DISCOVER RESULTS FROM PIVOTAL TRIAL AND GPS:

GPS OPEN-LABEL STUDY ON XEN® GEL STENT VS TRABECULECTOMY

Pivotal trial

Results of a prospective, multicenter, single-arm, open-label, US clinical trial to evaluate the safety and effectiveness of the XEN® Gel Stent in refractory glaucoma subjects (N = 65) where previous filtering or cilioablative procedures failed, or IOP was unresponsive to maximum tolerated medication. Medication washout was not performed; all IOP-lowering medications were discontinued on the day of surgery.1

Study eyes undergoing glaucoma-related secondary surgical intervention (SSI) and/or removal of the XEN® Gel Stent prior to the 12-month evaluation were considered to be nonresponders. Seven subjects in the study underwent needling procedures with mitomycin C; 4 of these subjects were considered responders.1

*76.3% (95% CI = 65.8%, 86.8%); using observed data and failures for subjects with glaucoma-related SSI and multiple imputations for missing data (N = 65).
†Patients who completed the 12-month visit (n = 52).

Pivotal study most common AEs

The most common postoperative AEs included BCVA loss of ≥ 2 lines (≤ 30 days 15.4%; > 30 days 10.8%; 12 months 6.2%), hypotony IOP < 6 mm Hg at any time (24.6%), IOP increase ≥ 10 mm Hg from baseline (21.5%), and needling procedure (32.3%).1

‡No clinically significant consequences were associated with hypotony, such as choroidal effusions, suprachoroidal hemorrhage, or hypotony maculopathy. IOP < 6 mm Hg was defined as an adverse event, regardless of whether there were any associated complications or sequelae related to the low pressure. Thirteen cases occurred at the 1-day visit; there were no cases of persistent hypotony, and no surgical intervention was required for any case of hypotony.1

 

See additional pivotal trial data

GPS design
An additional open-label study

Study objective14

  • To compare effectiveness and safety of XEN® Gel Stent to trabeculectomy in refractory glaucoma patients poorly controlled on ≥ 1 topical IOP-lowering medication

Methodology14

  • Randomized, prospective, parallel-group, open-label, multicenter study in 158 eyes
  • Enrolled patients had glaucoma with medicated IOP of 15 to 44 mm Hg on ≥ 1 topical IOP-lowering medication

Gps data

  • One eye per patient was randomized 2:1 to XEN® Gel Stent implantation or trabeculectomy at the site level
  • Mitomycin C (MMC) 40 μg (subconjunctival injection) was used intraoperatively in both procedures*

*The XEN® Directions for Use (DFU) discusses sponge administration of MMC, an antifibrotic therapy, to the surgical site.1 Administration of MMC/antifibrotic therapy by injection is not approved in the United States.

GPS = Gold Standard Pathway Study.

PATIENT CHARACTERISTICS14

aHispanic patients have been previously presented as American Indian/Alaska Native (following the Clinical Data Interchange Standards Consortium control terminology tabulation model).

bStudy eye.

cIncluded laser procedures and surgeries (surgeries included cycloablation, minimally invasive surgery, and trabeculectomy).

GPS primary endpoint

Primary effectiveness endpoint14

A composite endpoint of patients (%) achieving the following at the 12-month visit:

  • ≥ 20% IOP reduction from baseline
  • Without increase in topical IOP-lowering medication
  • Without clinical hypotony (IOP ≤ 6 mm Hg with vision reduction [≥ 2 lines] related to macular changes [macular folds], optic disc edema, and/or serous choroidal detachments)
  • Without vision loss to counting fingers
  • Without secondary surgical intervention (SSI)

aPatients with missing data were considered failures in this analysis.15

  • Noninferiority of the XEN® Gel Stent to trabeculectomy was claimed if the lower limit of the 95% confidence interval was greater than -24%
  • At month 12, XEN® Gel Stent was statistically noninferior to trabeculectomy
  • There was no statistically significant difference between the proportion of patients achieving the primary endpoint in both arms

GPS secondary endpoints

Limitations

All secondary endpoints were prespecified, nonranked endpoints, and were not controlled for multiplicity. Therefore, these secondary endpoints cannot be regarded as statistically significant.

MEAN IOP AND MEAN IOP-LOWERING MEDICATION COUNT OVER TIME14

an = 91 (month 3), 82 (month 6), and 87 (month 12).
 bn = 42 (month 3) and 41 (month 12). Both footnotes refer to the medication count analysis.

med = medication.

  • In the XEN® Gel Stent arm, mean IOP at baseline was 23.1 mm Hg on 2.8 mean medications and 14.4 mm Hg on 0.6 mean medications at month 12
  • In the trabeculectomy arm, mean IOP at baseline was 22.6 mm Hg on 2.5 mean medications and 11.8 mm Hg on 0.3 mean medications at month 12
  • 62.1% (59/95) of eyes were IOP-lowering medication free at 12 months in the XEN® Gel Stent arm vs 70.5% (31/44) in the trabeculectomy arm

Limitations

All secondary endpoints were prespecified, nonranked endpoints, and were not controlled for multiplicity. Therefore, these secondary endpoints cannot be regarded as statistically significant.

