clofutriben (SPI-62) / Sparrow Pharma, Astellas - LARVOL DELTA

Small-Molecule Strategies for Polymyalgia Rheumatica and Giant Cell Arteritis in Older Adults. (PubMed, Molecules) - "Clinical evidence highlights that JAK inhibitors, particularly upadacitinib for GCA and tofacitinib or baricitinib for PMR, demonstrate the potential to induce remission and significantly reduce the required GC burden in a subset of patients. Although methotrexate remains the primary csDMARD, its modest overall efficacy suggests it should be reserved for patients with definitive contraindications or restricted access to JAK inhibitors. Furthermore, novel therapies like clofutriben demonstrate potential in reversing GC-induced morbidities without compromising disease control. Ultimately, integrating targeted small-molecule immunomodulators establishes a crucial therapeutic paradigm that attempts to maximize clinical remission while safeguarding the physiological integrity of geriatric patients against severe GC toxicities."

Journal • Review • Geriatric Disorders • Giant Cell Arteritis • Immunology • Inflammation • Musculoskeletal Pain • Pain • Rheumatology

Analysis of Cardiometabolic Effects from A Randomized, Placebo-Controlled, Clinical Trial of Clofutriben in Adults with Diabetes (ENDO 2026) - P2a | "For each parameter, observed clofutriben benefits were numerically larger in the EC-enriched subset. Our results support that clofutriben may provide more substantial cardiometabolic benefits in patients with T2D prospectively selected for EC."

Clinical • Diabetes • Diabetic Neuropathy • Hematological Disorders • Immune Thrombocytopenic Purpura • Metabolic Disorders • Peripheral Neuropathic Pain • Thrombocytopenia • Thrombocytopenic Purpura • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

SAT-634 - Prevalence of Elevated Cortisol in Difficult-to-Control Type 2 Diabetes: Interim Results for CAPTAIN-T2D, a Phase 2 Trial of Clofutriben (ENDO 2026) - "Methods Approximately 1500 participants in this response-adaptive-randomized, placebo-controlled, dose-range finding trial with DTC T2D (HbA1c ≥7.5% despite ≥2 ADMs and either use of ≥3 ADMs or ≥2 antihypertensives or presence of a diabetes complication, osteoporosis, or prior CS diagnosis ) will be assessed by overnight dexamethasone suppression test (DST) at approximately 50 US sites...Replication of these results in DTC T2D confirms the high unmet need in cardiometabolic disease. The specific etiology of these elevations and the full results of the blinded intervention, including response of HbA1c, body habitus, BP, lipids, and other cardiometabolic risk factors to CLO must await the trial's completion (expected Q4 2027)."

Late-breaking abstract • P2 data • Cardiovascular • Cushing’s Disease • Diabetes • Diabetic Neuropathy • Endocrine Disorders • Hypertension • Metabolic Disorders • Osteoporosis • Type 2 Diabetes Mellitus

Cardiometabolic Effects of Clofutriben (CLO) in Adults with Type 2 Diabetes (T2D): A Six-Week, Phase 2, Placebo-Controlled, Randomized Clinical Trial (ADA 2026) - P2a | "CLO benefits on HbA1c, glucose, TC, and TG were evident in the ITT population. Larger numerical benefit in those parameters, and favorable trends in BP and weight, were observed in the EC-enriched subset. These results suggest potential for more substantial cardiometabolic benefits in patients with T2D and EC treated with CLO."

Clinical • P2 data • Diabetes • Diabetic Neuropathy • Metabolic Disorders • Type 2 Diabetes Mellitus

ACSPIRE: SPI-62 as a Treatment for Hypercortisolism Related to a Benign Adrenal Tumor (clinicaltrials.gov) - P2 | N=30 | Completed | Sponsor: Sparrow Pharmaceuticals | Terminated ➔ Completed

Trial completion • Adrenal Cortex Carcinoma • Cushing’s Disease • Endocrine Disorders • Solid Tumor

