Tie2 Activation via VE-PTP Inhibition With Razuprotafib as an Adjunct to Latanoprost in Patients With Open Angle Glaucoma or Ocular Hypertension

Abstract

Purpose: To evaluate the ocular hypotensive efficacy and safety of razuprotafib, a novel Tie2 activator, when used as an adjunct to latanoprost in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT).

Methods: Subjects with OAG or OHT and an unmedicated IOP from ≥22 mm Hg to <36 mm Hg were randomized to one of three treatment arms: razuprotafib every day (QD) + latanoprost; razuprotafib twice daily (BID) + latanoprost; or latanoprost monotherapy. The primary endpoint was change in mean diurnal IOP from baseline at day 28.

Results: A total of 194 subjects were randomized, and 193 (99.5%) completed the study. Razuprotafib BID + latanoprost resulted in a significantly larger reduction in diurnal IOP than latanoprost alone (7.95 ± 0.26 mmHg vs. 7.04 ± 0.26 mm Hg, P < 0.05). A smaller improvement was observed after 14 days of treatment (7.62 ± 0.26 mm Hg vs. 7.03 ± 0.26 mm Hg, P = 0.11). Razuprotafib QD dosing did not demonstrate additional IOP lowering compared to latanoprost alone. Conjunctival hyperemia on Day 28 increased by 1.1 units on the four-point Efron scale two hours post dose from a baseline value of 0.6 units, and decreased thereafter.

Conclusions: Topical ocular razuprotafib as an adjunct to latanoprost therapy was well tolerated and significantly reduced IOP in patients with OAG/OHT.

Translational relevance: These data support the IOP lowering efficacy of targeting Tie2 activation in Schlemm's canal in the relevant patient population.

Figure 1.

Disposition of patients within the REAL study (Razuprotafib Tie 2 Activation as adjunct to Latanoprost) in patients with OAG or OHT.

Figure 2.

Change in mean diurnal IOP by treatment group after 14 and 28 days of treatment. (A) Overall effect. (B) Subgroups with IOP of <26 mm Hg and ≥26 mm Hg after washout. The numbers below the SEM bars indicate the mean reduction in IOP in each group or subgroup. Numbers at the top of the bars indicate number of patients in each group or subgroup. * P = 0.01 versus Latanoprost.

Figure 3.

Mean IOP by time point and treatment group. The numbers 8, 10, 12, and 16 on the x-axis refer to the individual post-dose time points, 8:00 (pre-dose), 10:00, 12:00, and 16:00 hours, respectively, comprising the diurnal IOP at baseline, day 14, and day 28. Only a single IOP measurement was taken at screening, qualification 1, and day 7 visits.

Figure 4.

Mean worst eye conjunctival hyperemia grade at Baseline and Days 14 and 28 using the five-point Efron bulbar conjunctiva hyperemia scale (0 = Normal, 1 = Trace, 2 = Mild, 3 = Moderate, 4 = Severe).