approved products for the treatment of cmv retinitis in immunocompromised patients william m. boyd,...
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![Page 1: Approved Products for the Treatment of CMV Retinitis in Immunocompromised Patients William M. Boyd, M.D. Division of Anti-inflammatory, Analgesic, and](https://reader036.vdocument.in/reader036/viewer/2022062516/56649dc45503460f94ab6c6c/html5/thumbnails/1.jpg)
Approved Products for the Treatment of CMV Retinitis in Immunocompromised Patients
William M. Boyd, M.D.Division of Anti-inflammatory, Analgesic, and
Ophthalmologic Drug Products
HFD-550
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Approved Products
• Cytovene-IV (ganciclovir)
• Foscavir Injection (foscarnet)
• Cytovene Capsules (ganciclovir)
• Vitrasert Implant (ganciclovir)
• Vistide Injection (cidofovir)
• Vitravene for Injection (fomvirsen)
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Cytovene-IV (ganciclovir)
• Approved June 23, 1989
• Clinical Data Source(s) for Approval– Study #1 - randomized, controlled trial,
immediate versus delayed treatment (N = 42)– Study #2 - nonrandomized, retrospective,
immediate versus delayed treatment (N = 41)
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Cytovene-IV (ganciclovir)
• Primary Endpoints for Study #1 and #2:– Time to progression of CMV retinitis
• Primary Endpoint Analysis– Study #1 (photos): median time to progression
of 50 days for immediate treatment; 14 days for delayed
– Study #2 (exam): median time to progression of 71 days for immediate treatment; 29 days for delayed
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Foscavir Injection (foscarnet)
• Approved September 27, 1991
• Clinical Data Source(s) for Approval– randomized, open label, controlled trial,
immediate versus delayed treatment (N = 24)
• Primary Endpoint– Time to progression of CMV retinitis
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Foscavir Injection (foscarnet)
• Primary Endpoint Analysis– median time to progression of 93 days for
immediate treatment; 22 days for delayed (photos)
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Cytovene Capsules (ganciclovir)
• Approved December 22, 1994
• Not approved for induction due to poor bioavailability (5% available)
• Study Design for Maintenance Indication– three randomized, open label trials with
Cytovene-IV as comparator (N total = 505)
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Vitrasert Implant (ganciclovir)
• Approved March 4, 1996
• Clinical Data Source(s) for Approval– randomized, parallel, ganciclovir implant
versus ganciclovir IV (N =188)
• Primary Endpoint– Time to progression of CMV retinitis
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Vitrasert Implant (ganciclovir)
• Primary Endpoint Analysis– median time to progression of 210 days for
immediate treatment; 120 days for delayed (photos)
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Vistide Injection (cidofovir)
• Approved June 26, 1996
• Clinical Data Source(s) for Approval– randomized, open label, controlled trial,
immediate versus delayed treatment (N = 48)
• Primary Endpoint– Time to progression of CMV retinitis
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Vistide Injection (cidofovir)• Primary Endpoint Analysis
– median time to progression of 120 days for immediate treatment; 22 days for delayed (photos)
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Vitravene for Injection (fomvirsen)
• Approved August 26, 1998
• Clinical Data Source(s) for Approval– limited, open label, controlled clinical studies,
immediate versus delayed treatment
(N = 80 eyes)
• Primary Endpoint– Time to progression of CMV retinitis
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Vitravene for Injection (fomvirsen)
• Primary Endpoint Analysis– median time to progression of 80 days for
immediate treatment; 14 days for delayed (photos)
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Approved Products
Product Administration
Cytovene-IV IVFoscavir Injection IVCytovene Capsules OralVitrasert Implant Intraocular implantVistide Injection IVVitravene for Injection Intravitreal injection
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Approved Products for the Treatment of CMV Retinitis in Immunocompromised Patients
William M. Boyd, M.D.Division of Anti-inflammatory, Analgesic, and
Ophthalmologic Drug Products
HFD-550
![Page 16: Approved Products for the Treatment of CMV Retinitis in Immunocompromised Patients William M. Boyd, M.D. Division of Anti-inflammatory, Analgesic, and](https://reader036.vdocument.in/reader036/viewer/2022062516/56649dc45503460f94ab6c6c/html5/thumbnails/16.jpg)
Valcyt 450 mg Tablets (valganciclovir hydrochloride)
NDA 21-304
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valganciclovir tablets
• NDA submitted September 28, 2000
• Clinical Data Source(s) for Approval– randomized, open label, parallel group,
valganciclovir versus ganciclovir IV (N=160)
• Primary Endpoint– proportion of patients with disease progression
at week 4
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valganciclovir tablets
• Primary Endpoint Analysis– 7 subjects in valganciclovir arm and 7 subjects
in the ganciclovir treatment arm had CMV progression at week 4 (photos)
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valganciclovir tabletsAnalysis of CMV Retinitis Progression by Week 4
Compared to Baseline(Medical Officer’s Masked Photographic Assessment)
GCV/VGCVN=80
VGCV/VGCVN=80
Non-progressor 64 (80%) 64 (80%)Progressor 7 (9%) 7 (9%)
Unevaluable*
*Unevaluable = “missing,” “cannotgrade,” or “no CMV at baseline”
9 (11%) 9 (11%)
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valganciclovir tablets
Unevaluable subjects GCV/VGCV VGCV/VGCV
No photographicevidence of CMV
retinitis at Baseline
3 2
Missing photos 4 6
Inadequatephotographic quality
2 1
Total 9 9
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valganciclovir tabletsMedical Officer’s Assessment
GCV/VGCVN=80
VGCV/VGCVN=80
Non-progressor 64 (80%) 64 (80%)Progressor 7 (9%) 7 (9%)
Unevaluable 9 (11%) 9 (11%)
Applicant/Reading Center Assessment
GCV/VGCVN=80
VGCV/VGCVN=80
Non-progressor 63 (79%) 64 (80%)Progressor 7 (9%) 7 (9%)
Unevaluable 10 (13%) 9 (11%)