Activity of oral ALS-008176 in a respiratory syncytial virus challenge study

New England Journal of Medicine

Volumn 373, Issue 21, 2015, Pages 2048-2058

  De Vincenzo, John P ^a   McClure, Matthew W ^b   Symons, Julian A ^b   Fathi, Hosnieh ^c   Westland, Christopher ^b   Chanda, Sushmita ^b   Lambkin Williams, Rob ^c   Smith, Patrick ^d   Zhang, Qingling ^e   Beigelman, Leo ^b   Blatt, Lawrence M ^b   Fry, John ^b  

^a UNIVERSITY OF TENNESSEE COLLEGE OF MEDICINE   (United States)

^b AliosBiopharma   (United States)

^c Retroscreen Virology   (United Kingdom)

^d D3 Medicine LLC   (United States)

^e UNIVERSITY AT BUFFALO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; ALS 008176; ASPARTATE AMINOTRANSFERASE; CREATINE KINASE; NUCLEOSIDE DERIVATIVE; PLACEBO; UNCLASSIFIED DRUG; 4'-CHLOROMETHYL-2'-DEOXY-3',5'-DI-O-ISOBUTYRYL-2'-FLUOROCYTIDINE; ANTIVIRUS AGENT; DEOXYCYTIDINE;

ADULT; ADVERSE OUTCOME; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANTIVIRAL ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; COUGHING; DISEASE SEVERITY; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG HALF LIFE; DRUG SAFETY; EPISTAXIS; FEMALE; HUMAN; HUMAN EXPERIMENT; HUMAN RESPIRATORY SYNCYTIAL VIRUS; INOCULATION; LIMIT OF QUANTITATION; LOADING DRUG DOSE; MALE; MAXIMUM PLASMA CONCENTRATION; MORBIDITY; MORTALITY; NORMAL HUMAN; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RESPIRATORY SYNCYTIAL VIRUS INFECTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SEQUENCE ANALYSIS; STEADY STATE; THROMBOCYTE COUNT; TIME TO MAXIMUM PLASMA CONCENTRATION; UPPER RESPIRATORY TRACT INFECTION; VIRAL CLEARANCE; VIRUS LOAD; VIRUS RESISTANCE; ADOLESCENT; ANALOGS AND DERIVATIVES; CLINICAL TRIAL; DRUG EFFECTS; ISOLATION AND PURIFICATION; MIDDLE AGED; MUCUS; MULTICENTER STUDY; ORAL DRUG ADMINISTRATION; PHYSIOLOGY; RESPIRATORY SYNCYTIAL VIRUS INFECTIONS; VIROLOGY; VIRUS REPLICATION; YOUNG ADULT;

ADMINISTRATION, ORAL; ADOLESCENT; ADULT; ANTIVIRAL AGENTS; AREA UNDER CURVE; DEOXYCYTIDINE; DOUBLE-BLIND METHOD; FEMALE; HUMANS; MALE; MIDDLE AGED; MUCUS; RESPIRATORY SYNCYTIAL VIRUS INFECTIONS; RESPIRATORY SYNCYTIAL VIRUSES; VIRAL LOAD; VIRUS REPLICATION; YOUNG ADULT;

EID: 84947719880     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMoa1413275     Document Type: Article

References (27)

