The US FDA has approved a 100 mg/mL ocular implant (Port Delivery System) for the treatment of nAMD, sponsored by Roche (SIX: RO, ROG; OTCQX: RHHBY). The ocular implant, tested in the “Archway” trial (NCT03677934), used a randomised, multicentre, open-label phase III study with a refillable anti-VEGF treatment allowing fixed intervals for every six-months. According to Dr. Carl Regillo, M.D., Chief of Retina Service at Wills Eye Hospital in Philadelphia, and an Archway study investigator, stated that, “Susvimo (the ocular implant ‘Port Delivery System’ with ranibizumab) represents a major advancement in the treatment of retinal disease and is an important new option for patients with wet AMD. With Susvimo, my patients now have an option that can help them maintain their vision as well as anti-VEGF injections, but on a more manageable twice-yearly treatment schedule.”
In follow-up to the Archway study, the implant may be refilled every six months at fixed intervals, compared to monthly intravitreal injections of ranibizumab (0.5 mg) with 415 participants with nAMD. The trial was an RCT, multicenter, open-label Phase III study evaluating the efficacy and safety of the Port Delivery System with ranibizumab (PDS). The PDS is an implantable “reservoir-based, slow-release platform which sits in the sclera and delivers ranibizumab in a concentrated solution at different doses in the setting of nAMD”. In the two study arms, patients were treated with at least three anti-VEGF injections within the six months prior to their screening visit. The primary endpoint of the study was the change in BCVA score – including with correction such as glasses – from baseline at the average of week 36 and week 40. The study design used a non-inferior outcome, equivalent to monthly ranibizumab injections. The clinical results indicated that, on average, patients had received five prior ranibizumab injections before their first study initiation visit. In the PDS arm of the study, patients gained an average of 0.2 eye chart letters in visual acuity from baseline compared with 0.5 eye chart letters for the monthly ranibizumab arm. During the first treatment interval, before the first scheduled refill, 1.6% of PDS patients assessed (n=4/246) received supplemental treatment, and 98.4% of patients (n=242/246) did not receive supplemental treatment.
At the recent announcement, Roche stated that the implant has been associated with a three-fold higher rate of endophthalmitis than monthly intravitreal injections of ranibizumab. According to the data, many of the adverse events were associated with conjunctival retractions or erosions however, clinical management and early detection with surgical repair of conjunctival retractions or erosions may reduce the risk of endophthalmitis. The company stated that, in clinical trials, 2.0% of patients receiving a ranibizumab implant experienced at least one episode of endophthalmitis. The most common adverse events (AEs) were conjunctival haemorrhage, conjunctival hyperaemia, iritis and eye pain.