ALN-RSV01 for prevention of bronchiolitis obliterans syndrome after respiratory syncytial virus infection in lung transplant recipients Journal Article

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Authors: Gottlieb, J.; Zamora, M. R.; Hodges, T.; Musk, A. W.; Sommerwerk, U.; Dilling, D; Arcasoy, S.; DeVincenzo, J.; Karsten, V.; Shah, S; Bettencourt, B. R.; Cehelsky, J.; Nochur, S.; Gollob, J.; Vaishnaw, A.; Simon, A. R.; Glanville, A. R.
Article Title: ALN-RSV01 for prevention of bronchiolitis obliterans syndrome after respiratory syncytial virus infection in lung transplant recipients
Abstract: BACKGROUND: Respiratory syncytial virus (RSV) infection in lung transplant (LTx) patients is associated with an increased incidence of bronchiolitis obliterans syndrome (BOS). ALN-RSV01 is a small interfering RNA targeting RSV replication that was shown in an earlier Phase 2a trial to be safe and to reduce the incidence of BOS when compared with placebo. METHODS: We performed a Phase 2b randomized, double-blind, placebo-controlled trial in RSV-infected LTx patients to examine the impact of ALN-RSV01 on the incidence of new or progressive BOS. Subjects were randomized (1:1) to receive aerosolized ALN-RSV01 or placebo daily for 5 days. RESULTS: Of 3,985 symptomatic patients screened, 218 were RSV-positive locally, of whom 87 were randomized to receive ALN-RSV01 or placebo (modified intention-to-treat [mITT] cohort). RSV infection was confirmed by central laboratory in 77 patients (ALN-RSV01, n = 44; placebo, n = 33), which comprised the primary analysis cohort (central mITT [mITTc]). ALN-RSV01 was found to be safe and well-tolerated. At Day 180, in ALN-RSV01-treated patients, compared with placebo, in the mITTc cohort there was a trend toward a decrease in new or progressive BOS (13.6% vs 30.3%, p = 0.058), which was significant in the per-protocol cohort (p = 0.025). Treatment effect was enhanced when ALN-RSV01 was started 5 days from symptom onset, and was observed even without ribavirin treatment. There was no significant impact on viral parameters or symptom scores. CONCLUSIONS: These results confirm findings of the earlier Phase 2a trial and provide further support that ALN-RSV01 reduces the risk of BOS after RSV in LTx recipients.
Journal Title: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
ISSN: 1557-3117; 1053-2498
Publisher: International Society for Heart and Lung Transplantation. Published by Elsevier Inc  
Date Published: 2015
Language: ENG
DOI/URL:

S1053-2498(15)01387-X
Notes: LR: 20151011; CI: Copyright (c) 2015; JID: 9102703; OTO: NOTNLM; 2015/04/03 [received]; 2015/07/20 [revised]; 2015/08/22 [accepted]; aheadofprint