Enrollment complete for Phase II clinical study for treating DME
THR-317, an anti-placental growth factor (anti-PlGF) with a mechanism to act against hyperpermeability, is being developed to increase the efficacy of standard of care therapy and decrease the treatment burden for patients with DR and DME. By reducing leakage of blood vessels, it can halt early-stage inflammation in NPDR and prevent further progression of edema, angiogenesis and fibrosis. Since anti-PlGF also tackles fibrosis and inflammation, it also has the potential to treat PDR patients if used in combination with anti-VEGF therapy with alternating injections.
Oxurion has recently reported topline month 3 results of the Phase 2a clinical study to investigate the efficacy and safety profile of THR-317 in combination with anti-VEGF (Lucentis®) for the treatment of diabetic macular edema (DME).
Oxurion is also evaluating THR-317 as a potential first-in-class treatment for idiopathic macular telangiectasia type 1 (MacTel 1) in a Phase II clinical trial.
We need therapies fighting different hallmarks of diabetic eye disease simultaneously
- Alan Stitt, Professor, Dean of Innovation & Impact and the McCauley Chair of Experimental Ophthalmology
Clinical study evaluating THR-317 (anti-PlGF) for treatment of Idiopathic Macular Telangiectasia Type 1 (MacTel1)
Ongoing, first patient enrolled
This Phase 2 study (THR-317-003 - NCT03669393), an open-label multi-centre study, plans to enrol 10 patients with macular edema caused by MacTel 1, who will each receive 3 intravitreal THR-317 injections over a period of 2 months. Efficacy and safety of the therapy will be assessed via functional and anatomic endpoints.
This clinical trial is being conducted in line with the Oxurion strategy and mission to expand its focus on developing treatments for other back of the eye diseases, in addition to its novel diabetic eye disease pipeline.
To be expected mid-2019
Clinical study evaluating THR-317 (anti-PlGF) in combination with anti-VEGF (ranibizumab) for treatment of DME
Ongoing, enrollment complete
The Phase II clinical study (THR-317-002) evaluates the safety and efficacy of IVT THR-317 along with ranibizumab, compared with ranibizumab monotherapy in patients with DME.
Patients will be randomized into either a combination arm of THR-317 (8mg) + ranibizumab, or ranibizumab plus a sham administration. The main outcome measure will be change from baseline in best corrected visual acuity (BCVA) at month 3.
Seventy patients have been enrolled: half anti-VEGF treatment naïve, half sub-optimal responders to prior treatment with ranibizumab.
Topline month 3 results available
A single-masked, multicenter study to evaluate the safety and efficacy of anti-PlGF (THR-317) for treatment of DME
The THR-317-001 study enrolled a total of 49 patients and included anti-VEGF treatment naïve patients (N=40) and anti-VEGF sub-optimal responder patients (N=9).
The study met its primary endpoint of safety for both the 4 mg and 8 mg doses. There was a low incidence of ocular adverse events, which were mostly mild and related to the injection procedure.
While the study's focus was safety, efficacy was also observed. Overall, patients receiving the 8mg dose of THR-317 achieved better visual acuity outcomes than those in the 4mg dose group. Initial data reported for the 8mg anti-VEGF treatment naïve group at Day 90 (30 days after the last THR-317 injection) showed that 30% of patients achieved a ≥ 15 letter vision gain from baseline.
At Day 150 (90 days after the last THR-317 injection), 30% of patients in the 8 mg anti-VEGF treatment naïve group showed ≥ 10 letter vision gain and 10% a ≥15 letter vision gain, supporting durability of effect.
In the 8mg group, average change from baseline in central subfield thickness showed a positive trend at Day 90, not observed at Day 150 (90 days after last injection).
The study also showed clinical activity in the THR-317 anti-VEGF sub-optimal responder group. Due to the small numbers in this group, no firm conclusions could be drawn.
These data provide continued support to development of THR-317.
Presentation of THR-317-001 study results is planned for an upcoming ophthalmology meeting.
In preclinical models, anti-PlGF has been shown to be anti-inflammatory while having anti-angiogenic and anti-edema properties.
Non-clinical experiments indicate that anti-PlGF in the presence of an anti-VEGF antibody has an additive effect inhibiting the growth of new blood vessels, a disease hallmark of DME (Van de Veire et al., 2010). This may mean that a combination approach could produce a better treatment response. The anti-PlGF component might offer the advantage of reduced inflammation associated with a lower level of PIGF (van Bergen et al., 2017).
Publication of preclinical data in Experimental Eye Research: "Neutralization of placental growth factor as a novel treatment option in diabetic retinopathy"