Baloxavir Marboxil (BXM) Treatment of Influenza in Renally Impaired Patients: Post Hoc Analysis of CAPSTONE-2

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Background: Renally impaired patients (pts) have a higher mortality rate from influenza vs pts without renal impairment. In the US, oseltamivir (OSL) is used for influenza but requires dose adjustment for pts with creatinine clearance (CrCl) <60 mL/min. CAPSTONE-2 (NCT02949011), a global phase 3 study of BXM vs OSL vs placebo (PBO) in high-risk pts ≥12 years with influenza, demonstrated the efficacy and safety of prompt single dose BXM treatment: median time to improvement of influenza symptoms (TTIIS) was (BXM vs OSL vs PBO) 73.2 vs 81.0 vs 102.3 h; no new safety signals were identified. This post hoc analysis examined BXM efficacy and safety in renally impaired pts with influenza. Methods: In CAPSTONE-2, pts received a single oral dose of BXM (40 mg: <80 kg, 80 mg: ≥80 kg), OSL 75 mg twice daily for 5 days or PBO and were to be excluded if CrCl was <60 mL/min (<30 mL/min for Japan). At the time of enrolment, a small cohort of renally impaired pts was deemed eligible for inclusion as judged by the PI and were included in the intention to treat infected (ITTI) population. For this study, renal impairment was CrCl <55 mL/min. Endpoints were TTIIS, time to alleviation of symptoms (TTAS), time to cessation of viral shedding (TCVS) and safety. Results: Overall, 89/1153 (7.7%) renally impaired pts were in the ITTI population; 33/384 (8.6%), 23/386 (6.0%), and 33/383 (8.6%) received BXM, OSL or PBO, respectively. For renally impaired pts, median TTIIS was numerically shorter for BXM (62.4 h [95% CI 29.2-86.2]) vs PBO (92.2 h [44.0-115.9]; p=0.1602) and similar vs OSL (69.4 h [45.5-123.2]; p=0.2061) with similar results for median TTAS (BXM: 62.4 h [29.2-86.2] vs PBO: 92.2 h [44.0-115.9]; p=0.1602; OSL: 78.2 h [48.8-123.2]; p=0.0729). Median TCVS was significantly shorter for BXM (48 h [24-72]) vs PBO (120 h [96-168]; p=0.0016) and OSL (96 h [96-144]; p=0.0029). Overall, 54 (34.2%) pts had ≥1 adverse event. Conclusions: In this analysis of renally impaired pts (CrCl 21.7 to 54.9 mL/min), there was clinical benefit of single dose BXM with a similar median TTIIS and TTAS as well as significantly better median TCVS vs OSL; analysis of the safety data from this small cohort did not identify any new safety concerns. Funding: Commercial Support - Genentech, Inc.

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