Sparrow Plans Trial of SPI-62 in Cushing’s Syndrome

Sparrow Pharmaceuticals is planning to launch a Phase 2 clinical trial to assess the safety and effectiveness of its investigational, lead small molecule HSD-1 inhibitor, SPI-62, in people with Cushing’s syndrome.

The trial is expected to open later this year, and it specifically will enroll people with ACTH-dependent Cushing’s syndrome who also have at least one of the following conditions: type 2 diabetes, impaired glucose (blood sugar) tolerance, or hyperlipidemia (abnormally high fat levels in the blood).

Researchers from Sparrow and other institutions shared details about the investigational medication and the upcoming trial in a poster titled, “SPI-62: An investigational HSD-1 inhibitor for the treatment of Cushing syndrome,” presented at the European Congress of Endocrinology 2021, held online May 22–26.

Cushing’s syndrome is caused by abnormally high levels of the stress-associated hormone cortisol. Excess cortisol production usually is caused by a tumor in the adrenal glands — where this hormone is made — or in the brain’s pituitary gland, which helps to coordinate adrenal gland activity. Cushing’s disease refers specifically to a type of Cushing’s syndrome caused by a pituitary tumor.

SPI-62 is an investigational compound that is designed to block the activity of an enzyme called 11 beta-hydroxysteroid dehydrogenase type 1 (HSD-1), which converts an inactive form of cortisol, called cortisone, into its active form.

The excess cortisol that causes problems in people with Cushing’s syndrome is “formed mostly by HSD-1,” according to David Katz, PhD, Sparrow’s chief scientific officer.

“SPI-62 can reduce that pool [of excess cortisol] 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,” Katz said in a press release.

According to Sparrow, 165 people without Cushing’s already have been given the investigational medication in early clinical trials. Data from these trials indicated that SPI-62 is active in the body following a once-daily oral dosing regimen and can safely lower cortisol levels in the liver.

Early clinical trial data also have demonstrated disease-relevant benefits in people with diabetes-related nerve damage (peripheral diabetic neuropathy), including clinically meaningful reductions in glucose and cholesterol levels.

“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.

The planned Phase 2 trial to test SPI-62 in people with Cushing’s syndrome will start recruiting participants later this year. To be eligible, participants will need to have urine tests that indicate they have relatively high HSD-1 activity, among other criteria. No other Cushing’s-specific treatments will be permitted, though participants are allowed to continue taking medications to manage symptoms of other health conditions.

Following enrollment, patients will be assigned randomly to receive either the active medication followed by a placebo, or vice versa. Researchers will  examine the effects of treatment on various disease-relevant measures, including blood pressure, levels of fat and other molecules in the blood, and participants’ quality of life.

“This will be the first randomized placebo-controlled trial of a HSD-1 inhibitor in the treatment of [Cushing’s syndrome],” the researchers wrote.

According to Jacks, Sparrow also is planning additional clinical trials to test SPI-62 in other health conditions where it might be beneficial, including in individuals who are taking a steroid medicine for polymyalgia rheumatica, an inflammatory disorder characterized by muscle pain and stiffness, particularly in the shoulders and hips.