SPI-62 / Sparrow Pharma - LARVOL DELTA

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

RESCUE: SPI-62 as a Treatment for Adrenocorticotropic Hormone-dependent Cushing's Syndrome (clinicaltrials.gov) - P2 | N=26 | Recruiting | Sponsor: Sparrow Pharmaceuticals | Trial primary completion date: Dec 2023 ➔ Dec 2024

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

A Trial of Prednisolone in Combination With SPI-62 or Placebo in Subjects With Polymyalgia Rheumatica (PMR) (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: Sparrow Pharmaceuticals | Trial completion date: Dec 2023 ➔ Jul 2024 | Trial primary completion date: Sep 2023 ➔ Apr 2024

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

Characterization of Numeric Rating Scales for Symptom Assessment in Polymyalgia Rheumatica (ACR Convergence 2023) - "Clinical trial participants with PMR, no or low disease activity, and who received prednisolone 10 mg for = 1 week prior to entry were treated with prednisolone 10 mg for 4 weeks and received each of SPI-62 and matching placebo as adjunctive therapy for 2 weeks... The results provide necessary initial evidence to encourage further examination of these NRS' psychometrics. They suggest high patient compliance for daily symptom report and moderate test-retest reliability. Patient ability to recall accurately their most severe symptoms during 7 days prior to a trial visit was strong for stiffness and fatigue, whilst moderate for pain."

Fatigue • Giant Cell Arteritis • Immunology • Musculoskeletal Pain • Pain • Rheumatology

Population Target-Mediated Pharmacokinetic/Pharmacodynamic Modeling to Evaluate SPI-62 Exposure and Hepatic 11β-Hydroxysteroid Dehydrogenase Type 1 (HSD-1) Inhibition in Healthy Adults. (PubMed, Clin Pharmacokinet) - "A population TMDD-PD model that explains SPI-62 nonlinear PK and hepatic HSD-1 inhibition following different dose regimens in healthy adults was successfully established. Our simulation results provide a solid foundation for model-informed development of SPI-62."

Journal • PK/PD data

ACSPIRE: SPI-62 as a Treatment for Hypercortisolism Related to a Benign Adrenal Tumor (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: Sparrow Pharmaceuticals | Trial completion date: Dec 2023 ➔ Dec 2025 | Initiation date: Jun 2022 ➔ Jul 2023 | Trial primary completion date: Nov 2023 ➔ Dec 2024

Trial completion date • Trial initiation date • Trial primary completion date • Adrenal Cortex Carcinoma • 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 | Recruiting | Sponsor: Sparrow Pharmaceuticals | Trial completion date: Aug 2023 ➔ Dec 2025 | Trial primary completion date: Mar 2023 ➔ Dec 2023

Trial completion date • Trial primary completion date • Endocrine Disorders

Intracellular Cortisol Control: An Approach to Reduce Cushing's Syndrome Morbidity With Minimal Adrenal Insufficiency Risk? (ENDO 2023) - "Morning serum (293.9 +/- 18.9 v 273.4 +/- 39.3 nM) and 24h urinary (100.7 +/- 6.9 v 89.6 +/- 14.0 nmol) cortisol did not differ between SPI-62 and placebo...In situations that require GC rescue dosing during HSD-1 inhibitor administration, prodrug GCs (i.e., cortisone acetate, prednisone) will not be effective a. s they require HSD-1 for activation. Those patients require active agents (e.g., hydrocortisone, prednisolone).*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation...Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*"

Cardiovascular • Endocrine Disorders • Giant Cell Arteritis • Hypertension • Immunology • Musculoskeletal Pain • Myositis • Nephrology • Obesity • Osteoporosis • Pain • Renal Disease • Rheumatology

IN VIVO MEASUREMENT OF POTENT AND DURABLE HUMAN ADIPOSE 11Β-HYDROXYSTEROID DEHYDROGENASE TYPE 1 INHIBITION BY SPI-62 (EULAR 2023) - "Background 11β-hydroxysteroid dehydrogenase type 1 (HSD-1), an intracellular enzyme that converts glucocorticoids (GC) from inactive (e.g., prednisone, cortisone) to active (e.g., prednisolone, cortisol) form is a main source of intracellular GC that can bind to intracellular GC, mineralocorticoid, and non-genomic receptors. The selected regimen for that trial, SPI-62 6 mg QD, is appropriate to assess clinical effects that might be associated with adipose HSD-1 inhibition. Data from all 12 participants will be used to model dose-exposure-response relationships to refine dose selection for future clinical trials."

Preclinical • Diabetes • Giant Cell Arteritis • Immunology • Metabolic Disorders • Musculoskeletal Pain • Pain • Rheumatology • Type 2 Diabetes Mellitus

"Sparrow Pharmaceuticals Presents ePoster on SPI-62 at the 25th European Congress of Endocrinology https://t.co/sNCns8fPY2" (@NewsFromBW)

A Study to Assess 11 Beta-hydroxysteroid Dehydrogenase Type 1 Inhibition in Adipose Tissue by SPI-62 (clinicaltrials.gov) - P1 | N=12 | Active, not recruiting | Sponsor: Sparrow Pharmaceuticals | Completed ➔ Active, not recruiting | Trial completion date: May 2022 ➔ Dec 2023

Enrollment closed • Trial completion date • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Importance of target-mediated drug disposition (TMDD) of small-molecule compounds and its impact on drug development - example of the class effect of HSD-1 inhibitors. (PubMed, J Clin Pharmacol) - "The main purpose of the current review is to increase the awareness of TMDD in a series of small-molecule inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (HSD-1) using ABT-384, SPI-62, MK0916, BMS-823778, and BI-187004 as case examples. Recognizing TMDD in small-molecule compounds is important as the information can be leveraged to select the appropriate dose regimen, improve clinical trial design, as well as predict pharmacological target occupancy. In this review, we summarize the general pharmacokinetic features that facilitate recognition of small-molecule TMDD, provide case examples of specific HSD-1 inhibitors, highlight the importance of recognizing TMDD of small-molecule compounds during clinical development, and comment on the importance of utilizing pharmacometric modeling to facilitate quantitative understanding of small-molecule compounds exhibiting TMDD."

Journal

Toward Safer Glucocorticoid Therapy (ACR Convergence 2022) - "SPI-62 prevented several CORT adverse effects in mouse, demonstrating that blockade of local intracellular glucocorticoid activation by a HSD-1 inhibitor in target tissues can mitigate glucocorticoid toxicity. These results suggest that SPI-62 has potential to similarly mitigate adverse effects of glucocorticoid medications in human. A placebo-controlled Phase 2 clinical trial in patients with polymyalgia rheumatica has been initiated to compare prednisolone effects with and without SPI-62.Table: Observed percentage difference of treatment group mean, compared to control group mean, in CORT-treated mice"

Endocrine Disorders • Giant Cell Arteritis • Immunology • Musculoskeletal Pain • Obesity • Pain • Rheumatology

A Study to Assess 11 Beta-hydroxysteroid Dehydrogenase Type 1 Inhibition in Adipose Tissue by SPI-62 (clinicaltrials.gov) - P1 | N=12 | Completed | Sponsor: Sparrow Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

A Trial of Prednisolone in Combination With SPI-62 or Placebo in Subjects With Polymyalgia Rheumatica (PMR) (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: Sparrow Pharmaceuticals | Not yet recruiting ➔ Recruiting

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