Topical Ophthalmic Treatment for Neovascular Age-related Macular Degeneration (nAMD)

Project Summary The long-term goal of this application is to clinically develop and commercialize topical ophthalmic products to treat neovascular Age-related Macular Degeneration (nAMD). nAMD is the leading cause of vision loss among the elderly, with approximately 200,000 new cases diagnosed each year in the US. The prevalence of nAMD is expected to more than double from 2.1 million in 2010 to 5.4 million by 2050. Patients with nAMD experience abnormal neovascularization in sub-retinal tissues, leading to retinal detachment and loss of visual acuity. Therefore, inhibiting neovascularization is a validated approach to treating nAMD. Existing treatments primarily involve monthly or bimonthly intravitreous injections (IVTs) of VEGF inhibitors, such as Lucentis® and Eylea®. These injections, although effective, pose significant challenges, particularly for the elderly, who experience discomfort and difficulty during injections. This highlights a pressing need for an accessible home-based topical treatment option. The IVTs of VEGF inhibitors can lead to potential complications such as scarring, fibrosis, or atrophy in the back of the eye when injections are repeated over several years, which can lead to drug resistance or loss of visual acuity. To maximize visual acuity retention, patients should receive less invasive treatments, such as topical applications, and visit their ophthalmologist regularly. Depending on disease status and progression, ophthalmologists might adjust the dosing frequency of a topical product to minimize the potential complications of VEGF inhibitors. However, previous attempts at topical treatments have failed, largely due to poor delivery of the active pharmaceutical ingredients (APIs) to the sub-retinal tissue and safety concerns. This became a significant hurdle in development. Our compound, AMD101 (rifampicin), repurposed from its original use as an oral antibiotic, has shown promising preclinical results in inhibiting neovascularization, with an effective dose significantly lower than its antibacterial dose. This specificity is crucial in minimizing systemic exposure and potential safety concerns. Our AMD101 topical formulation has enabled efficient delivery to the back of the eye by topical application, potentially revolutionizing treatment for nAMD. Aim 1: Achieve Successful Outcomes in the Pre-IND Meeting. At the pre-IND meeting, development questions related to Chemistry Manufacturing and Controls (CMC), nonclinical and clinical plans, and regulatory strategies will be discussed with the FDA. The feedback provided by the FDA’s Division of Ophthalmology at the pre-IND meeting will be the foundation that validates our development plan and allow us to implement the IND-enabling studies and subsequent IND submission with minimal risks. The IND-enabling studies and IND submission will be proposed in the SBIR Phase II application following the completion of the pre-IND meeting.