The European Medicine Agency‘s Committee for Orphan Medicinal Products (COMP) has recommended that Corcept Therapeutics‘ relacorilant receive orphan drug designation for the treatment of Cushing’s syndrome, the company announced in a press release.
The European Commission is expected to accept the recommendation by the end of the month. Relacorilant received the same designation in the U.S. in October 2018.
Orphan drug status is intended to encourage therapies for rare and serious diseases through benefits such as 10-year market exclusivity in the European Union upon approval, reduced fees, and access to the EU’s centralized marketing authorization procedure.
Endogenous Cushing’s syndrome patients have a complication — usually a benign tumor — that causes the body to produce too much cortisol hormone. The excessive amount of circulating cortisol can lead to serious problems, such as type 2 diabetes and high blood pressure.
Relacorilant is designed to prevent the effects of excess cortisol by blocking one of its receptors, the glucocorticoid receptor. Findings from a Phase 2 trial (NCT02804750) — on which the recommendation was based — suggested that the treatment may be faster and safer than approved medications for managing the effects of prolonged cortisol excess in Cushing’s patients.
The trial recruited 30 patients, given escalating doses of relacorilant for a total of 12 weeks. The first group received the lowest dose — 100 mg/day of relacorilant for four weeks, followed by 150 mg/day for four weeks, and then 200 mg/day for the final four weeks. A second group, called the high-dose cohort, was given a similar regimen but with a starting dose of 250 mg/day and a final dose of 350 mg/day.
Interim results showed that patients in the low-dose group had a significant improvement in their glucose tolerance and a 60% increase in a marker of bone health. The treatment also reduced blood pressure in 45% of patients with uncontrolled high blood pressure from cortisol excess.
Relacorilant also led to weight loss and improved additional health parameters, including liver function, cognition, and decreased insulin resistance, and had a general positive effect on quality of life.
Importantly, the effects of 12 weeks of treatment with relacorilant were similar to those seen after six months of treatment with Korlym (mifepristone), an approved medicine for Cushing’s patients, but without its known side effects.
Safety data showed a positive profile overall, with no evidence of serious adverse effects and no affinity toward the progesterone receptor — a major drawback of Korlym.
“The sponsor has provided clinical data that demonstrate that the product can reduce blood pressure and improve control of hyperglycaemia in patients who were not adequately managed by currently authorised products,” reads the COMP’s letter of recommendation. “The Committee considered that this constitutes a clinically relevant advantage.”
Based on these positive findings, Corcept has launched the Phase 3 GRACE trial (NCT03697109), a multicenter, double-blind, placebo-controlled, randomized-withdrawal study, to evaluate relacorilant’s safety and effectiveness in patients with endogenous Cushing’s syndrome and concurrent type 2 diabetes mellitus, impaired glucose tolerance, and/or uncontrolled high blood pressure.
The trial is recruiting participants at 60 clinical sites in the United States, Canada, Europe, and Israel and will be conducted in two stages. Initially, all patients will receive oral, once-daily relacorilant for 22 weeks, at doses ranging from 100 mg to 400 mg.
Those who complete this first stage and show improvements in pre-specified parameters of glucose tolerance or blood pressure will move into the second, randomized phase of the trial. Patients will randomly receive either placebo or relacorilant at the same dose they received at the end of the first stage. This new round of treatment will last 12 weeks.
GRACE’s main goals are to measure changes in glucose tolerance and blood pressure between the end of the first and second stages of the study. Researchers will also evaluate treatment-related adverse events for up to 48 weeks.
Secondary objectives include identifying the proportion of patients achieving a response in glucose tolerance and high blood pressure criteria, the proportion of those who worsened at the end of the first stage, and the changes in quality of life throughout the study.