Lead Therapeutic Targeting the Main Source of Cortisol Toxicity to be Studied in Phase 2 Trial for Cushing Syndrome
- Sparrow’s lead proprietary small molecule SPI-62 reduces intracellular cortisol, the main cause of morbidity in Cushing syndrome.
- SPI-62 was associated with few, mostly mild, adverse effects in four prior clinical trials.
- In subjects with diabetic peripheral neuropathy, SPI-62 showed clinically meaningful separation from placebo on HbA1c, glucose, cholesterol, and triglycerides.
- The company plans to initiate multiple Phase 2 trials with SPI-62 in the coming 12 months.
PORTLAND, Ore.–(BUSINESS WIRE)–#ECE2021—Sparrow Pharmaceuticals, an emerging clinical-stage biopharmaceutical company developing novel, targeted therapies for disorders of steroid excess, presented new data at the European Congress of Endocrinology 2021 (e-ECE 2021) on 22-26 May 2021 as a poster presentation, “SPI-62: An investigational HSD-1 inhibitor for the treatment of Cushing syndrome.” The presentation summarized the mechanism of action, safety, and preliminary efficacy of the company’s lead therapeutic, SPI-62, an oral, small molecule, novel 11β-hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor. The poster also introduced a Phase 2, international, multicenter clinical trial in Cushing syndrome (CS) that is planned to start later in 2021.
Excess cortisol in CS causes toxicity predominantly by interaction with intracellular receptors. Sparrow’s novel approach to treatment of CS is based on recognition that the predominant source of intracellular cortisol is HSD-1. SPI-62, a potent and selective HSD-1 inhibitor, has demonstrated the ability to reduce intracellular cortisol in the liver by 90%.
Results of four Phase 1 and Phase 2 clinical trials in which SPI-62 was administered to 165 individuals showed:
- Pharmacokinetics supportive of once-daily oral dosing.
- Full and sustained intracellular cortisol reduction in liver and target engagement in brain.
- Generally good safety and tolerability at and above the anticipated clinical dose.
- At six weeks in subjects with peripheral diabetic neuropathy, separation from placebo of 0.5% on HbA1c, 1.64 mM on glucose, 0.77 mM on cholesterol, and 0.42 mM on triglycerides.
“The excess cortisol that harms patients with Cushing syndrome is the intracellular pool with access to intracellular receptors. That’s formed mostly by HSD-1,” said Dr. David Katz, Chief Scientific Officer of Sparrow. “SPI-62 can reduce that pool by up to 90% and was associated with favorable clinical changes in patients with diabetes. We’re excited to learn how those data might translate to clinical benefit for patients with Cushing syndrome, for whom excess cortisol is the primary causal factor of their disease.”
The planned Phase 2, double-blind, randomized, placebo-controlled, international trial of SPI-62 for the treatment of CS will begin recruitment later in 2021. Sparrow will seek subjects with confirmed diagnosis of ACTH-dependent CS and at least one of the following: type 2 diabetes, impaired glucose tolerance, or hyperlipidemia.
“SPI-62 has the potential to address the devastating effects of excess steroids in several different patient populations,” said Robert Jacks, President and CEO of Sparrow. “In parallel with this trial in CS we plan to initiate a trial in patients with autonomous cortisol secretion, and another in patients taking a steroid medicine for polymyalgia rheumatica. Our recently completed Series A financing provides the opportunity to rapidly demonstrate the potentially transformative benefits of addressing the toxicities of excess intracellular corticosteroids through HSD-1 inhibition.”
About Sparrow Pharmaceuticals
Sparrow Pharmaceuticals was founded to spare patients the ravages of steroids. Leveraging underappreciated scientific insights into corticosteroid biology, the company is working to provide better treatment options for serious disorders of hypercortisolism, and to revolutionize the treatment of autoimmune and inflammatory conditions. Its lead product, SPI-62, is an oral, small molecule, novel therapeutic treatment designed to target the source of active intracellular corticosteroids in key tissues.
Contacts
Terri Clevenger
Westwicke, an ICR Company
Terri.clevenger@westwicke.com
203 856-4326