Macugen (pegaptanib sodium injection) Dermatology and Ophthalmology Advisory Dermatology and Ophthalmology Advisory Committee Meeting Committee Meeting Rockville, Maryland Rockville, Maryland August 27, 2004 August 27, 2004 Center for Drug Evaluation and Research Center for Drug Evaluation and Research
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Macugen (pegaptanib sodium injection) Dermatology and Ophthalmology Advisory Committee Meeting Rockville, Maryland August 27, 2004 Dermatology and Ophthalmology.
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mediators– Endophthalmitis never previously seen in vehicle group
• Sham, reluctantly acceptable– Require multiple other doses in addition to sham– Increased chance of bias influencing results
15Dermatology and Ophthalmology Advisory Committee Dermatology and Ophthalmology Advisory Committee August 27, 2004August 27, 2004
Dose RangingDose RangingDose RangingDose Ranging
• Multiple Doses– Prefer to include a dose higher in
concentration than the “best” dose
– Prefer to include a dose lower in concentration than the “best” dose
• Multiple Doses– Prefer to include a dose higher in
concentration than the “best” dose
– Prefer to include a dose lower in concentration than the “best” dose
16Dermatology and Ophthalmology Advisory Committee Dermatology and Ophthalmology Advisory Committee August 27, 2004August 27, 2004
EfficacyEfficacyEfficacyEfficacy
• Statistical significance and clinical relevance in visual function at more than one time point
– Visual acuity– Visual field– Color vision
• Statistical significance and clinical relevance in visual function at more than one time point
– Visual acuity– Visual field– Color vision
17Dermatology and Ophthalmology Advisory Committee Dermatology and Ophthalmology Advisory Committee August 27, 2004August 27, 2004
EvaluationsEvaluationsEvaluationsEvaluations
• Best corrected distance visual acuity*– ETDRS equivalent at 4 meters
• Dilated seven field fundus photographs• Fluorescein or indocyanine green angiography• Dilated ophthalmoscopy*• Dilated slit lamp exam *• Endothelial cell count**• Systemic clinical and laboratory evaluation*** Every visit** Beginning and end of at least one study
• Best corrected distance visual acuity*– ETDRS equivalent at 4 meters
• Dilated seven field fundus photographs• Fluorescein or indocyanine green angiography• Dilated ophthalmoscopy*• Dilated slit lamp exam *• Endothelial cell count**• Systemic clinical and laboratory evaluation*** Every visit** Beginning and end of at least one study
18Dermatology and Ophthalmology Advisory Committee Dermatology and Ophthalmology Advisory Committee August 27, 2004August 27, 2004
Two versus Four MetersTwo versus Four MetersTwo versus Four MetersTwo versus Four Meters
• Four meters is the standard– Ophthalmology 1996; 103:181-182
• At distances shorter than 4 meters:– Leaning can affect the number of line read
• At 2 meters – ~17 inches equals 1 line of acuity
– ETDRS showed poor reliability at 1 meter compared to 4 meters
– More significant if a feature of treatment or an adverse event can lead to unmasking of treatment
• Four meters is the standard– Ophthalmology 1996; 103:181-182
• At distances shorter than 4 meters:– Leaning can affect the number of line read
• At 2 meters – ~17 inches equals 1 line of acuity
– ETDRS showed poor reliability at 1 meter compared to 4 meters
– More significant if a feature of treatment or an adverse event can lead to unmasking of treatment
19Dermatology and Ophthalmology Advisory Committee Dermatology and Ophthalmology Advisory Committee August 27, 2004August 27, 2004
Recommended EndpointsRecommended EndpointsPercentage of Patients withPercentage of Patients with
Recommended EndpointsRecommended EndpointsPercentage of Patients withPercentage of Patients with
• Doubling of the visual angle– 15 or more letters on ETDRS chart at 4 meters
• Halving of the visual angle– 15 or more letters on ETDRS chart at 4 meters
• Quadrupling of the visual angle– 30 or more letters on ETDRS chart at 4 meters
• Doubling of the visual angle– 15 or more letters on ETDRS chart at 4 meters
• Halving of the visual angle– 15 or more letters on ETDRS chart at 4 meters
• Quadrupling of the visual angle– 30 or more letters on ETDRS chart at 4 meters
20Dermatology and Ophthalmology Advisory Committee Dermatology and Ophthalmology Advisory Committee August 27, 2004August 27, 2004
Recommended Endpoints (2)Recommended Endpoints (2)Difference in Group MeanDifference in Group Mean
Recommended Endpoints (2)Recommended Endpoints (2)Difference in Group MeanDifference in Group Mean
• Statistically significant difference between groups in mean visual acuity of 15 or more letters
• Statistically significant difference between groups in mean visual acuity of 15 or more letters
21Dermatology and Ophthalmology Advisory Committee Dermatology and Ophthalmology Advisory Committee August 27, 2004August 27, 2004