For the PSV-FAI-001 Study Investigators

Transcription

1 An Injectable Fluocinolone Acetonide Insert Decreases the Incidence of Recurrence in Patients with Chronic Non-infectious Uveitis Affecting the Posterior Segment of the Eye: 12 Month Results Glenn J. Jaffe, MD, Duke University Dario A. Paggiarino, MD, psivida Corp. Gerard E. Riedel, PhD, psivida Corp. For the PSV-FAI-001 Study Investigators

2 Disclosures Glenn J. Jaffe, MD AbbVie Consultant Dario A. Paggiarino, MD psivida Corp., Employee Gerard E. Riedel, PhD psivida Corp. Employee

3 Purpose Efficacy and safety of an injectable FAi delivering microdoses for 36 months after a single administration in patients with chronic non-infectious posterior segment uveitis

4 Rationale Uveitis chronic disease Requires long-term Rx Sustained release useful approach May require surgical insertion May have limited effect duration? Office based long-term delivery feasible

5 Methods

6 Design Prospective, randomized Sham-controlled, double masked Phase III trial 6 countries 33 sites

7 Patients Uveitis Duration >1 yr Required repeated steroid injections, PO steroids or IMT for recurrence IOP>21, or IOP rx excluded Received FAi:sham 2:1 Analysis time points 6,12,36 months

8 Outcome Measures Efficacy Primary Endpoint: 6mo study eye recurrence Exploratory endpoints 12, 36 mo study eye recurrence proportion Fellow eye recurrence proportion #,time to recurrence BCVA change Adjunctive treatments ME resolution

9 Outcome Measures Safety Ocular AEs Non-ocular AEs

10 Injectable Sustained Released Fluocinolone Acetonide Polyimide tube Fluocinolone acetonide core 0.18 mg 3.5 mm in length Modified 25 g needle injector Release up to 3 years

11 Technique

12 Technique

13 Technique

14 12 MONTH RESULTS

15 Patients 129 eyes of 129 patients 87 FAi, 42 sham

16 Enrollment Total subjects screened: 171 Screen failures: 42 Randomized: 129 First subject enrolled: 08AUG2013 Last subject enrolled: 30MAR India EMEA US 0 Enrollment

17 Baseline Characteristics Duration of Disease FAi: 7.8 yrs sham: 5.6 yrs BCVA letters FAi: 66.9 sham: 64.9 Vit haze 0/0.5+ FAi: 55.2% sham: 50.0% Vit haze 1/+2 FAi: 44.8% sham: 50.0%

18 Baseline Characteristics Duration of Disease FAi: 7.8 yrs sham: 5.6 yrs BCVA letters FAi: 66.9 sham: 64.9 Vit haze 0/0.5+ FAi: 55.2% sham: 50.0% Vit haze 1/+2 FAi: 44.8% sham: 50.0%

19 Baseline Characteristics Duration of Disease FAi: 7.8 yrs sham: 5.6 yrs BCVA letters FAi: 66.9 sham: 64.9 Vit haze 0/0.5+ FAi: 55.2% sham: 50.0% Vit haze 1/+2 FAi: 44.8% sham: 50.0%

20 Baseline Characteristics Duration of Disease FAi: 7.8 yrs sham: 5.6 yrs BCVA letters FAi: 66.9 sham: 64.9 Vit haze 0/0.5+ FAi: 55.2% sham: 50.0% Vit haze 1/+2 FAi: 44.8% sham: 50.0%

21 Results Recurrence Rate at 12 Months ITT population FAi Sham P Value (Odd Ratio/CI) US Criteria ROW Criteria 27.6% 85.7% 37.9% 97.6% P< CI 5.89, P< CI

22 Results Recurrence Rate at 12 Months ITT population FAi Sham P Value (Odd Ratio/CI) US Criteria ROW Criteria 27.6% 85.7% 37.9% 97.6% P< CI 5.89, P< CI

23 Results Recurrence Rate at 12 Months PP population FAi Sham P Value (Odd Ratio/CI) US Criteria ROW Criteria 6.5% 60% 5.7% 92.3% P< CI 5.12, P< CI 19.09,