DDI: Pharmacokinetic Interaction Trial of Clofutriben With Midazolam and Prednisolone (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Sparrow Pharmaceuticals | Active, not recruiting ➔ Completed | Trial completion date: Apr 2026 ➔ Dec 2025

Trial completion • Trial completion date

Trial Against INtractable Type 2 Diabetes (CAPTAIN-T2D) (clinicaltrials.gov) - P2 | N=1500 | Recruiting | Sponsor: Sparrow Pharmaceuticals

New P2 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Clofutriben Pharmacokinetics in Patients With Impaired Renal Function (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: Sparrow Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Renal Disease

Human Adipose Tissue 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibition Without Tachyphylaxis by Clofutriben, a Pseudo-Irreversible Enzyme Inhibitor. (PubMed, Clin Transl Sci) - "Molecular docking revealed that clofutriben can form a ternary complex with nicotinamide-adenine dinucleotide phosphate (NADPH) cofactor and the human HSD-1 active site. The higher activation energy to dissociate that trimolecular interaction, compared to a bimolecular drug-enzyme interaction characteristic of other HSD-1 inhibitors, is posited to be responsible for the enzyme kinetic and favorable pharmacological properties of clofutriben."

Journal • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Oncology • Type 2 Diabetes Mellitus

Effects of clofutriben, a selective 11β-hydroxysteroid dehydrogenase type 1 inhibitor, on the efficacy and toxicity of prednisolone in patients with polymyalgia rheumatica: a single-blind controlled trial with sequential cohorts. (PubMed, Ann Rheum Dis) - "Further trials to assess clofutriben's potential to improve the benefit-risk profile of prednisolone are warranted."

Journal • Cardiovascular • Giant Cell Arteritis • Immunology • Metabolic Disorders • Musculoskeletal Pain • Pain • Rheumatology

Clofutriben Pharmacokinetics in Patients With Impaired Renal Function (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: Sparrow Pharmaceuticals

New P1 trial • Renal Disease

DDI: Pharmacokinetic Interaction Trial of Clofutriben With Midazolam and Prednisolone (clinicaltrials.gov) - P1 | N=16 | Active, not recruiting | Sponsor: Sparrow Pharmaceuticals

New P1 trial

RESCUE: SPI-62 as a Treatment for Adrenocorticotropic Hormone-dependent Cushing's Syndrome (clinicaltrials.gov) - P2 | N=26 | Completed | Sponsor: Sparrow Pharmaceuticals | Active, not recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ Aug 2025 | Trial primary completion date: Dec 2025 ➔ Aug 2025

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

A Trial of Prednisolone in Combination With SPI-62 in Participants With Polymyalgia Rheumatica (PMR) (clinicaltrials.gov) - P1 | N=1 | Terminated | Sponsor: Sparrow Pharmaceuticals | N=24 ➔ 1 | Suspended ➔ Terminated; lack of enrollment

Enrollment change • Trial termination • Giant Cell Arteritis • Immunology • Musculoskeletal Pain • Pain • Rheumatology

A Trial of Prednisolone in Combination With SPI-62 or Placebo in Subjects With Polymyalgia Rheumatica (PMR) (clinicaltrials.gov) - P2 | N=66 | Completed | Sponsor: Sparrow Pharmaceuticals | Recruiting ➔ Completed | Trial completion date: Jul 2025 ➔ Apr 2025

Trial completion • Trial completion date • Giant Cell Arteritis • Immunology • Musculoskeletal Pain • Pain • Rheumatology

RESCUE: SPI-62 As a Treatment for Adrenocorticotropic Hormone-dependent Cushing's Syndrome (clinicaltrials.gov) - P2 | N=26 | Active, not recruiting | Sponsor: Sparrow Pharmaceuticals | Trial primary completion date: Dec 2024 ➔ Dec 2025

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

ACSPIRE: SPI-62 As a Treatment for Hypercortisolism Related to a Benign Adrenal Tumor (clinicaltrials.gov) - P2 | N=30 | Terminated | Sponsor: Sparrow Pharmaceuticals | Trial completion date: Dec 2025 ➔ Feb 2025 | Active, not recruiting ➔ Terminated; Data does not demonstrate a clear benefit for this patient population, and we therefore cannot justify continuing this trial.

