The agreement also covers Signifor (pasireotide), an approved treatment for adults with Cushing’s disease who failed surgery or who were not eligible for surgery, and Signifor LAR, approved for both Cushing’s and acromegaly.
“We are extremely pleased with the agreement reached with Novartis for the acquisition of the rights to Signifor and osilodrostat, fundamental treatments for patients suffering from Cushing’s disease and acromegaly and for whom surgery is not a viable solution,” Andrea Recordati, the company’s CEO, said in a press release.
Following the terms of the agreement, Recordati will pay a total $390 million to Novartis for the acquisition of global rights to the three therapies. Novartis also will receive additional payments pending approval and market access of osilodrostat, as well as royalties on sales of this new therapy.
“These important additions to our product portfolio of treatments for severe rare diseases represent a key and historical milestone for Recordati, reaffirming the continuation of the successful execution of its strategy to become a true global player in the treatment of rare diseases and to continue providing innovative therapeutic solutions for patients with rare serious conditions and unmet medical needs, which is the core of our mission,” Recordati added.
Signifor was first approved by the U.S. Food and Drug Administration in 2012 for the treatment of adults with Cushing’s disease for whom standard pituitary surgery is not an option, or has not been curative.
It contains the active substance pasireotide, which is a somatostatin analogue. This active compound blocks the production and release of some hormones, including the adrenocorticotropic hormone ACTH. That hormone promotes the release of cortisol, and the development of Cushing’s disease.
Osilodrostat is an investigational, orally available therapy designed to inhibit 11Beta-hydroxylase, an enzyme responsible for the final step of cortisol synthesis in the adrenal glands. Blocking the enzyme prevents excessive cortisol production, normalizing the hormone’s levels in the body and reducing Cushing’s disease symptoms.
Novartis presented promising data from osilodrostat at the recent Endocrine Society Annual Meeting (ENDO 2019), showing the treatment was superior to placebo at keeping urinary cortisol levels under control.
The LINC-3 Phase 3 trial (NCT02180217) included 137 people with persistent Cushing’s disease, who received osilodrostat for 26 weeks. The participants were then randomly selected to continue osilodrostat or switch to a placebo for an additional eight weeks.
The study aimed to determine if osilodrostat was better than a placebo at maintaining a response in urinary cortisol levels, which it did. Data showed that 86% of patients maintained their cortisol levels in urine, compared with 29% of those on placebo.
An ongoing Phase 3 trial — called LINC-4 (NCT02697734) — is now confirming the findings in 69 patients with persistent or recurrent Cushing’s disease. In this trial, patients with be randomly selected to receive osilodrostat or a placebo right from the beginning. The main objective is to determine the proportion of patients achieving a complete response — also measured by normal cortisol levels in urine.
An upcoming Phase 2 trial also will assess 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.
Novartis has filed marketing authorization applications for osilodrostat with the European and U.S. regulatory agencies.