Retinal diseases, including wet AMD, are commonly treated with anti-VEGF therapies, and while these treatments can deliver significant improvements in vision, the need for frequent IVT injections is extremely burdensome. This burden of care leads to reduced patient compliance, resulting in sub-optimal visual outcomes, including retinal damage that may be irreversible.
Retinal Diseases and the Burden of Care
Wet age-related macular degeneration (wet-AMD), diabetic macular edema (DME) and retinal vein occlusion (RVO) are the most common retinal diseases. While they differ in cause, they all share the same mechanism of vision decline caused by excess VEGF. Currently approved anti-VEGF therapies work effectively, but retrospective analyses show that the burden involved in frequent visits for evaluation and treatment causes patients and physicians to extend treatment intervals, which in turn results in undertreatment and visual outcomes that fall short of results seen in clinical trials.
According to the National Eye Institute, more than one million people are diagnosed with AMD annually and the incidence is expected to grow as the population ages. Approximately 15 million people in the United States have macular degeneration, of which 10 to 15% have active blood vessel growth and leakage, or wet AMD. Without treatment, vision rapidly declines. The below graphic illustrates the primary effects of wet AMD.
Diabetic Retinopathy and Diabetic Macular Edema
Diabetic Retinopathy (DR) is a leading cause of vision loss globally, affecting up to 80% of those who have had diabetes for 20 years or more. Of the approximately 30 million people in the United States suffering from diabetes about 1.5 million have DME, with approximately 750,000 people being affected by a more serious form of the disease. DME affects central vision and can lead to a decline in vision ranging from slight visual blurring to blindness, substantially affecting independence and quality of life. Left untreated, DME is the most common cause of vision loss in patients with DR. The below graphic illustrates the primary effects of DME.
Retinal Vein Occlusion
RVO is a common chronic retinal vascular disease, resulting from a blockage of the veins that drain the retina. Blockage of blood vessels can lead to swelling of the retina, leading to the expression of VEGF which, in turn, leads to further vascular permeability and/or hemorrhage, and subsequent vision loss. Approximately 1.1 million people in the United States are affected by RVO. The below graphic illustrates the effects of RVO.
IVT injections have become the most commonly performed ophthalmic procedure in the United States, with an estimated six million injections performed in 2016 and an estimated annual growth rate of 10%. In clinical trials, it was demonstrated that monthly or bi-monthly IVT injections of anti-VEGF drugs lead to significant gains in visual acuity for patients with retinal diseases. While these treatments can deliver significant improvements in vision, the need for frequent IVT injections is extremely burdensome and leads to reduced patient compliance, resulting in sub-optimal visual outcomes, including retinal damage that may be irreversible.
Retinal practitioners surveyed by the American Society of Retinal Specialists responded that their three greatest unmet needs are:
- Long-acting sustained drug delivery
- Reduced treatment burden
- New treatment mechanisms of action.
According to patient interviews performed in the United States, France and Australia, the factors affecting adherence from the patient’s perspective included the psychosocial burden of repeated intravitreal injections, the time burden of both treatment and monitoring visits, which could take up to 12 hours per visit including travel time and often involved a caregiver, as well as the visual acuity benefits expected. Long-term observational studies in the United States, Europe and Japan have demonstrated that many patients with wet AMD are undertreated and are losing visual acuity simply because of the difficulty to receive anti-VEGF injections at an optimal frequency.
We believe that our proprietary ocular delivery technologies will allow us to develop therapeutics that will provide superior results to patients compared to existing anti-VEGF treatments, which present several critical limitations.
We believe that GB-102, our lead product candidate, can reduce the need for frequent IVT injections by expanding treatment duration to six months in retinal diseases, and we are exploring its use in several indications including wet AMD, DME, and RVO.
GB-102 is a microparticle depot formulation of the anti-VEGF sunitinib. Our proprietary depot formulation gradually releases the active ingredient, sustaining therapeutic drug levels in the ocular tissues for up to six months. Sunitinib is a small molecule receptor tyrosine kinase inhibitor which acts as a potent inhibitor of all VEGF pathways, which are known to cause angiogenesis and vascular leakage in the retina, leading to vision decline. The VEGF pathways play an influential role in the development and progression of wet AMD, and there is mechanistic and clinical evidence indicating that a more complete inhibition of these pathways, as offered by sunitinib, could lead to superior patient outcomes compared to current treatments that target only limited VEGF pathways, specifically VEGF-A. We believe that extending the duration of treatment while expanding the spectrum of neovascular inhibition of all VEGF pathways is differentiated from the current standard of care and may lead to better patient outcomes.
In January 2019, we announced positive top-line results for the ADAGIO study, a Phase 1/2a study of intravitreal GB-102 (sunitinib malate) in patients with wet AMD. This data was presented by David S. Boyer, M.D., of Retina Vitreous Associates, Beverly Hills, CA, during a presentation of “New Developments in Drug Therapy for Retinal Disorders” at the 2019 Hawaiian Eye & Retina annual meeting in Kona, Hawaii.
In September 2019, we initiated a Phase 2a study with GB-102 in patients with macular edema (ME) secondary to DME or RVO. The GB-102 Phase 2a open label, six-month study is intended to establish the safety of GB-102 and provide preliminary evidence of its durability in ME patients secondary to DME and RVO. All patients have been recruited into the study.
In September 2019, we also initiated a dose-ranging, double-blind Phase 2b clinical trial ALTISSIMO designed to evaluate the safety and efficacy of GB-102 in patients with wet AMD compared to bi-monthly IVT injections of aflibercept, marketed as Eylea.
GB-103 is a longer-acting formulation of sunitinib with the potential to deliver therapeutic drug levels to the retinal tissue for up to twelve months from a single IVT injection. We are in the process of assessing clinical development options for once-per-year dosing for the treatment of retinal disease.