Announcement • Jun 09
Oculis Holding AG Announces First Patient Randomized In PREDICT-1 Registrational Trial Of Licaminlimab
Oculis Holding AG announced that the first patient has been randomized in the PREDICT-1 (Personalized dRy Eye Disease Investigational Clinical Trial) genotype-based registrational trial in dry eye disease (DED). PREDICT-1 is the first genotype-based registrational trial in dry eye disease (DED), with the potential of delivering a first-in-class precision medicine treatment in DED. This FDA-aligned trial targets the specific TNFR1 genotype to maximize treatment effects, with approximately 70% of clinical sites already activated and patients in the run-in phase. Licaminlimab has the potential to offer a targeted precision solution for a highly unsatisfied market. The first registrational trial in the program, PREDICT-1, is designed to further evaluate the efficacy of Licaminlimab in DED symptoms and its safety compared with vehicle in patients carrying a specific TNFR1 genotype, while also evaluating the effect in the overall study population. The PREDICT-1 trial is a randomized, multi-center, double-masked, vehicle-controlled study that plans to enroll approximately 160 patients of whom approximately two-thirds will have the specified TNFR1 genotype. The primary endpoint is the change from baseline to Day 29 in the global ocular discomfort severity score in patients with the specified TNFR1 genotype. The same outcome measure will be evaluated in the overall study population as a key secondary endpoint. This precision medicine approach is designed to identify patients more likely to benefit from Licaminlimab. PREDICT-1 incorporates a screening phase. This process is designed to ensure appropriate patient selection based on genotype status assessed prior to the artificial tear run-in phase, as well as ocular discomfort severity (=60 in the global ocular discomfort severity score), evaluated both before and after the run-in phase. TNFR1 is a key receptor mediating TNFa-driven inflammation and apoptosis. Licaminlimab has shown greater clinical response in patients with a specific TNFR1 genotype in Phase 2 trials, with substantial improvements in signs and symptoms. These findings are consistent with the literature suggesting that genetic variation in the TNF/TNFR1 pathway may account for variability in the inflammatory response, and that TNFR1-mediated inflammation may play a key role in ocular surface pathology in DED. The PREDICT-1 trial is designed to leverage these findings with the aim of delivering the first precision medicine treatment in ophthalmology. In the U.S. approximately 10 million diagnosed patients suffer from moderate to severe DED. Current disease management relies on a trial-and-error therapeutic approach, with a minority (approximately 13%) of patients experiencing sustained relief, leading to an 85-90% discontinuation rate within the first 6 months, underscoring the significant unmet need for a targeted, effective treatment approach. Licaminlimab has the potential to transform the current DED treatment paradigm by providing a precision medicine approach with high efficacy, rapid onset of action, and a comfort level similar to artificial tears. Licaminlimab is an anti-TNFa eye drop candidate being developed with a single chain antibody fragment (scFv) technology specifically developed to treat ocular inflammatory diseases. The dual anti-inflammatory and anti-necrotic mechanism of action of TNF-a inhibition has been well-established in inflammatory disorders where the systemic use of TNF-a inhibitors has led to marked improvements in the disease management and treatment outcomes. In Phase 2 trials, Licaminlimab has shown a positive treatment effect on both the signs and symptoms of DED and has been well tolerated. In addition, a genetic biomarker has been identified which showed a five- to seven-fold more pronounced treatment effect with Licaminlimab in patients with a variant in the TNFR1 gene. Licaminlimab is an investigational drug in registrational trial and has not received regulatory approval for commercial use in any country. DED is a multifactorial disease in which ocular surface inflammation plays a central role in sustaining the pathological state. It usually affects both eyes and patients may experience a stinging, burning or scratchy sensation. In addition, some patients experience sensitivity to light, eye redness, difficulty wearing contact lenses, difficulty with nighttime driving, and blurred vision which can greatly affect their quality of life. It is a common condition estimated to impact more than 110 million people in the G7 countries (U.S., U.K., Germany, France, Spain, Italy, Japan). Of the approximately 20 million patients who are diagnosed with DED in the U.S., about half or 10 million are considered to have moderate to severe disease. However, only 13% of DED patients receive prescription treatment, primarily with anti-inflammatory medications and despite available therapies, most patients (87%) don’t feel that their chronic DED is well-managed which highlights a high level of dissatisfaction. Furthermore, 90% of patients discontinued their treatment altogether within one year with the vast majority discontinuing in the first 6 months. Unmet medical needs remain for novel anti-inflammatory treatments which are efficacious, fast-acting and well-tolerated as well as developing targeted therapeutics for specific patient subtypes to improve treatment outcomes for this heterogeneous patient population.
