Trabodenoson on trabecular meshwork rejuvenation: a comprehensive review of clinical data

Trabodenoson is an adenosine mimetic acting selectively at the A1 receptor (A1R) subtype, involved in multiple signaling pathways including matrix metalloproteinase (MMP-2) associated with glaucoma pathological processes. It has been developed as a Phase 3 candidate for the treatment of patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH).

This review summarizes the molecular traits of Trabodenoson in intraocular pressure (IOP) regulations and provides a scientific interpretation of the Phase 2 clinical study results. This article sheds light on the root causes of the two pivotal Phase 3 clinical trial failures in patients with POAG or OH; it further highlights the discovery of MMP-2 in trabecular meshwork (TM) rejuvenation, which has strategic importance in long-term glaucoma patient care.

Trabodenoson is a BID glaucoma eye drop with a possible QD dose as maintenance. Its Phase 3 pivotal clinical trials failed at the wrong dose and dosing regimen because of the misinterpretation of the complex IOP results from the Phase 2 monotherapy and combination studies. The future development should focus on the TM benefits whilst unleashing its potential of neural protection through nanoparticle eye drops, medical coating, and sustained release drug delivery.