Osilodrostat (LCI699) is a treatment that Novartis is developing for people with Cushing’s disease, a condition caused by excessive levels of the hormone cortisol.

Because of the promise it showed in preclinical-trial studies, the European Medicines Agency in 2014 granted Osilodrostat orphan drug status as a Cushing’s disease treatment.

Doctors make a distinction between Cushing’s syndrome and Cushing’s disease. When the adrenal gland produces excessive amounts of cortisol, the condition is called Cushing’s syndrome. When a pituitary gland tumor secretes excessive amounts of adrenal gland stimulating hormone, or ACTH, the disorder is referred to as Cushing’s disease.

How Osilodrostat works

Osilodrostat is an oral drug that inhibits an enzyme called 11-beta-hydroxylase that is involved in cortisol  production. Blocking the enzyme prevents excessive cortisol production, normalizing the hormone’s levels in the body and reducing Cushing’s disease symptoms.

Osilodrostat in clinical trials

Novartis is investigating Osilodrostat’s safety and effectiveness as a Cushing’s disease treatment in a Phase 2 clinical trial (NCT01331239) expected to be completed in 2018.

The company published findings that covered two patient groups in the journal Pituitary. They showed that Osilodrostat helped reduce cortisol levels in urine.

In the 22-week study, patients whose cortisol levels were more than three times the upper normal limit took an initial dose of either 4 mg/day or 10 mg/day of Osilodrostat. The dose was increased every two weeks to 60 mg/day until cortisol levels equaled or were below the upper normal limit.

The main objective of the study was to normalize cortisol levels or cut them in half from the start of the treatment to the 10th and 22nd weeks.

Osilodrostat reduced cortisol levels in all of the patients by week 22. Seventy-nine percent achieved normal cortisol levels by then. Even though patients tolerated the drug well, some experienced side effects. These included weakness, lack of energy, acne, and adrenal insufficiency, or the adrenal gland being unable to produce enough hormones.

Novartis is also investigating Osilodrostat’s safety and effectiveness as a Cushing’s disease therapy in a multi-center, randomized, double-blind, placebo-controlled Phase 3 trial (NCT02697734).

The company is recruiting participants for the trial, which it expects to complete by 2019.

Novartis is assessing Osilodrostat as a treatment for Cushing’s syndrome in an open-label, multicenter Phase 2 trial (NCT02468193).

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