番茄社区

The ranibizumab port delivery system (PDS; Susvimo) with 6-month refill maintained noninferiority to monthly intravitreal injections for neovascular age-related macular degeneration (nAMD) out to 2 years, according to updated results from a randomized trial.

Three assessments of best corrected visual acuity (BCVA) during years 1 to 2 showed differences ranging from -0.2 to +0.4 ETDRS (Early Treatment Diabetic Retinopathy Study) letters for the PDS versus monthly injections. The values were compared with a prespecified noninferiority threshold of -3.9 letters. During four refill periods through week 96, 95%-98% of patients randomized to the PDS did not require supplemental ranibizumab (Lucentis).

Adverse events (AEs) of special interest occurred more often with the PDS than with standard therapy, reported Carl Regillo, MD, of the Wills Eye Hospital at Thomas Jefferson University in Philadelphia, and co-authors in .

"These results indicate that the continuous delivery of anti-VEGF [vascular endothelial growth factor] therapy via PDS provides consistent benefits in patients with nAMD for 2 years, and additional long-term data up to 5 years are being collected in the ," the authors wrote in their conclusion.

Ongoing trials will provide insights related to the safety and efficacy of the PDS in diabetic macular edema and diabetic retinopathy without macular edema, they added.

The positive results came to light as the PDS remains off market while Genentech continues to evaluate causes and solutions for an apparent defect in a seal that would allow medication to leak from the implant. Genentech the device in October 2022, an action that affected only new device implants. Patients with existing implants that had not had problems could continue to get refills.

At the time of the recall, company officials said they hoped the problem could be resolved within a year and the device could be back on the market. In response to a 番茄社区 inquiry about the status of the recall, Genentech wrote in an email that the company is "working to bring Susvimo back as soon as possible. Since the voluntary recall of Susvimo in October 2022, significant progress has been made to identify and start implementing solutions. Ongoing performance testing has enabled us to identify areas for improvements to the implant manufacturing process and the system overall. We are exploring these potential improvements and will provide details when available."

The PDS received FDA approval in 2021, offering the benefit of replacing monthly intravitreal injections with a semi-annual refill of the device. At the time, Regillo called the PDS "a major advancement in the treatment of retinal disease and an important new option for patients with wet AMD."

Primary support for the approval came from the phase III Archway study, which demonstrated the noninferiority of the PDS to standard monthly injections for control of nAMD. After a median follow-up of 40 weeks, patients randomized to the PDS had a mean increase of 0.2 letters and a 2.8-µm change in retinal thickening versus standard treatment, both of which met prespecified criteria for noninferiority.

Regillo and co-authors reported findings from a 24-month follow-up of the Archway study. Eligible patients ages 50 and older had documented nAMD and response to anti-VEGF therapy. Investigators at 78 U.S. sites randomized 415 patients 3:2 to the PDS or monthly intravitreal ranibizumab. The primary endpoint was change in BCVA from baseline averaged over weeks 36 and 40, with a noninferiority threshold of -3.9 ETDRS letters.

Follow-up continued to 2 years with focus on the primary endpoint and safety, as well as secondary endpoints. The end-of-study results showed that the 1-year results were maintained during an additional year of follow-up. Assessments at 1 year, 18 months, and 2 years showed differences between the PDS and standard therapy of -0.2, +0.4, and -0.6 letters, respectively. Changes from baseline in retinal thickness also were comparable between treatment groups and within prespecified limits for noninferiority.

The proportion of patients in the PDS arm who required no supplemental or rescue anti-VEGF therapy was a secondary outcome. At the first 6-month refill period, 98% of patients in the PDS arm had not received supplemental treatment, declining slightly to 95% at the three subsequent prespecified refill periods.

AEs of special interest occurred in 23.8% of patients in the PDS group versus 10.2% of those in the standard-therapy arm. The most common AE of special interest in both arms was cataract (8.9% with the PDS vs 6.0% with monthly injections). Other AEs of interest in the PDS arm included conjunctival erosions (4.0%), conjunctival retractions (2.4%), endophthalmitis (1.6%), and implant dislocation (1.6%).

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