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Refillable port delivery system

19 evidence topics · 7 sources

Ranibizumab port delivery system: boxed warning for endophthalmitis

“The SUSVIMO implant has been associated with an up to 3-fold higher rate of endophthalmitis than monthly intravitreal injections of ranibizumab. Many of these events were associated with conjunctival retractions or erosions.” (opens the source at this quote in a new tab)

Ranibizumab port delivery system: indication and dosing

“Neovascular (wet) Age-related Macular Degeneration (AMD) who have previously responded to at least two intravitreal injections of a VEGF inhibitor (1.1).” (opens the source at this quote in a new tab)
“The recommended dose of SUSVIMO (ranibizumab injection) is 2 mg (0.02 mL of 100 mg/mL solution) continuously delivered via the SUSVIMO implant with refills every 24 weeks (approximately 6 months).” (opens the source at this quote in a new tab)
“Supplemental treatment with 0.5 mg intravitreal ranibizumab injection may be administered in the affected eye if clinically necessary.” (opens the source at this quote in a new tab)

Ranibizumab port delivery system: Archway phase 3 trial

“Archway enrolled 418 patients; 251 were randomized to and 248 received treatment with the PDS Q24W, and 167 were randomized to and received treatment with monthly ranibizumab.” (opens the source at this quote in a new tab)
“Adjusted mean change in BCVA score from baseline averaged over weeks 36 and 40 was +0.2 letters (standard error [SE], 0.5 letters) in the PDS Q24W arm and +0.5 letters (SE, 0.6 letters) in the monthly ranibizumab arm (difference, -0.3 letters; 95% confidence interval, -1.7 to 1.1 letters).” (opens the source at this quote in a new tab)
“Prespecified ocular adverse events of special interest were reported in 47 patients (19.0%) in the PDS Q24W arm and 10 patients (6.0%) in the monthly ranibizumab arm, which included, in the former arm, 4 (1.6%) endophthalmitis cases, 2 (0.8%) retinal detachments, 13 (5.2%) vitreous hemorrhages, 6 (2.4%) conjunctival erosions, and 5 (2.0%) conjunctival retractions.” (opens the source at this quote in a new tab)

Ranibizumab port delivery system: label supplemental treatment and endophthalmitis rates

“In the first 24 weeks, 1.6% of patients assessed for supplemental treatment received 1 or more supplemental treatment(s) and in the following 24 weeks, 5.4% of patients assessed for supplemental treatment received 1 or more supplemental treatment(s).” (opens the source at this quote in a new tab)
“In the active comparator period of controlled clinical trials in AMD, the ranibizumab implant has been associated with a 3-fold higher rate of endophthalmitis than monthly intravitreal injections of ranibizumab (1.7% in the SUSVIMO arm vs 0.5% in the intravitreal arm). When including extension phases of clinical trials, 2% (11/555) of patients receiving the ranibizumab implant experienced an episode of endophthalmitis.” (opens the source at this quote in a new tab)

Ranibizumab port delivery system: septum dislodgement

“In clinical trials, a type of implant damage where the septum has dislodged into the implant body has been reported.” (opens the source at this quote in a new tab)
“The benefits and risks of retaining, removing, or removing and replacing an implant with a dislodged septum are not well characterized.” (opens the source at this quote in a new tab)

Ranibizumab port delivery system: endophthalmitis case series across clinical trials

“Twelve endophthalmitis events were reported in 11 patients (11/555 [2.0%]) through March 12, 2021.” (opens the source at this quote in a new tab)
“Seven cases (7/11 [63.6%]) had preceding/concurrent conjunctival complications. At last follow-up, 7 patients recovered vision to study baseline levels or ≥20/40; 4 patients experienced vision loss of ≥15 ETDRS letters.” (opens the source at this quote in a new tab)

Ranibizumab port delivery system: Portal extension trial

“In the All-PDS safety population (mean follow-up, 111 weeks), 137 (24.7%) patients had ≥1 ocular AESI; most common were cataract (11.4%), vitreous hemorrhage (6.1%), and conjunctival thickening (bleb)/filtering bleb leak (6.3%). Endophthalmitis occurred in 11 of 555 (2.0%) patients.” (opens the source at this quote in a new tab)
“Approximately 95% of patients did not need supplemental treatment before each refill-exchange for >2 years since Portal enrollment.” (opens the source at this quote in a new tab)

