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NDA22-291PROMACTA?(Eltrombopag)FDAReviewAndrewDmytrijuk,MD1
ProposedIndication Eltrombopagisindicatedfortheshort-termtreatmentofpreviously-treatedpatientswithchronicidiopathicthrombocytopenicpurpura(ITP)toincreaseplateletcountsandreduceorpreventbleeding.Underlinesaddedforemphasis2
EltrombopagBackgroundTablet,administereddailyBindstotransmembraneportionofTPO receptorPreclinicaltestingofEltrombopag:stimulatedplateletsonlyinchimpanzeesinotheranimals(inhighdoses):ChronicprogressivenephropathyLiverabnormalitiesCataractsPreclinicaltestingofanotherTPO receptoragonist:marrowfibrosis3
ClinicalDatabase
Eltrombopag(E)exposuren=1088ChronicITP:n=330ThrombocytopeniainhepatitisC:n=56Chemotherapy-inducedthrombocytopenia:n=134Clinicalpharmacology:N=5684
ITPProgram“Shortterm”:6weekexposure-Completed:placebocontrolled -773A -773B-On-going,singlearm:“REPEAT” “Longterm”:≥6monthexposure-On-going:placebocontrolled:“RAISE”-On-going:singlearm:“EXTEND”5
MajorReviewTopics:“ShortTerm”Efficacy:increaseplateletcountsreduceorpreventbleedingSafety:bleedingrisksfollowingdrugdiscontinuationhepatotoxicity“shortterm”indicationbutlongtermusage -morehepatotoxicity? -potentialmarrowfibrosis?6
DataPresentationCompletedstudies(short-term):773A773BOn-goingstudies/interim:REPEAT(cyclesofshort-term)EXTENDRAISE7
“ShortTerm”Rationale:
Protocols “ShorttermtreatmentmayincreaseplateletcountsinpatientswithchronicITPscheduledforsurgicalordentalprocedures,wherealowplateletcountcanbeahindranceorevenprohibitiveoftheprocedureduetotheriskofexcessivebleeding.”Underlinesaddedforemphasis8
Studies773Aand773B:DesignFeaturesDB,PC,multi-nationalEligibility:-platelets30Kdespiteatleast1priortherapy-didnotselectpatientsscheduledforproceduresRandomization:-773A:placebooractivedrugat
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