Age-related macular degeneration (AMD) is one of the primary causes of blindness among adults, particularly in its wet form known as Neovascular AMD caused by Choroidal Vascular Disease.

Anti-VEGF treatments typically consist of monthly anti-VEGF injections; however, a new option uses an implant which gradually releases ranibizumab over time. Long-term studies indicate it could significantly decrease the number of treatments patients require each year.

Genentech’s Susvimo® (ranibizumab) Refillable Ocular Implant)

As more Americans suffer from age-related macular degeneration, so too has their need for treatments increased. Many of these therapies target vascular endothelial growth factor (VEGF). Drugs targeting this substance help prevent blood vessels that lead to fluid build-up in retina and vision loss from forming; monthly anti-VEGF injections have traditionally been the go-to approach; however a promising new therapy could potentially cut this number from twelve down to two annually.

FDA recently granted approval of Susvimo, a refillable ocular implant which delivers ranibizumab continuously and with less risk of side effects than Lucentis injections. Once in place during an outpatient procedure, refills must be received every six months. Unlike its injectable equivalent, Susvimo offers sustained drug dosage.

Genentech’s Vabysmo implant combines an antibody with a special delivery system for use in eye injection. Once filled, an eyedropper injects it through its tiny needle into its target location for administration into the eye, refilling with more medication as necessary.

Researchers studied two groups of patients who received either monthly aflibercept injections or the Susvimo implant. After conducting their study, researchers noticed that those receiving implants showed improved vision over time as measured by an Amsler grid test versus those receiving injections; researchers concluded that both methods delivered comparable results.

This study was jointly conducted by the University of Pennsylvania and National Institutes of Health. Patients were randomly assigned either an implant or injections; results demonstrated that both offered similar levels of vision improvement.

However, the implant has been associated with an increased risk of endophthalmitis; in multiple clinical trials this side effect was observed in approximately 2% of those receiving implants; the vast majority of cases related to conjunctival retraction or erosion could likely have been avoided through proper care and treatment.

The Potential of a One-Time Gene Therapy

Eyes are remarkable organs in that they allow for targeted medication delivery, making the eye an ideal target for gene therapy treatments to target retinal diseases locally and potentially without frequent injections or treatments altogether. Unfortunately, however, such transformative therapies often carry hefty price tags; Retina specialists Carl Regillo and Diana Do have been alerted to newer therapies being explored for wet AMD that offer improved outcomes with reduced treatments at a more reasonable cost.

Wet age-related macular degeneration (AMD) is one of the primary causes of irreversible vision loss among adults, caused by abnormal blood vessels growing on the retina at the back of the eye. This form is more advanced and difficult to treat than dry forms. Anti-vascular endothelial growth factor (VEGF) therapy is now considered standard care, as it helps decrease vascular permeability and angiogenesis. Clinical trials have demonstrated the efficacy of certain agents to decrease choroidal neovascularization in those suffering from neovascular AMD and stabilize acuity for those diagnosed with DR; however, real world data have demonstrated poor adherence and suboptimal results compared with clinical trial results. New therapies aim to address this by expanding therapeutic targets, using innovative drug delivery systems, or offering longer-acting expression to decrease intraocular injection frequency.

Susvimo’s Safety

Susvimo, commonly referred to as the Port Delivery System (PDS), is a refillable ocular implant that continuously releases ranibizumab. After being implanted through one surgical procedure and periodically replenished by clinicians every six months. Clinical trials showed it gave wet macular degeneration patients vision gains equivalent to those seen when injecting ranibizumab monthly, according to Genentech reports.

In both the YOSEMITE and RHINE studies, at least 60 of faricimab-treated DME patients were able to extend their treatment intervals up to every four months at two years, while 95% of wet AMD patients in Archway could go six months between treatments–their fourth completed refill-exchange interval–and still maintain vision outcomes which were non-inferior to those receiving monthly ranibizumab injections.

These results highlight the potential of Vabysmo and Susvimo to transform standards of care for neovascular age-related macular degeneration and diabetic macular edema while simultaneously decreasing patient treatment needs annually. They also support biobetters expected to provide superior efficacy and safety compared to reference biologics such as bevacizumab (Avastin), Beovu/Zirabev combination therapies (Beovu/Zirabev), or Aflibercept (Eylea).

Current methods of treating wet macular degeneration involve injecting intravitreal anti-VEGF injections every month or bimonthly; if Susvimo proves as effective and safe as existing injectable drugs, however, treatment could potentially be reduced from 12 injections annually to two injections annually.

However, implants don’t come without risks. According to a review of ophthalmology biosimilars and biobetters published by Drug Discovery Today in May 2017, implants are linked with three times more infections than traditional intravitreal injections. Due to its unique delivery method, implants often sit directly on the eye, providing more easy entry for bacteria into the eye. However, most infections tend to be mild and usually resolve themselves quickly. Patients and providers must carefully assess the risk of infection before implanting an implant into patients or themselves. Future studies should help better understand this innovative therapy’s risks as well as ways to mitigate them.

Susvimo’s Efficacy

Wet macular degeneration (neovascular AMD) is an eye condition which affects the macula, or central vision portion of retina that provides sharp central vision required for tasks like driving and reading. Without treatment, losing this vital area could result in blindness.

For years, wet macular degeneration was treated by providing regular intravitreal anti-VEGF injections to maintain visual clarity. While effective and beneficial for many patients, their monthly administration could become burdensome; with newer drugs offering extended duration effects such as Eylea and Vabysmo helping ease some of this treatment burden.

Genentech made another advancement last year when they gained FDA approval for Susvimo (formerly Port Delivery System (PDS). Susvimo is a permanent eye implant that surgically installs a refillable port into each eye and gradually releases ranibizumab at regular intervals over time.

At two years, data from the YOSEMITE and RHINE studies in DME as well as Archway Study in wet AMD demonstrated that Susvimo allows for shorter treatment sessions with extended intervals between refills while still producing visual outcomes comparable to monthly ranibizumab injections. 95% of individuals in Archway Study who received Susvimo at fourth refill-exchange interval achieved six month treatment gaps or longer between treatments!

An implant may create a bump on the white layer of the eye (conjunctiva) where it’s located, requiring medical or surgical treatment due to build-up of fluid around it. Another side effect could include cataract formation.

As apparent as its advantages are, further research must be undertaken. Susvimo must prove its long-term safety and efficacy to determine if it can offer an alternative or complementary method to standard of care; the ophthalmology community awaits results of further investigations on this promising new technology.