Ocular Therapeutix Initiates First Pivotal Clinical Trial in US for Wet AMD
Ocular Therapeutix has initiated its inaugural pivotal clinical trial to assess OTX-TKI, the company's intravitreal implant featuring axitinib, in the treatment of wet age-related macular degeneration (wet AMD). OTX-TKI is also under development for addressing diabetic retinopathy and other retinal diseases.
OTX-TKI is a bioresorbable hydrogel implant under investigation. It integrates axitinib, a small-molecule, multi-target, tyrosine kinase inhibitor known for its anti-angiogenic properties.
"We are thrilled to announce the initiation of our pivotal trial evaluating OTX-TKI for the treatment of wet AMD and look forward to working with clinical sites across the US," said Antony Mattessich, CEO of Ocular Therapeutix. “With the activation of our first clinical site in the US, we believe we are on target to enroll our first subject before year end. The trial is a crucial step forward for our clinical program as we make progress toward our goal of bringing a transformative new treatment that can truly make a difference for wet AMD to patients coping with vision loss."
Ocular Therapeutix has submitted a request for a Special Protocol Assessment (SPA) to the U.S. Food and Drug Administration (FDA) pertaining to the trial's design. This trial is structured as a superiority trial, aiming to enroll around 300 treatment-naïve wet AMD subjects in the study eye. It is a multi-center, parallel-group trial primarily conducted at U.S. sites, with subjects randomized to receive either one injection of aflibercept or one implant of OTX-TKI, followed by supplemental anti-VEGF treatment as needed based on predefined criteria.
The evaluation of OTX-TKI's safety and efficacy will involve measuring best corrected visual acuity (BCVA) and central subfield thickness (CSFT) at the 36-week mark. It's worth noting that even though institutional review board (IRB) approval has been granted, the Company will not initiate subject enrollment until feedback is received from the FDA regarding the SPA.
Dr. Arshad M. Khanani, MD, MA, FASRS, Director of Clinical Research at Sierra Eye Associates in Reno, Nevada, has agreed to serve as the principal investigator for the pivotal Phase 3 trial of OTX-TKI. Dr. Khanani is an internationally recognized retina specialist with extensive experience in designing clinical trials for age-related macular degeneration treatment. He has previously served as a principal investigator in numerous clinical trials focused on assessing innovative treatments for wet AMD and other retinal diseases.
“Anti-VEGF agents have revolutionized the treatment of wet AMD, but numerous real-world patients experience vision loss due to their inability to adhere to the demanding treatment regimen involving frequent injections,” said Dr. Khanani. “OTX-TKI has shown the potential to reduce treatment burden while maintaining vision and anatomy for patients with wet AMD. The OTX-TKI pivotal trial design is unique as it is based on the latest FDA guidance for wet AMD. As a field, we must continue to push for the approval of new therapies while making sure we appropriately manage our patients who participate in these clinical trials. I look forward to working with Ocular Therapeutix, the regulatory agency and the retina community to harmonize regulatory endpoints with clinical practice.”
About the Pitoval Trial
The initiation of the pivotal trial was based on the previously disclosed positive 12-month top-line results from the Company's Phase 1 trial of OTX-TKI in the United States, which involved 21 subjects and focused on treating wet AMD. These trial findings were presented at the Clinical Trials at the Summit 2023 Meeting held in Park City, Utah, in June 2023.
During this trial, individuals who received a single OTX-TKI implant experienced an impressive 89% reduction in treatment requirements compared to those treated with aflibercept. This reduction in treatment burden was achieved while maintaining visual acuity and retinal thickness over the course of 12 months. Specifically, in the OTX-TKI group, there was an average change of -1.0 letters in best-corrected visual acuity (BCVA) and +20.2 μm in central subfield thickness (CSFT) at the 12-month mark. These changes were comparable to the mean alterations observed in the aflibercept group, which showed +2.0 letters and -2.2 μm from baseline, respectively. Furthermore, 60% of OTX-TKI subjects remained free from the need for rescue treatments up to 12 months.
As of the data cut-off date on April 14, 2023, there were no observed drug-related ocular or systemic serious adverse events in the OTX-TKI arm throughout the 12-month duration of the trial.
Dr. David Brown, MD, FACS a renowned leader in the retina community, serves as the co-chairman of the medical leadership board at Retina Consultants of America (RCA), an organization that has confirmed its participation in the trial. Dr. Brown has pioneered research and treatment in retina, boasting a prolific portfolio of over 300 national meeting presentations, abstracts, and scientific papers. His contributions include seminal papers that played a pivotal role in establishing the efficacy of anti-VEGF agents for addressing AMD, diabetic retinopathy, and retinal vein occlusion.
“This pivotal trial is thoughtfully designed to satisfy the FDA’s latest guidance in wet AMD, while also balancing the needs of subjects who enter it,” said Dr. Brown. “The sites at RCA are excited to be a part of the OTX-TKI program as we continue our mission to develop better treatments for patients in the fight against retinal blindness.”
