Isturisa (osilodrostat) / Novartis, Recordati - LARVOL DELTA

EFFICACY AND SAFETY OF ALDOSTERONE SYNTHASE INHIBITORS IN HYPERTENSION: A META-ANALYSIS OF NINE RANDOMIZED CONTROLLED TRIALS (ACC 2026) - " We systematically identified nine randomized controlled trials (RCTs) evaluating ASIs (osilodrostat, vicadrostat, lorundrostat, baxdrostat) compared with placebo. ASIs lower BP effectively, even in resistant hypertension, with acceptable safety but a moderate hyperkalemia risk, warranting further large-scale outcome trials."

Retrospective data • Cardiovascular • Hypertension

ALDOSTERONE SYNTHASE INHIBITORS FOR RESISTANT OR UNCONTROLLED HYPERTENSION: A NETWORK META-ANALYSIS OF RANDOMIZED CLINICAL TRIALS (ACC 2026) - "Baxdrostat, Lorundrostat, and Osilodrostat significantly reduced SBP (Baxdrostat: MD −8.81, 95% CI −10.94 to −6.67; Lorundrostat: MD −8.42, 95% CI −11.05 to −5.78; Osilodrostat: MD −6.78, 95% CI −9.64 to −3.92) and DBP (Baxdrostat: MD −3.14, 95% CI −5.24 to −1.03; Lorundrostat: MD −3.23, 95% CI −5.32 to −1.13; Osilodrostat: MD −2.58, 95% CI −5.13 to −0.02). ASIs significantly lowered SBP and DBP in patients with resistant hypertension without increasing the risk of serious adverse events. These findings suggest ASIs may represent a promising therapeutic option for resistant hypertension."

Retrospective data • Cardiovascular • Hypertension

International Real-world study on osilodrostat efficacy and safety in adrenal Cushing syndrome. (PubMed, J Clin Endocrinol Metab) - "Osilodrostat controls hypercortisolism in 66.7% of patients with adrenal CS treated for longer than 4 weeks and in 87.5% of cases treated for longer than 12 weeks, with a positive impact on blood pressure and body weight. Patients who received osilodrostat after other previous steroidogenesis inhibitors have a higher probability of response."

Journal • Real-world evidence • Adrenal Cortex Carcinoma • Cushing’s Disease • Endocrine Disorders • Genito-urinary Cancer • Oncology • Solid Tumor

Use of osilodrostat in a block-and-replace and titration strategy for cushing's syndrome: a position paper by French experts. (PubMed, Rev Endocr Metab Disord) - No abstract available

Journal • Review • Cushing’s Disease • Endocrine Disorders

Osilodrostat for the treatment of Cushing syndrome: an update. (PubMed, Expert Rev Endocrinol Metab) - "Osilodrostat is an effective and well-tolerated therapy that leads to significant reductions in cortisol secretion and improves metabolic, cardiovascular, and psychological outcomes in patients with CS. Real-world studies support its efficacy across different forms and severities of endogenous hypercortisolism."

Journal • Review • Cardiovascular • Cushing’s Disease • Endocrine Disorders

More on Osilodrostat for Bilateral Adrenal Hypercortisolism in Primary Aldosteronism. (PubMed, N Engl J Med) - No abstract available

Journal • Endocrine Disorders

More on Osilodrostat for Bilateral Adrenal Hypercortisolism in Primary Aldosteronism. Reply. (PubMed, N Engl J Med) - No abstract available

Journal • Endocrine Disorders

Impact of 1 mg Osilodrostat Therapy on Mild Autonomous Cortisol Secretion (MACS) (clinicaltrials.gov) - P2 | N=15 | Recruiting | Sponsor: Mayo Clinic | Not yet recruiting ➔ Recruiting

Enrollment open

Management of Known Cushing's Disease in a Nonsurgical Candidate Secondary to a History of Hemorrhagic Stroke Case Report. (PubMed, Case Rep Endocrinol) - "She developed a deep venous thrombosis (DVT) in the right lower extremity and was placed on enoxaparin. The clinical manifestations found in this case are largely due to hypercortisolism, and while she is going to still have additional testing including biopsy of the fibroid, colorectal surgical evaluation for hemorrhoids, and genetic testing with confirmatory lab work per endocrinology outpatient, her illness was medically uncontrolled. As osilodrostat takes a couple weeks to a couple months for full control with frequent cortisol checks, adjustments including insulin, blood pressure control, electrolyte corrections, and more should be considered."

