Operational Vice President, Clinical Research Sumitomo Pharma America Brisbane, CA, United States
Introduction: Data from the SPIRIT long-term extension (LTE) demonstrated durability of treatment effect and tolerability for up to 104 weeks with once-daily relugolix combination therapy (Relugolix-CT: relugolix 40mg, estradiol 1mg and norethindrone acetate 0.5mg) for endometriosis-associated pain. Concerns about bone mineral density (BMD) loss (–0.45% at 104 weeks) prompted evaluation of the benefit/risk profile of Relugolix-CT over time. Methods: Efficacy and safety data from the Institutional Review Board approved, 24-week SPIRIT 1&2 studies, and the 80-week SPIRIT LTE were analyzed as cumulative incidence of time to benefit, defined as time to first minimal-to-no dysmenorrhea (Numerical Rating Scale score less than or equal to 1) and time to harm, defined as time to first BMD loss greater than 3% from baseline at the lumbar spine. Results: Among 799 women, minimal-to-no dysmenorrhea was observed as early as 8 weeks in 56.3% of women, which increased to 94.5% at Week 52 and was sustained through 104 weeks (95.3%). Time to first BMD loss greater than 3% was observed in 13.1% of women at Week 24, 15.5% at Week 52, and 21.5% at Week 104. Z-scores remained within range for age. Conclusion/Implications: With 104 weeks of data, the benefit/risk profile of Relugolix-CT remains favorable. The benefit of resolving a key symptom of endometriosis in nearly all patients outweighs the risk of BMD loss greater than 3%, in a subset that was maintained within range for age. Relugolix-CT helps address an important clinical need for effective and well-tolerated medical treatments for endometriosis that can be used longer term.
Disclosure(s):
Rachel B. Wagman, MD: No financial relationships to disclose
Neil Johnson, MD: Abbott: Consultant (Ongoing), Speaker/Honoraria (Ongoing); Guerbet: Consultant (Ongoing), Speaker/Honoraria (Ongoing), University Grants/Research Support (Ongoing); Myovant Sciences: Advisory Committee/Board Member (Ongoing), Consultant (Ongoing), Grant/Research Support (Ongoing), Speaker/Honoraria (Ongoing)
Andrea S. Lukes, MD: Abbvie: Grant/Research Support (Ongoing); Merck: Grant/Research Support (Ongoing); Mylan: Grant/Research Support (Ongoing); Myovant: Grant/Research Support (Ongoing), Speaker/Honoraria (Ongoing); Organon: Grant/Research Support (Ongoing)
Yulan (Juliet) Li, PhD: No financial relationships to disclose
Felicia Cosman, MD: Amgen/UCB: Advisory Committee/Board Member (Ongoing), Consultant (Ongoing), Speaker/Honoraria (Ongoing); Biocon: Consultant (Ongoing); Enterabio: Advisory Committee/Board Member (Ongoing), Consultant (Ongoing); Pfizer/Myovant: Consultant (Ongoing); Radius Health: Speaker/Honoraria (Ongoing), University Grants/Research Support (Ongoing)