD-related symptoms, with the exception of the anti-epileptic effects. We conclude that CORT113176 effectively delays several key symptoms related to the HD phenotype in male R6/2 mice and believe that GR antagonism may be a possible treatment option."

Journal • Preclinical • CNS Disorders • Epilepsy • Huntington's Disease • Movement Disorders • CLSPN,

Impact of Adverse Life Experiences on Postpartum Behavioral Changes via Glucocorticoid Signaling and Cortico-Cortical Pathway (ACNP 2023) - "We also investigated the effects of one-week post-delivery treatment with fluoxetine [selective serotonin reuptake inhibitor (SSRI)], ganaxolone [γ-aminobutyric acid type A receptor (GABAAR) modulator], and CORT113176 [glucocorticoid receptor (GR) antagonist] on postpartum behavioral changes in stressed dams (N=12). This study sheds light on the complex interplay between ALEs, sustained glucocorticoid signaling, and disturbed mental health during the postpartum period. Dysregulation of the HPA axis and the AI-PrL pathway may be involved in postpartum behavioral changes. Additionally, our mouse model shows promise as a valuable tool for investigating the pathological mechanisms underlying postpartum behavioral changes in mood and social cognition."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Depression • Psychiatry • FOS

Impact of Adverse Life Experiences on Postpartum Behavioral Changes via Glucocorticoid Signaling and Cortico-Cortical Pathway (ACNP 2023) - "We also investigated the effects of one-week post-delivery treatment with fluoxetine [selective serotonin reuptake inhibitor (SSRI)], ganaxolone [γ-aminobutyric acid type A receptor (GABAAR) modulator], and CORT113176 [glucocorticoid receptor (GR) antagonist] on postpartum behavioral changes in stressed dams (N=12). This study sheds light on the complex interplay between ALEs, sustained glucocorticoid signaling, and disturbed mental health during the postpartum period. Dysregulation of the HPA axis and the AI-PrL pathway may be involved in postpartum behavioral changes. Additionally, our mouse model shows promise as a valuable tool for investigating the pathological mechanisms underlying postpartum behavioral changes in mood and social cognition."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Depression • Psychiatry • FOS

Stress-induced Neuroinflammation of the Spinal Cord is Restrained by Cort113176 (Dazucorilant), A Specific Glucocorticoid Receptor Modulator. (PubMed, Mol Neurobiol) - "The effects of CORT113176 indicate that glucocorticoids are probably involved in neuroinflammation. Thus, modulation of the GR would become useful to dampen the inflammatory component of neurodegenerative disorders."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation • GFAP • HMGB1 • IL1B • ITGAM • NFKB1 • SOX9 • TLR4 • TNFA

DAZALS: Dazucorilant in Patients With Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P2 | N=198 | Recruiting | Sponsor: Corcept Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Amyotrophic Lateral Sclerosis • CNS Disorders