Journal • Cardiovascular • Cerebral Hemorrhage • Cushing’s Disease • Diabetes • Endocrine Disorders • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hypertension • Metabolic Disorders • Musculoskeletal Diseases • Oncology • Orthopedics • Pain • Respiratory Diseases • Solid Tumor • Thrombosis • Type 2 Diabetes Mellitus • Uterine Leiomyoma

Aldosterone synthase inhibitors for resistant or uncontrolled hypertension: a network meta-analysis of randomized clinical trials. (PubMed, J Hypertens) - "Highly selective ASIs (Baxdrostat and Lorundrostat) significantly lowered BP in patients with resistant hypertension without increasing the risk of serious adverse events, whereas the nonselective agent Osilodrostat did not reach the significant difference. These findings suggest that selective aldosterone synthase inhibition represents a promising therapeutic option for resistant hypertension."

Clinical • Journal • Retrospective data • Cardiovascular • Hypertension

Osilodrostat for Cyclic Cushing Disease. (PubMed, AACE Endocrinol Diabetes) - "If a surgical cure is not possible, a medication that treats hypercortisolism with rapid onset, reversible inhibition, and minimal side effects would be ideal to address the cyclicity. Our case is the first to our knowledge demonstrating osilodrostat's use for native cyclic Cushing syndrome treatment and highlighted its reversibility and ability to preserve normal adrenal function."

Journal • Cushing’s Disease • Endocrine Disorders • Fatigue • Nephrology • Renal Disease

Pharmacokinetic (PK), Pharmacodynamic (PD) and Tolerability of Osilodrostat in Pediatric Patients With Cushing's Syndrome (clinicaltrials.gov) - P2 | N=12 | Recruiting | Sponsor: RECORDATI GROUP | Trial completion date: Nov 2025 ➔ Jul 2027 | Trial primary completion date: Nov 2025 ➔ Jul 2027

Trial completion date • Trial primary completion date • Cushing’s Disease • Endocrine Disorders • Pediatrics

Isturisa Treatment in Mild Autonomous Cortisol Secretion( MACS) (clinicaltrials.gov) - P4 | N=10 | Recruiting | Sponsor: Johns Hopkins University | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2028 ➔ Mar 2029 | Trial primary completion date: Jun 2028 ➔ Dec 2028

Enrollment open • Trial completion date • Trial primary completion date

Efficacy and safety of osilodrostat for the treatment of Cushing's syndrome (PubMed, Zhonghua Nei Ke Za Zhi) - No abstract available

Journal • Cushing’s Disease • Endocrine Disorders

Update and practical recommendations for the use of medical treatment of Cushing´s syndrome. (PubMed, Endocr Rev) - "Currently available medical treatments include adrenal steroidogenesis inhibitors that block cortisol secretion (ketoconazole, levoketoconazole, metyrapone, osilodrostat, mitotane, and etomidate), drugs that modulate pituitary ACTH secretion (pasireotide and cabergoline), and drugs that block peripheral glucocorticoid receptors (mifepristone). In this review, we summarize the main indications for medical treatment in CS, the mechanism of drug action, efficacy, recommended doses, and safety of the currently available drugs, as well as potential future treatments. We also discuss titration and block-and-replace approaches for control of hypercortisolism and provide recommendations for the use and monitoring of medical treatment in CS, including patients with endogenous hypercortisolism in special situations such as pregnancy, cyclic CS and mild autonomous cortisol secretion."

