1. 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

2. Approved Products Cytovene-IV (ganciclovir) Foscavir Injection (foscarnet) Cytovene Capsules (ganciclovir) Vitrasert Implant (ganciclovir) Vistide Injection (cidofovir) Vitravene for Injection (fomvirsen)

3. 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)

4. 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

5. 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

6. Foscavir Injection (foscarnet) Primary Endpoint Analysis –median time to progression of 93 days for immediate treatment; 22 days for delayed (photos)

7. 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)

8. 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

9. Vitrasert Implant (ganciclovir) Primary Endpoint Analysis –median time to progression of 210 days for immediate treatment; 120 days for delayed (photos)

10. 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

11. Vistide Injection (cidofovir) Primary Endpoint Analysis –median time to progression of 120 days for immediate treatment; 22 days for delayed (photos)

12. 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

13. Vitravene for Injection (fomvirsen) Primary Endpoint Analysis –median time to progression of 80 days for immediate treatment; 14 days for delayed (photos)

14. Approved Products

15. 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

16. Valcyt 450 mg Tablets (valganciclovir hydrochloride) NDA 21-304

17. 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

18. 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)

19. valganciclovir tablets Analysis of CMV Retinitis Progression by Week 4 Compared to Baseline (Medical Officer’s Masked Photographic Assessment)

20. valganciclovir tablets