Ranibizumab port delivery system: 5-year Portal results

“In the Susvimo cohort, best-corrected visual acuity (BCVA) was 74.4 letters at baseline and 67.6 letters at 5 years. In the IVT-Susvimo cohort, BCVA was 76.3 letters at baseline and 68.6 at 5 years.” (opens the source at this quote in a new tab)

Ranibizumab port delivery system: voluntary recall and reintroduction

“Susvimo was approved by the FDA in 2021. The following year, Genentech voluntarily recalled the ocular implant, insertion tool and initial fill kit in the U.S. following test results that showed some implants did not perform to Genentech’s standards.” (opens the source at this quote in a new tab)
“The U.S. Food and Drug Administration (FDA) has approved a post-approval supplement to the Biologics License Application for Susvimo, reflecting component-level updates made to the ocular implant and refill needle.” (opens the source at this quote in a new tab)

AAO Preferred Practice Pattern: port delivery system risks and cost-effectiveness

“Importantly, after using the implant, there was a 2% risk of endophthalmitis in clinical trials (a rate three times higher than monthly intravitreal injections of ranibizumab).” (opens the source at this quote in a new tab)
“They found that although the implant seemed to compare favorably at $21,825 with two ranibizumab 100-mg/ml fills at 1 year compared with $18,405 for 11.8 injections of ranibizumab 0.5 mg over that same time period, this benefit did not seem to extend to 5- and 12-year time points.” (opens the source at this quote in a new tab)

Timing of endophthalmitis after port delivery system implantation

“There were 2 cases (2/555 [0.4%]) of postoperative endophthalmitis consistent with acute postoperative endophthalmitis.” (opens the source at this quote in a new tab)
“The range of onset for all other cases was 57 to 853 days after the PDS implant insertion procedure (Table 3), including 6 cases occurring in the first year after the PDS implant insertion procedure and 1 case occurring >2 years after the PDS implant insertion procedure (Fig 2).” (opens the source at this quote in a new tab)
“The retraction cases presented relatively earlier in the first year after surgery, with onset ranging between 2 to 6 months after implantation surgery, whereas the erosion cases presented later, with onset ranging from 20 to 28 months after implantation surgery.” (opens the source at this quote in a new tab)

Severity, organisms, and management of port delivery system endophthalmitis cases

“all patients experienced moderate (4/11 [36.4%]) or severe (7/11 [63.6%]) endophthalmitis when events were analyzed by greatest intensity.” (opens the source at this quote in a new tab)
“Three cases of endophthalmitis were culture positive (1 case each of Streptococcus pneumoniae, Enterococcus faecalis, Staphylococcus aureus; the case positive for E. faecalis reported history of exposure to a septic tank 1 week prior).” (opens the source at this quote in a new tab)
“Vitrectomy was performed for endophthalmitis in 5 cases; vitrectomy and a scleral wound revision was performed after endophthalmitis had resolved for 1 additional case to treat a subsequent event of wound leak/hypotony.” (opens the source at this quote in a new tab)
“Six patients had the PDS implant removed after their endophthalmitis episode per surgeon's preference, and 1 patient with endophthalmitis associated with E. faecalis discontinued refills but retained the implant at the surgeon's discretion.” (opens the source at this quote in a new tab)

Serious ocular adverse events of special interest in the pooled port delivery system population

“Other important ocular AESIs included conjunctival erosion (reported in 4.0% [22/555] of patients), conjunctival retraction (1.8% [10/555]), endophthalmitis (2.0% [11/555]), hyphema (1.6% [9/555]), implant dislocation (1.1% [6/555]), rhegmatogenous retinal detachment (0.7% [4/555]), and septum dislodgement (0.5% [3/555]) (Table 6).” (opens the source at this quote in a new tab)
“Among ocular AESIs reported as serious, the most common were endophthalmitis (1.8% [10/555]), conjunctival erosion (1.3% [7/555]), and conjunctival retraction (0.9% [5/555]; Table 6).” (opens the source at this quote in a new tab)
“Overall, 73.0% (27/37) of vitreous hemorrhage events were mild; most (91.9% [34/37]) resolved with observation.” (opens the source at this quote in a new tab)
“The majority of conjunctival bleb events involved fluid and most resolved after approximately 11 (mean, 11.21) weeks, without the need for additional procedures.” (opens the source at this quote in a new tab)

