文档介绍：Tysabri®(natalizumab) BiogenIdecInc. BLA125104/15
PeripheralandCentralNervousSystem
DrugsAdvisoryCommittee
GaithersburTysabri®(natalizumab) BiogenIdecInc. BLA125104/15
PeripheralandCentralNervousSystem
DrugsAdvisoryCommittee
Gaithersburg,Maryland
March7-8,2006
AliceHughes,.
DivisionofNeurologyProducts
CenterforDrugEvaluationandResearch
1
ReviewofNon-PMLSafetyIssues
2
Outline
InfectionsotherthanPML
Immunogenicityandhypersensitivityreactions
Carcinogenicity
Post-marketingreportsofseriousadverseevents
Summaryofmajorsafetyconcerns
3
Natalizumab-andplacebo-treatedpatientshadsimilarincidencesof:
infectionsoverall:%%()
seriousinfections:%%
Natalizumab-andplacebo-treatedpatientshadsimilarincidencesof:
upperrespiratorytractinfections:%%
UTIs:%%
seriousUTIs:%%
gastroenteritis:%%
InfectionsotherthanPML: Placebo-controlledMSstudies
4
InfectionsotherthanPML: MSstudies
Incidencesofspecificinfectionsinplacebo-controlledstudies:
alllowerrespiratorytractinfections:%%()
seriouspneumonias:%%
vaginalinfections:%%
allherpesinfections:%%
gingivalinfections:%%
Atypicalinfections
cryptosporidialgastroenteritiswithprolongedcourse(inmonotherapyStudy1801)
acuteCMVinfectionwithtransaminitis(inopen-labelStudy1808)
5
InfectionsotherthanPML: Placebo-controlledCDstudies
Incidenceofinfectionsoverall:
%%()
Incidenceofseriousinfections:
%%
Incidencesofselectedinfections:
URIs:27%%
UTIs:%%
vaginalinfections:%%
allherpesinfections:%%
perianalabcesses:%%
seriousviralmeningitides:%(2)
seriousUTIs:%(2)
OneseriousCMVinfection(CMVcolitis)
Patientalsoreceivingazathioprine
6
InfectionsotherthanPML: Long-termCDstudies
AtypicalInfections
Sixseriousatypicallowerrespiratorytractinfections
Pneumoniawithlungabscess
Pulmonaryaspergillosis
P