Journal • Cushing’s Disease • Endocrine Disorders

Case Report: Ectopic Cushing's syndrome caused by a pancreatic neuroendocrine tumor managed through dual steroidogenesis inhibition and endoscopic ultrasound-guided ethanol ablation. (PubMed, Front Endocrinol (Lausanne)) - "This case demonstrates the effectiveness of dual steroidogenesis blockade with etomidate and osilodrostat in both the acute and chronic management of severe ectopic Cushing's syndrome due to pNET. It also highlights the role of endoscopic ethanol ablation as a minimally invasive curative option for patients who are unfit for surgery."

Journal • Cushing’s Disease • Diabetes • Endocrine Disorders • Gastrointestinal Neuroendocrine Tumor • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Psychiatry • Solid Tumor

The effect of hypercortisolism treatment on dyslipidemia in Cushing syndrome: systematic review and meta-analysis. (PubMed, J Clin Endocrinol Metab) - "Our study demonstrate a significant improvement in serum lipid levels after treatment of CS. Since the cardiovascular complications of hypercortisolism depend on several factors, further studies are needed to determine whether this directly translates into an adequate reduction in the risk of major cardiovascular events."

Journal • Retrospective data • Cardiovascular • Cushing’s Disease • Dyslipidemia • Endocrine Disorders • Metabolic Disorders

Isturisa Treatment in Mild Autonomous Cortisol Secretion( MACS) (clinicaltrials.gov) - P4 | N=10 | Not yet recruiting | Sponsor: Johns Hopkins University | Trial primary completion date: Dec 2026 ➔ Jun 2028

Trial primary completion date

Controlling cortisol excess and comorbidities in Cushing's syndrome with osilodrostat. (PubMed, Pituitary) - No abstract available

Journal • Cushing’s Disease • Endocrine Disorders

Executive summary of the consensus document for the management of severe Cushing's syndrome: Consensus document of the Neuroendocrinology Focus Group of the Spanish Society of Endocrinology and Nutrition (SEEN). (PubMed, Endocrinol Diabetes Nutr (Engl Ed)) - "Combination therapy with ketoconazole and metyrapone is a useful option for these patients. Prompt treatment of comorbidities and thrombo- and infection prophylaxis are recommended. In conclusion, a rapid control of hypercortisolism is vital in SCS, and for this purpose combination therapy or potent drugs with a rapid onset of action such as etomidate or osilodrostat are indicated."

Clinical guideline • Journal • Cushing’s Disease • Endocrine Disorders • Infectious Disease

Delirium Induced by Rapid Titration of Osilodrostat in a Patient With Cushing's Disease: A Case Report. (PubMed, Cureus) - "We report a woman in her early 40s with a history of major depressive disorder treated with clomipramine. The episode suggests that abrupt cortisol fluctuations may induce psychiatric symptoms even under hydrocortisone supplementation. Clinicians should avoid rapid titration and ensure close collaboration between endocrinology and psychiatry when psychiatric symptoms arise during treatment."

Journal • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Cushing’s Disease • Depression • Endocrine Disorders • Infectious Disease • Major Depressive Disorder • Nephrology • Psychiatry • Renal Disease • Suicidal Ideation

Osilodrostat for Cushing's Syndrome of Unknown Etiology: A Case Report Beyond Pituitary, Ectopic, or Adrenal Carcinoma Origins (ASHP 2025) - No abstract available

Case report • Clinical • Adrenal Cortex Carcinoma • Cushing’s Disease • Endocrine Disorders • Genito-urinary Cancer • Oncology • Solid Tumor

MOMACS: Metyrapone Versus Osilodrostat in Patients With Metabolic Autonomous Cortisol Secretion (MACS) (clinicaltrials.gov) - P4 | N=150 | Recruiting | Sponsor: Laikο General Hospital, Athens

New P4 trial

Successful non-surgical treatment of bilateral macronodular adrenocortical disease with osilodrostat. (PubMed, Endokrynol Pol) - "Not required for Clinical Vignette."

Journal • Cushing’s Disease • Endocrine Disorders

Efficacy and safety of osilodrostat in patients with ectopic Cushing´s syndrome. a real-world study in Spain. (PubMed, J Endocrinol Invest) - No abstract available

Journal • Real-world evidence • Cushing’s Disease • Endocrine Disorders