Trial completion date • Trial termination • Adrenal Cortex Carcinoma • Cushing’s Disease • Endocrine Cancer • Endocrine Disorders • Oncology • Solid Tumor

A Trial of Prednisolone in Combination With SPI-62 in Participants With Polymyalgia Rheumatica (PMR) (clinicaltrials.gov) - P1 | N=24 | Suspended | Sponsor: Sparrow Pharmaceuticals | Trial completion date: Oct 2024 ➔ Apr 2025 | Trial primary completion date: Oct 2024 ➔ Apr 2025

Combination therapy • Trial completion date • Trial primary completion date • Giant Cell Arteritis • Immunology • Musculoskeletal Pain • Pain • Rheumatology • CRP

A Trial of Prednisolone in Combination With SPI-62 or Placebo in Subjects With Polymyalgia Rheumatica (PMR) (clinicaltrials.gov) - P2 | N=72 | Recruiting | Sponsor: Sparrow Pharmaceuticals | N=48 ➔ 72 | Trial completion date: Jul 2024 ➔ Jul 2025 | Trial primary completion date: Apr 2024 ➔ Apr 2025

Combination therapy • Enrollment change • Trial completion date • Trial primary completion date • Giant Cell Arteritis • Immunology • Musculoskeletal Pain • Pain • Rheumatology • CRP

A Trial of Prednisolone in Combination With SPI-62 in Participants With Polymyalgia Rheumatica (PMR) (clinicaltrials.gov) - P1 | N=24 | Suspended | Sponsor: Sparrow Pharmaceuticals | Recruiting ➔ Suspended

Combination therapy • Trial suspension • Giant Cell Arteritis • Immunology • Musculoskeletal Pain • Pain • Rheumatology • CRP

THE 11Β-HYDROXYSTEROID DEHYDROGENASE TYPE 1 INHIBITOR SPI-62 DIFFERENTIALLY MODULATES PREDNISOLONE IMMUNE AND MUSCULOSKELETAL EFFICACY AND BONE FORMATION/RESORPTION BIOMARKERS IN PATIENTS WITH POLYMYALGIA RHEUMATICA (PMR): AN INTERIM REPORT (EULAR 2024) - "SPI-62 achieved full HSD-1 inhibition. SPI PSL 10 attenuated PMR disease control, which was partly restored by SPI PSL 15 and further by SPI PSL 20. Relapses, ESR, IL-6, stiffness intensity, and pain chronicity were numerically the same with SPI PSL 20 as PBO PSL 10."

Biomarker • Clinical • Fatigue • Giant Cell Arteritis • Immunology • Muscular Atrophy • Musculoskeletal Diseases • Musculoskeletal Pain • Obesity • Pain • Rheumatology • CRP • IL6

A Trial of Prednisolone in Combination With SPI-62 in Participants With Polymyalgia Rheumatica (PMR) (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Sparrow Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Giant Cell Arteritis • Immunology • Musculoskeletal Pain • Pain • Rheumatology • CRP

ACSPIRE: SPI-62 as a Treatment for Hypercortisolism Related to a Benign Adrenal Tumor (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: Sparrow Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=150 ➔ 30

Enrollment change • Enrollment closed • Adrenal Cortex Carcinoma • Cushing’s Disease • Endocrine Cancer • Endocrine Disorders • Oncology • Solid Tumor

RESCUE: SPI-62 as a Treatment for Adrenocorticotropic Hormone-dependent Cushing's Syndrome (clinicaltrials.gov) - P2 | N=26 | Active, not recruiting | Sponsor: Sparrow Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Cushing’s Disease • Endocrine Disorders

A Trial of Prednisolone in Combination With SPI-62 in Participants With Polymyalgia Rheumatica (PMR) (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Sparrow Pharmaceuticals

New P1 trial • Giant Cell Arteritis • Immunology • Musculoskeletal Pain • Pain • Rheumatology • CRP