麻豆传媒

VANCOUVER -- Patients with neovascular age-related macular degeneration (AMD) received uninterrupted anti-VEGF therapy for more than a year with an infusion device implanted in the eye, a researcher said here.

In a phase II study, the median time to first refill was 15 months among patients randomized to the highest concentration of ranibizumab (Lucentis). Patients assigned to lower concentrations of the anti-VEGF agent had median refill times of 13 and 8.7 months. A standard-therapy control group received monthly injections of ranibizumab.

Treatment with the port delivery system (PDS) with the highest concentration of ranibizumab led to vision outcomes similar to that of monthly injections, Carl C. Awh, MD, of Tennessee Retina in Nashville, Tennessee, reported here at the meeting.

"The phase II goal was achieved, as dose-response was observed across the endpoints," Awh said in conclusion. "In the group that received the PDS with the 100 mg/mL concentration of ranibizumab, the median time to first required refill exceeded 15 months, and 80% of patients went 6 months or longer until the first required refill. Best corrected visual acuity (BCVA) and anatomic outcomes were comparable to those of monthly intravitreal ranibizumab.

"The PDS implant insertion surgery and refill procedure were well tolerated. The systemic safety was comparable to monthly intravitreal injections."

A phase III trial of the PDS with fixed-interval dosing will begin by the end of 2018, he added.

Slightly larger than a grain of rice, the PDS addresses one of the key drawbacks to anti-VEGF therapy for AMD: need for regular intravitreal injections, which can occur as often as monthly. The PDS has a proprietary delivery mechanism that provides for continual delivery of a preset amount of drug comparable to monthly injections.

The PDS is inserted into the pars plana during a procedure that is comparable to cataract surgery, said study investigator David A. Eichenbaum, MD, of Retina Vitreous Associates of Florida in St. Petersburg. The device is refilled by means of a minimally invasive procedure performed with local anesthesia in the office or clinic.

Awh reported findings from the phase II trial, which included 220 patients with neovascular AMD randomized 3:3:3:2 to the PDS prefilled with 100, 40, and 10 mg/mL of ranibizumab or to standard monthly intravitreal injections of the drug. The primary endpoint was time to first required refill of the PDS.

The study population had a mean age of about 72 and mean baseline BCVA of about 70 ETDRS letters. The time since diagnosis of neovascular AMD was 3.4 months, and the patients had received an average of three injections of anti-VEGF therapy prior to enrollment in the trial.

Results showed median refill times that corresponded to the baseline drug concentration in the PDS. Awh reported that 80% of patients in the 100 mg/mL group did not require refill for 6 months or longer. In the groups assigned to lower concentrations of ranibizumab, 71.3% and 63.5% had refill intervals ≥6 months.

Baseline BCVA was comparable among the four treatment groups. At 9 months, the mean BCVA improved by 4.3 ETDRS letters in the PDS 100 mg/mL group as compared with 3.3 letters in the patients assigned to monthly ranibizumab injections. Mean BCVA declined by 0.5 and by 3.2 letters in the groups assigned to the PDS with lower concentrations of ranibizumab.

Central foveal thickness increased in patients assigned to lower PDS ranibizumab concentrations and decreased by 6.9 µM with monthly ranibizumab injections and by 3.4 µM with the PDS 100 mg/mL group.

Adverse events occurred more often in the PDS groups, particularly in the postsurgical period. Vitreous hemorrhage occurred in about 50% of patients prior to optimization of the PDS implant procedures but declined to 4.3% thereafter, Awh reported. No more than one patient in each group developed infection.

"If the port system is validated in phase III, it could significantly reduce the treatment burden on patients with wet macular degeneration, with regard to the visits and injections that we do," Eichenbaum told 麻豆传媒. "It is burdensome for this elderly population to come in and get shots somewhere between every 4 and every 12 weeks. Most people need shots around every 8 to 10 weeks, but it really is a heterogeneous disease."

He said patients tolerate the injections well, but "there is some discomfort and a cost and a hassle associated with the frequent injections that we're trying to get away from as a field."

Comment