Efficacy

Isturisa (Osilodrostat) for Cushing's Syndrome

Isturisa (osilodrostat) is an oral medication approved by the FDA for the treatment of adults with Cushing's syndrome who cannot undergo pituitary gland surgery or have undergone the surgery but still have the disease. Cushing's syndrome is a hormonal disorder caused by prolonged exposure of the body's tissues to high levels of the hormone cortisol. Isturisa works by inhibiting an enzyme called 11-beta-hydroxylase, which is involved in cortisol production. Clinical trials have demonstrated that Isturisa effectively reduces cortisol levels in urine and saliva in patients with Cushing's syndrome, thereby alleviating the symptoms associated with cortisol excess.

The efficacy of Isturisa was primarily evaluated in a study involving 137 adult patients with Cushing's disease. In the LINC 3 trial, a significant proportion of patients achieved normal urinary free cortisol (UFC) levels with Isturisa treatment at the end of a 24-week period. Moreover, sustained reductions in UFC were observed in an extension phase, indicating the drug's long-term efficacy. Patients also reported improvements in clinical signs and symptoms, such as hypertension and weight gain, which are common in Cushing's syndrome.

Recorlev (Levoketoconazole) for Cushing's Syndrome

Recorlev (levoketoconazole) is another medication approved for the treatment of endogenous Cushing's syndrome in adults who are not candidates for surgery or have not responded to surgery. Levoketoconazole is a stereoisomer of ketoconazole and functions as an adrenal steroidogenesis inhibitor. By inhibiting enzymes involved in cortisol synthesis, Recorlev effectively reduces cortisol levels. Clinical studies have shown that Recorlev can lead to normalization or substantial reduction of cortisol levels in the majority of patients with Cushing's syndrome.

The efficacy of Recorlev was evaluated in a Phase 3 trial, SONICS, which was a multicenter, open-label study. The study demonstrated that a significant number of patients achieved normal mean 24-hour urinary free cortisol levels after six months of maintenance therapy without a dose increase. This normalization of cortisol levels suggests that Recorlev can be an effective treatment option for patients with Cushing's syndrome, particularly when surgery is not feasible or has been unsuccessful.