Figure 22.1 Study design of the phase 2 study describes the three patient groups randomized for treatment and the monthly dosing scheme.
Table 22.1 BASELINE DEMOGRAPHICS
The investigators studied and documented safety issues to include ocular and systemic adverse events (AE) and serious adverse events (SAE). Ocular AE were reported as conjunctival hemorrhage, punctate keratitis, eye pain, conjunctiva hyperemia, subretinal fibrosis, and increased intraocular pressure. These were reported in less than 5% of patients and were evenly distributed among the three groups. SAE involving the eye, including corneal erosion, uveitis, and reduced VA, were seen in less than 1% of patients. In regards to systemic safety issues, cardiac disorders, nonfatal myocardial infarctions (MI), nonfatal strokes, and vascular deaths were equally distributed among the three groups of patients (Tables 22.2, to 22.4).
Table 22.2 OCULAR ADVERSE EVENTS REPORTED IN ≥5% OF PATIENTS
Table 22.3 OCULAR SERIOUS ADVERSE EVENTS
Table 22.4 SYSTEMIC SERIOUS ADVERSE EVENTS
aData are listed for organ classes with three or more events.
bAntiplatelet Trialists’ Collaboration.
The efficacy of combination therapy of intravitreal Fovista and Lucentis and its superiority over Lucentis monotherapy were demonstrated in this study, when the investigators evaluated change in VA from baseline, improvement in vision over time, significant visual gain, optical coherence tomography (OCT) studies, and fluorescein angiography.
At the 24-week end point, Fovista combined with Lucentis met its prespecified primary end point with both Fovista/Lucentis groups achieving a mean change in vision from baseline greater than that of monotherapy (Fig. 22.2). In evaluating dose–response curves of the three groups, those patients receiving Fovista and Lucentis had demonstrable mean change in vision for all time points during the study (Fig. 22.3). Most compelling was the significant visual gain, defined as gaining more than three, four, or five lines of vision, as patients on combination therapy showed a 190% relative benefit in those patients gaining greater than five lines. OCT studies of the three groups showed similar findings when evaluating subretinal fluid, intraretinal cystic fluid, and sub-RPE fluid (Fig. 22.4). An interesting finding was the diminished percentage of patients who developed subretinal hyperreflective material (SHRM), in those eyes receiving combination therapy (Fig. 22.5). On angiography, there was a greater reduction in the CNV size seen in patients receiving combination therapy (Fig. 22.6).
Figure 22.2 Combination therapy with Fovista and Lucentis was superior to Lucentis alone when evaluating letters gained from baseline.
Figure 22.3 The dose–response curves of the three treatment groups reveals increased VA improvement in patients treated with Fovista in combination with Lucentis.
Figure 22.4 OCT of all three treatment groups showed comparable results in the analysis of subretinal fluid and intraretinal cysts.
Figure 22.5 An interesting finding was the diminished percentage of patients who developed sub-retinal hyper-reflective material (SHRM), in those eyes receiving combination therapy.
Figure 22.6 On angiography, there was a greater reduction in the CNV size seen in patients receiving combination therapy.
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