TOP1630 (ophthalmic solution) produced compelling results in Phase 1/2a proof of concept study in the treatment of dry eye disease (DED). TOP1630 improved multiple symptom and sign endpoints in both an environmental setting and in the Controlled Adverse Environment (CAE®; Ora, Inc.) challenge. Furthermore, TOP1630 demonstrated excellent safety and placebo-like tolerability and comfort profiles, unlike currently marketed products.
The most common eye disease, DED is a chronic inflammatory disease characterised by eye dryness and which can have a significant impact on the quality of life of a sufferer. There remains a major unmet medical need for more effective treatments, as currently available treatments for DED have limited efficacy (particularly over the long-term), provide only symptomatic improvement and or are associated with safety and tolerability issues, such as burning or stinging, on instillation that limit their use. Please see our Disease Focus section for more information on the disease.
Better by design
TOP1630 has been designed to deliver long-term efficacy, improving both signs and symptoms of DED by effectively treating the underlying inflammation. It targets several important kinases (P38, Src family kinases (Src & Lck) and Syk) involved in the signalling cascade in inflammatory diseases. TOP1630 has demonstrated an excellent activity profile in vitro and in vivo, including in models of human disease, and it has been shown to synergistically inhibit key pathways involved in innate and adaptive immunity.
TOP1630 has been designed to act locally at surface of the eye, where the inflammation occurs, following topical delivery using eye drops. When administered as an eye drop, the drug is taken up and retained by the target inflammatory cells but otherwise has low bioavailability which, together with the natural physiology of the eye, means that the rest of the body is unlikely to have a significant exposure to the drug. This reduces the likelihood of use-limiting side-effects occurring, as commonly seen with currently available treatments, allowing TOP1630 to be used as an effective long-term treatment.
TOP1630 recently completed a successful Phase 1/2a proof-of-concept (POC) study in DED patients in the US. In the study, TOP1630 delivered statistically significant results across multiple signs and symptoms endpoints in DED starting at day 15, the first study assessment point. All analyses reported are pre-specified, (i.e., no post hoc or subgroup analyses). Symptoms showing significant improvements for TOP1630 versus placebo included improvement in worst DED symptom (diary, p=0.03), ocular discomfort (p=0.02 CAE only), grittiness/foreign body sensation (on four independent assessment scales, each p<0.05) and ocular pain (p=0.02). Total ocular surface (all regions), corneal sum and conjunctival sum staining improved with TOP1630 compared to placebo (each p<0.05).
Importantly, there were no safety findings, with TOP1630 shown to be safe and very well tolerated with a placebo-like profile. Importantly, this included no noticeable instillation site pain and discomfort.
TopiVert intends to seek an industry partner to complete the development of TOP1630 beyond the current POC study and to undertake the global commercialisation of the product.