Osilodrostat, formerly known as LCI699, is an oral treatment that inhibits an enzyme called 11-beta-hydroxylase, which is involved in cortisol production. Blocking the enzyme prevents excessive cortisol production, thereby normalizing the hormone’s levels in the body, and reducing Cushing’s disease symptoms.
The therapy works in a similar manner as the commonly used treatment Metopirone (metyrapone), but with stronger inhibitory activity and better stability.
Osilodrostat, which was originally developed by Novartis but is now being developed by Recordati after it acquired the worldwide rights for marketing osilodrostat, will be available in three dosages: 1 milligram (mg), 5 mg, and 10 mg film-coated tablets.
In its recommendation, the EMA’s Committee for Medicinal Products for Human Use (CHMP) stated that the dosing should be initiated and supervised by physicians experienced in endocrinology or internal medicine, and that patients should be monitored.
Data from the LINC-3 Phase 3 trial (NCT02180217) showed that osilodrostat was superior to a placebo at keeping urinary cortisol levels under control — 86% of patients maintained their cortisol levels in urine, compared with 29% of those on placebo.
The trial included 137 people with persistent Cushing’s disease, who received osilodrostat for 26 weeks. Participants were then randomly selected to continue osilodrostat or switch to a placebo for an additional eight weeks.
The findings were shared at the Endocrine Society Annual Meeting (ENDO 2019) in a talk, titled “Osilodrostat Treatment in Cushing’s Disease (CD): Results from a Phase III, Multicenter, Double-Blind, Randomized Withdrawal Study (LINC 3).”
Investigators in an ongoing Phase 3 trial — called LINC-4 (NCT02697734) — are currently confirming their findings in 69 patients with persistent or recurrent Cushing’s disease, who were randomized to receive osilodrostat or a placebo. The study’s main aim is to determine the proportion of patients achieving a complete response — also measured by normal cortisol levels in urine.
An upcoming Phase 2 trial (NCT03708900) will test the safety and efficacy of osilodrostat in children with the disease who are ineligible for surgical treatment, have had disease recurrence after surgery, or are awaiting surgery.
So far, the most common side effects of osilodrostat treatment in adults are gastrointestinal disorders, edema (swelling), headache, and fatigue. The most serious common side effect is adrenal insufficiency.