Xeris Unveils New Analysis on Recorlev® for Cushing’s Syndrome at ENDO 2024

Xeris Biopharma Holdings, Inc. recently presented a post-hoc analysis of its SONICS study on the effects of levoketoconazole (Recorlev®) in adults with Cushing’s syndrome at ENDO 2024 in Boston. The analysis highlighted the relationship between baseline mean urinary free cortisol (mUFC) levels and treatment outcomes with Recorlev.

The study found that patients with lower baseline mUFC levels experienced higher rates of cortisol normalization, required lower maintenance doses of Recorlev, and had reduced incidences of liver-related adverse events. These findings underscore the importance of personalized medical management for patients with Cushing’s syndrome.

The SONICS study had previously demonstrated the efficacy of Recorlev in normalizing cortisol levels across varying severities of Cushing’s syndrome. The post-hoc analysis included 92 patients who were stratified into three groups based on their baseline mUFC levels: Group 1 (≤ 2.5x the upper limit of normal (ULN)), Group 2 (>2.5x to ≤ 5x ULN), and Group 3 (>5x ULN).

Group 2 showed the highest mUFC response rate at 36.4%, followed by Group 1 at 31.6% and Group 3 at 23.8%. The results indicated that higher baseline mUFC levels were associated with a lower response to Recorlev treatment.

The study also revealed that Group 3 required higher average daily doses of Recorlev compared to Group 1 and Group 2. Specifically, Group 3 used a nominally higher average daily dose of 631 mg during maintenance therapy, as opposed to 475 mg for Group 1 and 548 mg for Group 2.

Furthermore, Group 3 experienced more liver-related adverse events and a higher incidence of liver test abnormalities compared to Groups 1 and 2. This group had a 14% incidence of liver-related adverse events, compared to 7.9% for Group 1 and 3.0% for Group 2. Additionally, Group 3 had a higher rate of discontinuation due to adverse events (24%) compared to Group 1 (12%) and Group 2 (16%).

The findings suggest that lower baseline mUFC levels are associated with better treatment outcomes, lower maintenance dose requirements, and fewer liver-related adverse events. These insights emphasize the need for individualized treatment plans for patients with Cushing’s syndrome.

Cushing’s syndrome is a rare and potentially fatal endocrine disorder caused by prolonged exposure to elevated cortisol levels, often due to a benign tumor in the pituitary gland. The condition predominantly affects adults aged 30-50 and is more common in women. Symptoms include menstrual irregularities, difficulty conceiving, excessive male hormones leading to hirsutism, oily skin, and acne. The disease also has severe multisystem complications, including metabolic changes, high blood pressure, diabetes, and psychological disturbances. If left untreated, the five-year survival rate is approximately 50%.

Recorlev is a cortisol synthesis inhibitor approved for the treatment of endogenous hypercortisolemia in adult patients with Cushing’s syndrome who cannot undergo surgery or for whom surgery has not been curative. The drug has been shown to significantly reduce mean urinary free cortisol levels in clinical studies. Recorlev received approval from the US FDA in December 2021 and has been granted orphan drug designation both in the US and Europe for the treatment of endogenous Cushing's syndrome.

The post-hoc analysis of the SONICS study provides valuable insights into the efficacy and safety of Recorlev, reinforcing its potential as a treatment option for patients with Cushing’s syndrome, particularly those with lower baseline mUFC levels.