A Phase 2b, Randomized, Double-blind, Placebo-Controlled Multicenter Study Evaluating Antiviral Effects, Pharmacokinetics, Safety, and Tolerability of Presatovir in Hematopoietic Cell Transplant Recipients with Respiratory Syncytial Virus (RSV) Infection of the Lower Respiratory Tract

Marty, Francisco M; Chemaly, Roy F; Mullane, Kathleen M; Lee, Dong-Gun; Hirsch, Hans H; Small, Catherine B; Bergeron, Anne; Shoham, Shmuel; Ljungman, Per; Waghmare, Alpana; Blanchard, Elodie; Kim, Yae-Jean; McKevitt, Matt; Porter, Danielle P; Jordan, Robert; Guo, Ying; German, Polina; Boeckh, Michael; Watkins, Timothy R; Chien, Jason W; Dadwal, Sanjeet S

The lack of clinical benefit in this study may also relate to the selected clinical endpoints, which occurred at lower-thananticipated rates that decreased power to detect a treatment effect. Although all subjects enrolled in the current study met Waghmare et al's criteria for proven or probable LRTI, median number of supplemental oxygen-free days through day 28 was much higher (26 and 28 days for presatovir-treated and placebo-treated patients, respectively, vs 17 days), and fewer patients required >2 L/min supplemental oxygen at baseline (35.6% versus 57%) relative to patients who presented with or developed LRTI in the Waghmare study [3] . Furthermore, lymphopenia is a major risk factor for RSV infection and subsequent poor outcomes in HCT recipients [2, 4, 29] , but only 4/47 patients with available data in the current study were lymphopenic (<200 cells/mm 3 ) at baseline, possibly because RSV infection occurred relatively late after HCT (median, 485 vs 129 days in the Waghmare study). These differences could be due to limited enrollment of patients perceived as fragile because of the requirement for lower respiratory sampling to confirm RSV LRTI. Enrichment of the study population for immunosuppressed patients should be considered in future clinical trials of therapies for RSV infection in HCT recipients.