Genentech's Susvimo, formerly PDS with ranibizumab, receives US FDA approval

Genentech has received approval from the US FDA for Susvimo, previously called the Port Delivery System (PDS) with ranibizumab (Lucentis, Genentech), the first wet, or neovascular, AMD treatment in 15 years to provide an alternative to standard-of-care eye injections needed as often as once a month.

The drug is billed as a first-of-its-kind therapeutic approach for wet age-related macular degeneration (AMD) and may help people with the disease maintain their vision with as few as 2 treatments annually.

According to Genentech, the treatment is for intravitreal use via ocular implant to treat people with wet AMD who have previously responded to at least 2 anti-vascular endothelial growth factor (VEGF) injections. The company stated that Susvimo is the first and only FDA-approved treatment for wet AMD that offers as few as 2 treatments per year.

“Susvimo represents a major advancement in the treatment of retinal disease, and is an important new option for patients with wet AMD,” Dr Carl Regillo, chief of Retina Service at Wills Eye Hospital in Philadelphia and an Archway study investigator, said in a statement. “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.”

Genentech noted that Susvimo delivers ranibizumab continuously, offering patients living with wet AMD an alternative to anti-VEGF eye injections needed as often as once a month. The implant is surgically inserted into the eye during a one-time, outpatient procedure and refilled every 6 months. If necessary, supplemental ranibizumab treatment can be given to the affected eye while the Susvimo implant is in place.

Dr Levi Garraway, Genentech’s chief medical officer and head of Global Product Development, said in a statement that the company believes that Susvimo can help people with wet AMD preserve their vision while potentially alleviating the treatment burden associated with current standards of care.

“Susvimo’s approval builds on Genentech's long-standing commitment to people living with vision-threatening conditions,” Garraway said in the statement.

Archway trial results

According to the company, the FDA approval comes after positive results from the randomly assigned multicentre Phase III Archway study primary analysis, which showed wet AMD patients treated with Susvimo achieved and maintained visual gains equivalent to monthly ranibizumab injections – +0.2 and +0.5 eye chart letters from baseline, respectively – at weeks 36 and 40 of treatment.

Susvimo, which contains 100 mg/ml of ranibizumab, was non-inferior and equivalent to monthly 0.5-mg ranibizumab injections for changes in the best-corrected visual acuity compared with baseline at the average of weeks 36 and 40 and remained non-inferior through 2 refill-exchange intervals at the average of weeks 44 and 48.

The visual and anatomic results with the PDS were comparable to those with monthly ranibizumab through week 72 regardless of the presence or absence of subretinal or intraretinal fluid.

The presence of intraretinal fluid in the central 1 mm of the retina was associated with worse vision outcomes, which was consistent with the findings of other trials.

Continuous delivery of ranibizumab via the PDS every 24 weeks maintained the vision outcomes, regardless of the overall presence or absence of retinal fluid.

Moreover, only 1.6% of Susvimo patients received supplemental ranibizumab treatment before their first refill, and more than 98% could go six months before their first refill.

In the Archway study, Susvimo was generally well-tolerated, with a favorable benefit-risk profile. However, the Susvimo implant has been associated with a 3-fold higher rate of endophthalmitis than monthly intravitreal injections of ranibizumab.

According to the company, many of these events were associated with conjunctival retractions or erosions. Appropriate conjunctival management and early detection with surgical repair of conjunctival retractions or erosions may reduce the risk of endophthalmitis.

In clinical trials, 2% of patients receiving a ranibizumab implant experienced at least 1 episode of endophthalmitis. The most common adverse events were conjunctival haemorrhage, conjunctival hyperemia, iritis and eye pain. The safety profile of Susvimo in the clinical trial setting is well understood and will continue to be monitored closely.

Genentech has a robust phase III clinical development program for Susvimo, including the Portal, Pagoda, Pavilion, and Velodrome studies. Portal is an extension study evaluating the long-term safety and efficacy of Susvimo in wet AMD. Pagoda is evaluating Susvimo for the treatment of people with diabetic macular oedema (DMO), while Pavilion is a study of Susvimo in diabetic retinopathy without DMO. Velodrome is evaluating Susvimo refilled every 9 months in wet AMD. Susvimo is also currently under review for the treatment of wet AMD by the European Medicines Agency.

According to Genentech, Susvimo will be available in the United States in the coming months, and the company is committed to helping patients access the medicines they are prescribed and will be offering comprehensive services for people prescribed Susvimo to help minimise barriers to access and reimbursement.

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