Septum dislodgement and the 2022 voluntary recall

“Since the March 2021 data cut used for the current analysis, there were an additional 30 septum dislodgements to August 2022 across the PDS clinical trials.” (opens the source at this quote in a new tab)
“Due to additional testing conducted during an investigation into septum dislodgement cases in phase III clinical trials, Roche/Genentech initiated a voluntary recall of the PDS Ocular Implant and Insertion Tool Assembly in October 2022 and paused all new implantations.” (opens the source at this quote in a new tab)

Number and timing of supplemental injections between refill-exchanges in Portal

“Across all treatment arms, 39 supplemental treatments were administered in 21 patients (data not shown).” (opens the source at this quote in a new tab)
“Of these, 32 supplemental treatments occurred 8 weeks before a refill-exchange, and 7 occurred 4 weeks before a refill-exchange.” (opens the source at this quote in a new tab)
“Of the 21 patients, 9 received 1 treatment, 9 received 2 treatments, 2 received 3 treatments, and 1 received 5 treatments.” (opens the source at this quote in a new tab)

Ocular adverse events associated with persistent vision loss and their timing

“Six of 7 episodes of conjunctival erosion that occurred across the analysis period were associated with significant persistent vision loss, of which 2 were repeat events.” (opens the source at this quote in a new tab)
“One episode of endophthalmitis occurred 2.3 years after implantation in Ladder and was attributed to the refill-exchange procedure.” (opens the source at this quote in a new tab)
“As shown by the distribution of ocular AESIs over time, all events that occurred >2 years after PDS implantation were in patients who received the PDS implant earlier in the PDS clinical trial program, and surgical procedures have since been further optimized.” (opens the source at this quote in a new tab)

Supplemental treatment before the first refill-exchange in Archway

“Of 246 PDS-treated patients assessed for supplemental ranibizumab treatment, 242 (98.4%) did not receive supplemental ranibizumab treatment before the first refill-exchange procedure, including 4 patients who discontinued treatment before the first refill-exchange procedure.” (opens the source at this quote in a new tab)
“In total, 4 PDS-treated patients (1.6%) who were assessed for supplemental treatment received supplemental treatment before the first refill-exchange procedure.” (opens the source at this quote in a new tab)

Timing and surgical management of ocular adverse events in Archway

“Most ocular adverse events in the PDS Q24W arm occurred within 1 month of implantation.” (opens the source at this quote in a new tab)
“endophthalmitis occurred in 4 patients (1.6%) in the PDS Q24W arm; all events were serious and occurred outside of the postoperative period at days 57, 59, 161, and 282. Three of the 4 events were associated with conjunctival retraction.” (opens the source at this quote in a new tab)
“Conjunctival erosion and conjunctival retraction events occurred in 6 patients (2.4%) and 5 patients (2.0%) in the PDS Q24W arm, respectively.” (opens the source at this quote in a new tab)
“In total, 9 of 11 patients required additional surgery, and events were addressed with conjunctival flap revisions; 3 repairs were performed using split-thickness corneal graft.” (opens the source at this quote in a new tab)

Vitreous hemorrhage, conjunctival bleb, and unscheduled visits in Archway

“Vitreous hemorrhage occurred in 13 patients (5.2%) in the PDS Q24W arm; 1 event was serious and 12 of 13 events occurred in the postoperative period.” (opens the source at this quote in a new tab)
“Eleven of 13 hemorrhages (84.6%) were grade 1 or 2 based on functional impact (Table S2, available at www.aaojournal.org), and all events resolved spontaneously without vitrectomy.” (opens the source at this quote in a new tab)
“Conjunctival bleb or conjunctival filtering bleb leak events were reported in 16 patients (6.5%) in the PDS Q24W arm. All events were nonserious.” (opens the source at this quote in a new tab)
“Of these 47 PDS patients, 16 underwent at least 1 unscheduled visit within 7 days of occurrence of an ocular adverse event of special interest, and 18 underwent at least 1 unscheduled visit within 14 days of occurrence.” (opens the source at this quote in a new tab)