1. Nair H, Nokes DJ, Gessner BD, et al. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet 2010;375:1545-55.
2. Hall CB, Weinberg GA, Iwane MK, et al. The burden of respiratory syncytial virus infection in young children. N Engl J Med 2009;360:588-98.
3. Leader S, Kohlhase K. Recent trends in severe respiratory syncytial virus (RSV) among US infants, 1997 to 2000. J Pediatr 2003; 143: Suppl: S127-S132.
4. Thompson WW, Shay DK, Weintraub E, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 2003; 289: 179-86.
5. Falsey AR, Hennessey PA, Formica MA, Cox C, Walsh EE. Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med 2005; 352: 1749-59.
6. Lee N, Lui GC, Wong KT, et al. High morbidity and mortality in adults hospitalized for respiratory syncytial virus infections. Clin Infect Dis 2013; 57: 1069-77.
7. Widmer K, Zhu Y, Williams J V, Griffin MR, Edwards KM, Talbot HK. Rates of hospitalizations for respiratory syncytial virus, human metapneumovirus, and influenza virus in older adults. J Infect Dis 2012;206:56-62.
8. Ventre K, Randolph AG. Ribavirin for respiratory syncytial virus infection of the lower respiratory tract in infants and young children. Cochrane Database Syst Rev 2007; 1: CD000181.
9. American Academy of Pediatrics Committee on Infectious Diseases, American Academy of Pediatrics Bronchiolitis Guidelines Committee. Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics 2014; 134: 415-20.
10. American Academy of Pediatrics Committee on Infectious Diseases, American Academy of Pediatrics Bronchiolitis Guidelines Committee. Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics 2014; 134(2): e620-e638.
11. Buckingham SC, Bush AJ, Devincenzo JP. Nasal quantity of respiratory syncyti-cal virus correlates with disease severity in hospitalized infants. Pediatr Infect Dis J 2000;19:113-7.
12. DeVincenzo JP, El Saleeby CM, Bush AJ. Respiratory syncytial virus load predicts disease severity in previously healthy infants. J Infect Dis 2005; 191: 1861-8.
13. El Saleeby CM, Bush AJ, Harrison LM, Aitken JA, Devincenzo JP. Respiratory syncytial virus load, viral dynamics, and disease severity in previously healthy naturally infected children. J Infect Dis 2011; 204: 996-1002.
14. DeVincenzo JP, Wilkinson T, Vaish-naw A, et al. Viral load drives disease in humans experimentally infected with respiratory syncytial virus. Am J Respir Crit Care Med 2010;182:1305-14.
15. DeVincenzo J, Lambkin-Williams R, Wilkinson T, et al. A randomized, doubleblind, placebo-controlled study of an RNAi-based therapy directed against respiratory syncytial virus. Proc Natl Acad Sci USA 2010; 107: 8800-5.
16. Kim YI, DeVincenzo JP, Jones BG, et al. Respiratory syncytial virus human experimental infection model: provenance, production, and sequence of low-passaged memphis-37 challenge virus. PLoS One 2014;9(11):e113100.
17. DeVincenzo JP, Whitley RJ, Mackman RL, et al. Oral GS-5806 activity in a respiratory syncytial virus challenge study. N Engl J Med 2014;371:711-22.
18. Perkins SM, Webb DL, Torrance SA, et al. Comparison of a real-time reverse transcriptase PCR assay and a culture technique for quantitative assessment of viral load in children naturally infected with respiratory syncytial virus. J Clin Micro-biol 2005;43:2356-62.
19. Johnson S, Griego SD, Pfarr DS, et al. A direct comparison of the activities of two humanized respiratory syncytial virus monoclonal antibodies: MEDI-493 and RSHZl9. J Infect Dis 1999; 180: 35-40.
20. Johnson S, Oliver C, Prince GA, et al. Development of a humanized monoclonal antibody (MEDI-493) with potent in vitro and in vivo activity against respiratory syncytial virus. J Infect Dis 1997; 176: 1215-24.
21. Wu H, Pfarr DS, Johnson S, et al. Development of motavizumab, an ultra-potent antibody for the prevention of respiratory syncytial virus infection in the upper and lower respiratory tract. J Mol Biol 2007;368:652-65.
22. Douglas JL, Panis ML, Ho E, et al. Small molecules VP-14637 and JNJ-2408068 inhibit respiratory syncytial virus fusion by similar mechanisms. Antimi-crob Agents Chemother 2005; 49: 2460-6.
23. McCown MF, Rajyaguru S, Le Pogam S, et al. The hepatitis C virus replicon presents a higher barrier to resistance to nucleoside analogs than to nonnucleoside polymerase or protease inhibitors. Antimicrob Agents Chemother 2008; 52: 1604-12.
24. Zoulim F. Hepatitis B virus resistance to antiviral drugs: where are we going? Liver Int 2011;31:Suppl 1:111-6.
25. Lundin A, Bergström T, Bendrioua L, Kann N, Adamiak B, Trybala E. Two novel fusion inhibitors of human respiratory syncytial virus. Antiviral Res 2010; 88: 317-24.
26. Yan D, Lee S, Thakkar VD, Luo M, Moore ML, Plemper RK. Cross-resistance mechanism of respiratory syncytial virus against structurally diverse entry inhibitors. Proc Natl Acad Sci USA 2014; 111(33):E3441-E3449.
27. Grad YH, Newman R, Zody M, et al. Within-host whole-genome deep sequencing and diversity analysis of human respiratory syncytial virus infection reveals dynamics of genomic diversity in the absence and presence of immune pressure. J Virol 2014;88:7286-93.