24 Results Recurrence Rate at 12 Months PP population FAi Sham P Value (Odd Ratio/CI) US Criteria ROW Criteria 6.5% 60% 5.7% 92.3% P< CI 5.12, P< CI 19.09,

25 Probability of Recurrence (US Criteria) ITT Population ITT PP PP Population

26 Results Recurrence Rate Sig. differences regardless of: Region Systemic Rx Gender Uveitis duration Lens status

27 Use of Adjunctive Therapies by 12 months Therapy FAi Sham Systemic steroids or immunosuppressants 19.5% 40.5% Intra-periocular steroids 6.9% 61.9% Topical steroids 20.7% 47.6%

28 Use of Adjunctive Therapies by 12 months Therapy FAi Sham Systemic steroids or immunosuppressants 19.5% 40.5% Intra-periocular steroids 6.9% 61.9% Topical steroids 20.7% 47.6%

29 Use of Adjunctive Therapies by 12 months Therapy FAi Sham Systemic steroids or immunosuppressants 19.5% 40.5% Intra-periocular steroids 6.9% 61.9% Topical steroids 20.7% 47.6%

30 Proportion receiving systemic treatment at month 12 (percent) Systemic Rx at Month p = % (11/20) % (0/42) p = 0.3 No systemic treatment at enrollment (N=62) 5.0% (1/20) FAi Sham 15.9% (7/44) systemic corticosteroid or immunosuppressant at enrollment (N=64)

31 Mean BCVA letter change at month 12 vs baseline BCVA at Month 12: ITT 10 p = letters (n=85) letters (n=39) 0 FAi overall Sham

32 Mean BCVA letter change at month 12 vs baseline BCVA at Month 12: PP 10 p = letters (n=53) letters (n=11) 0 FAi overall Sham

33 Proportion with BCVA gain of 15 or more letters (percent) BCVA gain: ITT BCVA gain of > 15 letters: study eye p = BCVA gain (>/=15 ltr) at month 12 FAi Sham

34 Proportion with BCVA loss of 15 or more letters (percent) BCVA loss: ITT BCVA loss of > 15 letters: study eye p = BCVA loss (>/=15 ltr) at month 12 FAi Sham

35 Proportion with BCVA loss of 15 or more letters (percent) BCVA loss: PP BCVA loss of > 15 letters: study eye p < BCVA loss (>/=15 ltr) at month 12 FAi Sham

36 Results Safety

37 Ocular TEAEs (study eye) Eye disorders AE with incidence > 5% in either treatment group FAi (N=87) Percentage of Subjects Sham (N=42) Cataract Visual acuity reduced Foreign body sensation Conjunctival hemorrhage Cystoid macular edema Eye pain Macular edema Uveitis Vitreous floaters Vitreous opacities Investigations IOP increased

38 Ocular TEAEs (study eye) Eye disorders AE with incidence > 5% in either treatment group FAi (N=87) Percentage of Subjects Sham (N=42) Cataract Visual acuity reduced Foreign body sensation Conjunctival hemorrhage Cystoid macular edema Eye pain Macular edema Uveitis Vitreous floaters Vitreous opacities Investigations IOP increased

39 Results 12-month IOP FAi Sham Baseline months Change

40 FAi 29.9% Sham 23.8% Results IOP >21 on >1 visit

41 IOP-lowering Medication (study eye) Interval Percentage of Subjects requiring IOP-lowering medication FAi (N=87) Sham (N=42) Day 1 through month Month 3 through month Month 6 through month Month 9 through month Cumulative through month

42 FAi 3.4% Sham 2.4% Results Filtration IOP Surgery

43 Cataract surgery (study eye) FAi (N=87) Subjects Sham (N=42) Phakic eyes (at study entry) Subjects with cataract surgery from day 1 through month (33.3%) 1 (4.8%)

44 Other FAi Sham Endophthalmitis 0% 4.2% RD 1.1% 2.1%

45 Conclusions Office-based procedure feasible Long-term disease control Significantly decreased recurrences Fewer eyes lost VA Decreased adjunctive Rx Acceptable safety profile Promising approach