First patient enters extension study of SPI-62

Sparrow Pharmaceuticals shares update about Phase 2 open-label trial RESCUE

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by Andrea Lobo |

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The first patient has opted to enter the open-label extension study of a Phase 2 trial testing SPI-62 in people with adrenocorticotropic hormone (ACTH)-dependent forms of Cushing’s syndrome, including Cushing’s disease.

The announcement was made by SPI-62’s developer, Sparrow Pharmaceuticals, which is conducting a Phase 2 trial called RESCUE (NCT05307328) to evaluate the safety, efficacy, and pharmacological properties of the experimental therapy.

“We’re excited to graduate patients from the initial RESCUE study to a new phase of investigation of SPI-62, one which will allow us to deepen our understanding of the potential for long-term safety and efficacy of this completely novel mode of treatment for Cushing’s,” Frank Czerwiec, MD, PhD, chief medical officer at Sparrow, said in a press release.

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Cushing’s patients report high disease burden, despite treatment

RESCUE is recruiting adults, both men and non-menstruating women, with a diagnosis of ACTH-dependent Cushing’s syndrome, across approximately 16 sites in the U.S., Bulgaria, and Romania.

It plans to enroll 26 patients, who will be assigned randomly to receive either SPI-62 or a placebo, once daily, for 12 weeks (about three months). After completing the first 12 weeks of treatment, patients assigned originally to receive SPI-62 will switch to placebo, while those initially given a placebo will receive SPI-62 for another 12 weeks.

SPI-62 efficacy will be assessed by measuring cortisol activation in the liver, one of its key target organs. The treatment’s effect on other Cushing’s features, including high blood pressure, blood sugar levels, body fat content, muscle strength, mood, and sleep, also will be evaluated.

Patients who complete this initial phase of the study can opt to enroll in an open-label long-term extension of the trial, which seeks to obtain data on the safety and tolerability of the treatment in the long term.

Cushing’s syndrome is caused by an excess of cortisol, a steroid hormone produced by the adrenal glands that sit atop the kidneys. It is commonly caused by tumors in the brain’s pituitary gland that trigger the excessive production of ACTH, which signals the adrenal glands to produce cortisol. This specific form of the syndrome is called Cushing’s disease.

“Cushing’s syndrome can be life-threatening, and the preferred first-line surgical treatment often fails. While medical therapies are increasingly used, there are many drawbacks and innovative medical approaches have lagged,” Czerwiec said.

How SPI-62 works in a Cushing’s patient

SPI-62 is an oral treatment designed to lower cortisol levels by blocking the activity of an enzyme called HSD-1. This enzyme converts an inactive form of cortisol, called cortisone, into the active form of the hormone. According to Sparrow, this strategy “could represent the first new mechanism of action to treat Cushing’s syndrome in decades.”

In preclinical studies, the treatment was able to block HSD-1 activity in the brain, liver, and fat tissue, which are particularly susceptible to the effects of cortisol. These tissues and organs also are frequently linked to Cushing’s symptoms.

According to the company, in previous clinical trials SPI-62 has shown a positive safety and tolerability profile with few adverse effects reported. It also was found capable of targeting HSD-1 in the brain and liver, and to reduce cortisol levels in the liver. In healthy volunteers, the HSD-1 inhibition brought on by SPI-62 reduced the ratio of active-to-inactive cortisol in the liver by 90%.

Other testing of SPI-62

Sparrow also is testing SPI-62 in combination with prednisolone in patients with polymyalgia rheumatica, an inflammatory disorder often treated with glucocorticoids — medications that mimic the action of cortisol in the body. A Phase 2 trial (NCT05436652) is testing whether SPI-62 can reduce the side effects associated with glucocorticoid treatment in these patients without affecting their effectiveness.

Another Phase 2 trial (NCT05436639) is assessing the affects of SPI-62 in people with other diseases associated with high cortisol levels, including autonomous cortisol secretion. In that condition, excessive production of cortisol is driven by tumors or other adrenal gland abnormalities.