RARE Daily

Recordati Reports Positive Results from Late-Stage Cushing’s Disease Study

March 23, 2021

Rare Daily Staff

Recordati Rare Diseases reported positive results from the phase 3 LINC 4 study of Isturisa in patients with Cushing’s disease at the Endocrine Society’s Annual Meeting.

Results from LINC 4, the first phase 3 study, demonstrated that Isturisa provided rapid and sustained normalization of mean urinary free cortisol levels (mUFC). Normalizing mUFC levels represents an important treatment goal that can potentially reduce morbidity, improve quality of life, and restore the life expectancy of patients with Cushing’s disease towards that of the general population, the company said.

Cushing’s syndrome is a rare disorder caused by chronic exposure to excess levels of cortisol. Cushing’s syndrome arises as a result of excess secretion of adrenocorticotropic hormone from a pituitary adenoma, a tumor of the pituitary gland. There is often a delay in diagnosing Cushing’s syndrome, which consequently leads to a delay in treating patients. Patients who are exposed to excess levels of cortisol for a prolonged period have increased comorbidities associated with the cardiovascular and metabolic systems, which consequently reduce quality of life and increase the risk of mortality.

Isturisa is an oral inhibitor of 11β-hydroxylase, which catalyzes the final step of cortisol synthesis in the adrenal glands. Isturisa is available as 1 mg, 5 mg and 10 mg film-coated tablets. Isturisa is approved for the treatment of adult patients with endogenous Cushing’s syndrome in the EU and is now available in France, Germany, Greece and Austria.

The LINC 4 study enrolled adult patients with persistent, recurrent, or de novo Cushing’s disease who had mUFC at the upper limit of normal. A total of 73 patients received randomized treatment with Isturisa or placebo during the initial 12-week, double-blind, placebo-controlled period. Of those, 48 patients were included in the Isturisa arm and 25 patients in the placebo arm. All patients received open-label Isturisa after week 12 until the end of the core study (week 48).

The study met its primary endpoint of a significantly higher proportion of patients achieving normal mUFC levels with Isturisa than with placebo at the end of the initial 12-week placebo-controlled phase (77 percent vs 8 percent). Median time to first controlled mUFC response was 35 days.

Recordati said the key secondary endpoint was also met, with the majority (81 percent) of patients having normal mUFC levels at week 36. The rapid and sustained reductions in mUFC levels were accompanied by improvements in cardiovascular and metabolic-related parameters, including systolic and diastolic blood pressure and glycated hemoglobin (HbA1c), at both week 12 and the end of the core study.

Isturisa was well tolerated in LINC 4, further supporting the manageable safety profile established in previous studies. The most common adverse events reported up to data cut-off were arthralgia (45 percent), decreased appetite (45 percent), fatigue (38 percent), nausea (37 percent) and headache (33 percent). Hypocortisolism-related AEs were reported in 27 percent of patients. Most hypocortisolism-related adverse events were of mild or moderate severity, were managed with dose reduction, dose interruption, and/or additional therapy, and did not require discontinuation of Isturisa treatment.

“These data add to the robust body of evidence supporting Isturisa as an effective and well-tolerated treatment for patients with Cushing’s disease,” said Andrea Recordati, CEO of Recordati. “Recordati is committed to improving the lives of patients with this serious yet underserved condition.”

Photo: Andrea Recordati, CEO Recordati

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