MEAN BCVA OVER TIME14

Y-axis values in parentheses correspond to equivalent ETDRS Snellen fraction conversion from logMAR units.16

ETDRS = Early Treatment Diabetic Retinopathy Study; logMAR = logarithm of the minimum angle of resolution.

GPS patient-reported outcomes

PROs UTILIZING THE VALIDATED SYMPTOM AND HEALTH PROBLEM CHECKLIST (SHPC-18)14

  • The 2-domain SHPC-18 questionnaire, developed and validated by the Collaborative Initial Glaucoma Treatment Study (CIGTS) group, was used to measure the frequency and bothersomeness of both local eye symptoms and visual function problems
  • Lower scores represent less frequency and bothersomeness of local eye symptoms and visual function problems
  • Additional PROs evaluating XEN® Gel Stent exist in published literature

Limitations

All secondary endpoints were prespecified, nonranked endpoints, and were not controlled for multiplicity. Therefore, these secondary endpoints cannot be regarded as statistically significant.

LOCAL EYE SYMPTOMS: CHANGE FROM BASELINE14

  • Local eye symptoms include eye irritation/burning or pain, feeling as if something is in eye, droopy eyelids, excessive tearing, skin sensitivity around eyes, and red eyes

Limitations

All secondary endpoints were prespecified, nonranked endpoints, and were not controlled for multiplicity. Therefore, these secondary endpoints cannot be regarded as statistically significant.

VISUAL FUNCTION PROBLEMS: CHANGE FROM BASELINE14

  • Visual function problems include changes in depth perception; visual distortion; dimming of vision; trouble with color vision; blurry vision; and difficulty with distant or near vision, light transition, seeing in dark places, bright lights, and seeing when stepping down

The change from baseline or between-treatment differences (∆; XEN® Gel Stent minus trabeculectomy) were calculated using least squares means for each treatment arm.

PRO = patient reported outcome.

GPS postoperative interventions

POSTOPERATIVE INTERVENTIONS IN OFFICE14

aTwo patients received both MMC and 5-fluorouracil during needling.

bIncluded air injection in the anterior chamber (n = 2), XEN® Gel Stent removal (n = 2), laser iridotomy (n = 2), digital ocular compression (n = 1), goniosynechialysis (n = 1), laser iridoplasty (n = 1), and paracentesis (n = 1) in the XEN® Gel Stent arm, and digital ocular compression (n = 2) and suture removal (n = 3) in the trabeculectomy arm.

NA = not applicable.

  • 34.7% of patients in the XEN® Gel Stent arm and 63.6% of patients in the trabeculectomy arm required an office-based postoperative intervention. After excluding laser suture lysis from the analysis, 40.9% of patients in the trabeculectomy arm required an office-based postoperative intervention
  • The needling rate was 23.2% with the XEN® Gel Stent and 18.2% with trabeculectomy

GPS adverse events

OPERATIVE AND POSTOPERATIVE AEs14

  • Postoperative AEs were reported in 74.7% (71/95) of XEN® Gel Stent patients and 93.2% (41/44) of trabeculectomy patients 

    –The most common postoperative ocular AEs in both treatment arms were visual acuity reduced by ≥ 2 lines, hypotony (IOP < 6 mm Hg), and IOP increased by ≥ 10 mm Hg from baseline

  • Serious ocular AEs were reported in 4.2% (4/95) of patients in the XEN® Gel Stent arm, including endophthalmitis, device extrusion, IOP increased, periorbital cellulitis, and reduced visual acuity (1/95, 1.1% each)
  • Discontinuations due to AEs were reported in 3.2% (3/95) of patients in the XEN® Gel Stent arm, including 2 patients with a serious ocular AE
  • There were no serious ocular AEs or discontinuations in the trabeculectomy arm
  • 97.9% of XEN® Gel Stent patients and 93.2% of trabeculectomy patients had no surgical complications

    –The most common surgical complication was anterior chamber bleeding, reported in 1.1% (1/95) of XEN® Gel Stent patients and 4.5% (2/44) of trabeculectomy patients

aPer the investigator’s slit lamp assessment and the following categories: lens clear, lens opacity present–not significant, and lens opacity present–visually significant.

bBased on visual field changes.

AE = treatment-emergent adverse event.

  • Subsequent surgical interventions were required in 13.7% of XEN® Gel Stent patients and 18.2% of trabeculectomy patients, including bleb revisions (other than needling; 5.3% vs 4.5%), SSIs (7.4% vs 2.3%), and others (4.2% vs 11.4%), respectively