Table of Contents
NDA#21-240 Histamine Dihydrochloride
CDER/DODP Review Team
Indication
Outline of FDA Review
Metastatic Melanoma
Prognostic Factors
Regulatory History
Regulatory History
MP-US-M01: Study Design
Statistical Analysis Plan
Statistical Analysis Plan
Statistical Analysis Plan
Review Issue #1
FDA Comments
Median Survival (months): ITT
Hazard Ratio and P-value: ITT
Overall Survival: ITT (Cut-off date: 3/8/00)
Overall Survival: ITT (Cut-off date: 9/8/00)
Overall Survival: ITT (FDA using most recent f/u data)
FDA Comments
FDA Comments
Median Survival (months): Subgroups
Survival in Liver Met Subgroup: N=129 (Cut-off date: 9/8/00)
Survival in No Liver Met Subgroup: N=176 (Cut-off date: 9/8/00)
Survival in Patients with Skin/Node/Lung Only Disease: N=82 (Cut-off date: 9/8/00)
FDA Comments
Secondary endpoint: Response
Difference between FDA’s TTP and the applicant’s
Time to Tumor Progression: FDA Analysis in ITT (N=243)
FDA Comments on Efficacy: ITT
Review Issue #2
FDA Comments
Patient Characteristics in the Liver Subgroup
FDA Comments
Adjusted Survival Analysis of the Liver Subgroup (Cut-off 9/8/00)
FDA Comments
Median Survival (months): Liver Subgroups
FDA Comments
Secondary endpoint: Response in the Liver Subgroup
Time to Tumor Progression: LM Subgroup (N=96)
FDA Comments on Efficacy in the Liver Subgroup
Review Issue #3
PPT Slide
IL-2 Regimen
Histamine/IL-2 Regimen
Compliance with Treatment
MP-US-M01: Safety
Death within 30 Days of Last Dose
Grade 3 Toxicity
Grade 4 Toxicity
Safety from Single Arm Study MA-0103
Safety from Single Arm Study MA-0103
Overall Summary
Overall Summary
Overall Summary
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