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J Heart Lung Transplant. 2016 Feb;35(2):213-21. doi: 10.1016/j.healun.2015.08.012. Epub 2015 Sep 3.

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

Author information

Department of Respiratory Medicine, Hannover Medical School, Biomedical Research in End stage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Germany. Electronic address:
Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado at Denver Health Sciences Center, Aurora, Colorado.
Center for Thoracic Transplantation at the Heart & Lung Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ.
Department of Respiratory Medicine, Royal Perth Hospital, Perth, Australia.
Department of Pneumology, Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitaetsklinikum Essen GmbH, Essen, Germany.
Departemnt of Medicine, Loyola University Medical Center, Maywood, IL, USA.
Department of Medicine, New York-Presbyterian Hospital/Columbia University Medical Center, New York, NY.
Department of Pediatrics, University of Tennessee Center for Health Sciences, Memphis, Tennessee.
Alnylam Pharmaceuticals, Cambridge, Massachusetts.
Lung Transplant Unit, St. Vincent's Hospital, Darlinghurst, New South Wales, Australia.



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.


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.


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.


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.


RNA interference; bronchiolitis obliterans; community-acquired infections; lung transplantation; respiratory syncytial virus; ribavirin

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