Positive results from the Phase III LINC 4 study have confirmed the efficacy and safety of osilodrostat, an oral therapy for patients with Cushing’s disease. The results were published in The Journal of Clinical Endocrinology & Metabolism. Recordati Rare Diseases is marketing the drug as ISTURISA®.
The LINC 4 study augments the efficacy and safety data for ISTURISA in patients with Cushing’s disease, confirming the results from the Phase III LINC 3 study. This study in 73 adults, a Phase III study of a medical treatment in patients with Cushing’s disease included an upfront, randomized, double-blind, placebo-controlled period during which 48 patients received ISTURISA and 25 received placebo for the first 12 weeks, followed by an open-label period during which all patients received ISTURISA until week 48; thereafter, patients could enter an optional extension phase.
Key findings published in the manuscript entitled ‘Randomised trial of osilodrostat for the treatment of Cushing’s disease’ include:
- LINC 4 met the primary endpoint: ISTURISA was significantly superior to placebo at normalizing mUFC at the end of a 12-week randomized, double-blind period (77% vs 8%; P<0.0001).
- Effects of ISTURISA were rapid. Over one-quarter of patients randomized to ISTURISA achieved normal mUFC as early week 2 and 58% achieved control by week 5.
- The key secondary endpoint was also met, with 81% of all patients in the study having normal mUFC at week 36.
- Improvements in cardiovascular and other clinical signs of Cushing’s disease, including blood pressure and blood glucose metabolism, were seen by week 12 and were maintained throughout the study.
- Physical features of hypercortisolism improved during ISTURISA treatment, including fat pads, facial rubor, striae, and muscle wasting. Improvements were observed by week 12, with continued improvement throughout the study to week 48.
- Patient-reported QoL scores (CushingQoL and Beck Depression Inventory) also improved during ISTURISA treatment.
- ISTURISA was well tolerated in the majority of patients, with no unexpected adverse events (AEs). The most common AEs overall were decreased appetite, arthralgia, fatigue, and nausea.
“These results show convincingly that osilodrostat is an effective treatment for Cushing’s disease,” said Peter J. Snyder MD, professor of Medicine at the University of Pennsylvania. “Osilodrostat rapidly lowered cortisol excretion to normal in most patients with Cushing’s disease and maintained normal levels throughout the core phase of the study. Importantly, this normalization was accompanied by improvements in cardiovascular and metabolic parameters, which increase morbidity and mortality in Cushing’s disease.”