Better Treatments, Better Treatment Delivery for Wet AMD

By Peter K. Kaiser, MD

Although more treatment options for wet age-related macular degeneration (AMD) are available today than ever before, most of them require patients to receive regularly scheduled, indefinite intravitreal injections. Fortunately, many less burdensome modalities are now in development. At Cole Eye Institute, we are participating in several clinical trials searching for ways to reduce the treatment burden patients face with traditional anti-VEGF therapy. We also hope some of these new options will yield improved patient outcomes.

Platelet-derived growth factors

The use of platelet-derived growth factors (PDGFs) is the most advanced of the alternative pathways we are investigating. Two drugs that utilize an anti-PDGF pathway are in phase 3 studies.

One of them, pegpleranib (Fovista®, Ophthotech), is used in combination with anti-VEGF agents, so it requires two injections. Fovista’s phase 2 large study saw improvements in visual acuity almost from the beginning of treatment. Our phase 3 study is fully enrolled, and we hope we will see significant improvements in patient outcomes.

The second PDGF-inhibitor drug in phase 3 studies is squalamine (OHR-102, Ohr Pharmaceutical), also used in combination with an anti-VEGF injection (ranibizumab). Similar to the phase 2 study of Fovista, Ohr’s phase 2 study showed that the combination therapy yielded better results than did anti-VEGF monotherapy. OHR-102 offers a distinct benefit to patients because it is an eye drop instead of an injection.

Other companies are looking at the PDGF pathway, including Regeneron Pharmaceuticals Inc., which is conducting a large phase 2 study of a treatment that combines aflibercept (Eylea®, Regeneron) and rinucumab, an antibody to the PDGF receptor.

Other options under study

Other options under investigation include:

• Anti-integrin pathways: Integrins are cell surface molecules that help in the angiogenic cascade. ALG-1001 (Luminate®, Allegro Ophthalmics), an integrin antagonist, is being studied as monotherapy and in combination with anti-VEGF therapy.
• Third-generation anti-VEGF agents: Improvements in the longevity of anti- VEGF agents could provide efficacy with less frequent injections. RTH258 (Alcon Laboratories) and abicipar pegol (DARPin®; Allergan) are both in phase 3 studies.
• Improved delivery options: Another idea in development is the delivery of anti-VEGF therapy via a sustained-release implant. Genentech has developed a ranibizumab port delivery system (RPDS) implant that can be refilled in the clinician’s office. The goal for an optimal replacement schedule is about six months.

Another possible improvement in delivery options comes from Alcon, which has developed a micropump that functions like an electronic reverse Ahmed valve. Instead of taking fluid out of the eye, the reservoir slowly injects a drug into it. The device also can be refilled in the office. Alcon is testing the pump with brolucizumab.

We hope these advances will help reduce the endless need for injections and potentially allow us to reverse at least some of the impact of AMD on patients’ vision.

Dr. Kaiser is the Chaney Family Endowed Chair of Ophthalmic Research and staff at Cole Eye Institute.