On March 6, Recordati ’s Isturisa (osilodrostat) was granted FDA approval for Cushing’s Disease (CD). The drug is a direct inhibitor of 11-beta-hydroxylase enzyme and prevents the production of cortisol, the abnormally raised biomarker of CD.

This approval brings new hope and innovation to the disease space as it is the first drug to directly target the 11-beta hydroxylase enzyme, inhibiting the synthesis of cortisol. This unique mechanism is set to bring great commercial and clinical value to both the drug and the company, which secured the worldwide rights for the drug from Novartis in 2019. Cushing’s Disease is a rare disorder characterised by an excess production of cortisol in the body due to the excretion of adrenocorticotropic hormone (ACTH) by a benign pituitary tumour. This causes the adrenal glands to produce abnormal levels of cortisol, leading to further complications such as diabetes mellitus and obesity.

Key opinion leaders (KOLs) interviewed by GlobalData have noted the need for drugs with greater safety and efficacy profiles, as many CD treatments lack clinical value and have large side effect profiles. Furthermore, there is a huge gap in the market for a drug that acts directly to reduce cortisol synthesis. Isturisa meets these unmet needs with its mechanism of action and a positive safety profile. Having been granted orphan drug status in 2014, the drug was granted approval by the European Medicines Agency (EMA) in early 2020 prior to its FDA approval for CD. Novartis had aimed to widen the indication label for Isturisa, but trials in chronic heart failure did not succeed. In 2019, Novartis sold the rights for Isturisa and other CD drugs, Signifor (pasireotide) and prolonged release Signifor, to Recordati for $390M.

Recordati is set to see commercial success with Isturisa, as the Phase III LINC-3 clinical trial results showed 50% of CD patients saw normalized cortisol levels after 24 weeks with Isturisa, with 86% of patients maintaining these levels compared to a maintenance rate of 30% with placebo. Isturisa is aimed at a subpopulation of CD patients who are not eligible for pituitary surgery, or for those who have undergone these surgeries but still have the disease.

Novartis is also trialling Isturisa in children ages 6–18 years with CD. The Phase II trial is expected to complete in 2023. The main competitor for Isturisa is set to reach the market soon after Isturisa. Strongbridge ’s Recorlev (levoketoconazole) is close to completion in its Phase III trial for CD, and the developer is expected to apply for a New Drug Application in mid-2020. The drug has a differing mechanism of action as a steroidogenesis inhibitor, but its positive effects on both cortisol levels and biomarkers of cardiac risk mean that it will be a strong contender in the CD market.