Incidence of Mood Disorders in Women Treated With Linzagolix: 52-week Results From Two Phase 3 Trials

INTRODUCTION: Safety data from two Phase 3 trials of linzagolix, a GnRH receptor antagonist, for the treatment of women with uterine fibroids (UFs) for 52 weeks were reviewed for treatment emergent adverse events (TEAEs) of depression and other mood disorders. We note that the incidence of TEAEs of depression and other mood disorders, previously reported up to 24 weeks, was low and revealed no consistent drug-related pattern. METHODS: PRIMROSE 1 and 2 are randomized, double-blind, placebo-controlled Phase 3 trials investigating the efficacy and safety of linzagolix 100 mg and 200 mg once daily, with and without hormonal add-back therapy (ABT) in women with UFs. After 24 weeks, the placebo group in PRIMROSE2 was switched to 200 mg+ABT. The incidence of depression and other mood disorder TEAEs from week 24 to week 52 was assessed using the Standardized MedDRA Query for Depression and suicide/self-injury and adding TEAEs of anxiety. RESULTS: Safety data from 336 and 421 patients, in PRIMROSE1 and PRIMROSE2, respectively, were collected from week 24 to week 52. Mood swings were reported for one (1.1%) subject in PRIMROSE2, and anxiety was reported in one (1.1%) subject in PRIMROSE1, both in the placebo/200 mg+ABT group. Depression was reported in one (1.1%) subject in PRIMROSE2 in the 200 mg/200 mg+ABT group. There were no reports of suicidal ideation, affect lability, or altered mood. CONCLUSION: The low incidence of depression and other mood disorder TEAEs was maintained up to 52 weeks of treatment with linzagolix. Linzagolix appears to be well tolerated in women with symptomatic UFs.