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

Gottlieb, Jens; Zamora, Martin R.; Hodges, Tony; Musk, A.W.; Sommerwerk, Urte; Dilling, Daniel F.; Arcasoy, Selim M.; DeVincenzo, John P.; Karsten, Verena; Shah, Shaily; Bettencourt, Brian R.; Cehelsky, Jeffrey; Nochur, Saraswathy V.; Gollob, Jared; Vaishnaw, Akshay; Simon, Amy; Glanville, Allan R.

doi:10.1016/j.healun.2015.08.012

Cited by 135 publications

(92 citation statements)

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“…Risk stratification based on confirmation of probable/proven LRTI may assist in treatment considerations for HCT recipients with RSV. In addition, several antivirals are in phase 2 trials for treatment of RSV infections in various populations [5,[34][35][36][37], including HCT recipients [7,8], and risk stratification may help develop rational prevention and treatment strategies for immunocompromised patients with these agents.…”

Section: Discussionmentioning

confidence: 99%

“…Respiratory syncytial virus (RSV) infection is associated with significant morbidity and mortality in patients with hematologic malignancy and in hematopoietic cell transplant (HCT) recipients [1,2]. There are no approved treatments for RSV infection in HCT recipients, although several candidates are in development for treatment of RSV infections in various populations [3][4][5][6], including HCT recipients [7,8]. Historically, mortality rates in HCT recipients with lower respiratory tract infection (LRTI) due to RSV have been as high as 55% [9][10][11].…”

mentioning

confidence: 99%

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Supplemental Oxygen–Free Days in Hematopoietic Cell Transplant Recipients With Respiratory Syncytial Virus

Waghmare¹,

Kimball

et al. 2017

The Journal of Infectious Diseases

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Supplemental Oxygen–Free Days in Hematopoietic Cell Transplant Recipients With Respiratory Syncytial Virus

Waghmare¹,

Kimball

et al. 2017

The Journal of Infectious Diseases

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“…117 Similarly, ALN-RSV01 (asvasiran), a small interfering RNA targeting RSV replication, has not progressed due to limited impact on viral parameters and lack of improvement in symptomatic patients. 118,119 ALS-8176 (lumicitabine), an RNA polymerase inhibitor, was associated with a reduction in viral load and clinical severity compared with placebo in a phase II RSV challenge study in healthy adults, 120 although the role of this and other agents awaits clarification in target populations. There are a few investigational agents in phase II study in HCT recipients, namely ALX-0171, a nanobody fusion inhibitor (https://clinicaltrials.gov/ct2/show/NCT03418571 and https://clinicaltrials.gov/ct2/ show/NCT03468829) 1,16 and PC786, a non-nucleoside RSV L protein polymerase inhibitor (https://clinicaltrials.gov/ct2/show/study/NCT03715023).…”

Section: Respiratory Syncytial Virusmentioning

confidence: 99%

Respiratory Virus Infections of the Stem Cell Transplant Recipient and the Hematologic Malignancy Patient

Fontana

Strasfeld

2019

Infectious Disease Clinics of North America

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Respiratory virus infections (RVIs) are increasingly recognized as a cause of significant morbidity and mortality in recipients of hematologic stem cell transplant (HCT) and patients with hematologic malignancy (HM). 1,2 With now widespread use of molecular diagnostics, the epidemiology and spectrum of clinical disease of these infections can be better characterized. Apart from influenza, the currently available antivirals are limited in efficacy and/or associated with potential for toxicity, thus emphasizing the importance of prevention strategies. This article provides a review of the epidemiology, clinical characteristics, management, and prevention of RVIs in HCT recipients and HM patients.No disclosures. KEYWORDS Respiratory virus infection Hematopoietic stem cell transplant RSV Influenza Parainfluenza Human metapneumovirus Rhinovirus Coronavirus KEY POINTSThe morbidity and associated complications of respiratory virus infections are greater in hematopoietic stem cell transplant recipients and patients with hematologic malignancy than in immunocompetent individuals, with severity of illness related to the degree of immunosuppression. Molecular microbiologic testing is the gold standard for diagnosis, allowing differentiation of what are largely overlapping clinical syndromes. Most of the respiratory viruses, apart from influenza and in some circumstances respiratory syncytial virus and adenovirus, are managed supportively. Prevention is key and should focus on vaccination for influenza, avoidance of ill contacts, and compliance with principles of infection control.Infect Dis Clin N Am 33 (2019) 523-544 a Studies are a combination of PCR and traditional laboratory methods (eg, culture, direct fluorescent antibody, and enzyme immunoassay). b PCR-based studies. c Includes all-cause and attributable mortality with variable timeframe to death. d One mortality in a coinfected patient attributed to enterovirus/rhinovirus infection.

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“…ALN-RSV01, a small interfering RNA, was effective in a challenge model 123 and reduced cumulative daily symptom scores and incidence of progressive bronchiolitis obliterans syndrome in lung transplant recipients. 124,125 There is currently no ongoing clinical development.…”

Section: Aln-rsv01mentioning

confidence: 99%

Antiviral Treatments

Ison

2017

Clinics in Chest Medicine

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Most viral respiratory tract infections are caused by classic respiratory viruses, including influenza, respiratory syncytial virus, human metapneumovirus, parainfluenza, rhinovirus, and adenovirus, whereas other viruses, such as herpes simplex, cytomegalovirus, and measles virus, can opportunistically affect the respiratory tract. The M2 inhibitors, amantadine and rimantadine, were historically effective for the prevention and treatment of influenza A but all circulating strains are currently resistant to these drugs. Neuraminidase inhibitors are the sole approved class of antivirals to treat influenza. Ribavirin, especially when combined with intravenous antibody, reduces morbidity and mortality among immunosuppressed patients.

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

Cited by 135 publications

References 30 publications

Supplemental Oxygen–Free Days in Hematopoietic Cell Transplant Recipients With Respiratory Syncytial Virus

Supplemental Oxygen–Free Days in Hematopoietic Cell Transplant Recipients With Respiratory Syncytial Virus

Respiratory Virus Infections of the Stem Cell Transplant Recipient and the Hematologic Malignancy Patient

Antiviral Treatments

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