Abstract
Purpose :
Dry eye (DE) is a common condition that can profoundly impact patient (pt) quality of life. Pathogenesis is multifactorial, yet most therapies only address inflammation or tear film instability. Neurosensory abnormalities have been increasingly recognized as a key DE feature. A therapeutic agent targeting this etiology would be of great value as improving nerve health may be critical to restoring ocular homeostasis. This study evaluated the efficacy and safety of rhNGF in pts with DE.
Methods :
This phase 2, randomized, vehicle (VEH)-controlled study enrolled pts ≥18 years with moderate-to-severe DE for ≥6 months. Pts were randomized 1:1:1 to receive the following drops in both eyes for 4 weeks (wks) + 12 wks follow up: 20 μg/mL rhNGF 3x/day (TID), 20 μg/mL rhNGF 2x/day (BID) + VEH 1x/day, or VEH TID. Primary endpoint was change from baseline in Schirmer test I without anesthesia at wk 4. Secondary endpoints included change in Symptom Assessment in Dry Eye (SANDE) scores. Treatment (tx)-emergent adverse events (TEAEs) were assessed throughout the study.
Results :
In total, 261 pts were randomized to rhNGF TID (N=87), rhNGF BID (N=86), or VEH (N=88) arms. In the full analysis set, mean (SD) change from baseline in Schirmer test I at wk 4 was higher in the rhNGF BID than VEH arm (4.0 [8.1] vs 1.7 [5.8] mm, P=0.037). Rates of responders (score >10 mm/5 minutes) at wk 4 were also higher in the rhNGF TID (25.9%) and rhNGF BID (29.3%) arms compared with the VEH (11.9%) arm (P=0.028 and P=0.007, respectively). During follow up, the rhNGF TID arm had significantly greater mean (SD) SANDE score reductions, indicating greater symptom improvement, than the VEH arm at wk 8 (-27.2 [25.8] vs -16.9 [20.4], P=0.006), wk 12 (-27.9 [25.6] vs -16.4 [19.6], P=0.002), and wk 16 (-26.5 [25.7] vs -16.7 [19.7], P=0.008). More pts in the rhNGF arms than VEH arm reported ≥1 ocular TEAE in wks 1-4 (69.4% rhNGF TID, 65.5% rhNGF BID, 13.6% VEH); the most common was eye pain (63.5% rhNGF TID, 46.4% rhNGF BID, 4.5% VEH), which was mild and transient in most pts. No study drug-related serious AEs were reported.
Conclusions :
After 4 wks of tx, rhNGF improved Schirmer test I scores and appeared to have clinically relevant enduring effects, with significantly improved DE symptoms up to 12 wks post-tx completion in the rhNGF TID arm. rhNGF was generally well-tolerated, and most TEAEs were mild.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.