A phase 2, randomized, double-blind, placebo-controlled trial of presatovir for the treatment of respiratory syncytial virus upper respiratory tract infection in hematopoietic-cell transplant recipients.

Chemaly RF, Dadwal SS, Bergeron A, Ljungman P, Kim YJ, Cheng GS, Pipavath SN, Limaye AP, Blanchard E, Winston DJ, Stiff PJ, Zuckerman T, Lachance S, Rahav G, Small CB, Mullane KM, Patron RL, Lee DG, Hirsch HH, Waghmare A, McKevitt M, Jordan R, Guo Y, German P, Porter DP, Gossage DL, Watkins TR, Marty FM, Chien JW, Boeckh M.


RSV treatment options are currently limited, and various RSV antivirals are currently under clinical development. Presatovir (GS-5806) is an oral RSV fusion inhibitor with potent and selective anti-RSV activity in vitro and a terminal half-life of ~34 hours. During a human challenge study, presatovir reduced RSV viral load and severity of clinical disease. A phase 2, randomized, double-blind, placebo-controlled trial was conducted to assess the safety, tolerability and efficacy of presatovir among HCT patients with RSV URTI. In total, 189 patients with diagnosed RSV URTI ≤6 days and without new abnormalities on a chest X-ray <48 hours before start of study treatment were recruited. Patients received presatovir 2000 mg (4 x 50 mg tablets) or placebo orally or by nasogastric tube on days 1, 5, 9, 13, and 17, and were followed through day 28. Presatovir had a favorable safety profile, but the co-primary endpoints (time-weighted average change in nasal viral load between day 1-9 and proportion of patients that developed lower respiratory tract complications between day 1-28) were not achieved. However, in a post-hoc exploratory analysis, significantly more patients with lymphopenia (<200 cells/µL) developed lower respiratory tract complications in the placebo group. This interesting finding suggests that antiviral treatment might be beneficial in RSV URTI patients with most severe T-cell defect to prevent deterioration to severe LRTI.

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