Oxurion kick-started 2020 with positive topline data from phase 1 clinical trial evaluating THR-687 for treatment of DME. This molecule showed a rapid onset of action across all doses after just one injection. Improvement was observed in vision, measured by best corrected visual acuity (BCVA), and macular swelling, measured by central subfield thickness (CST) on OCT (optical coherence tomography). “The positive phase 1 data indicates that THR-687 could potentially be an effective therapy for patients with DME”, notes Arshad Khanani, M.D., M.A..
THR- 687, a pan-RGD integrin antagonist, has broad therapeutic potential. This compound can target multiple disease hallmarks of diabetic retinopathy (DR), with and without DME, and also with wet age-related macular degeneration (AMD).
Preclinical models show that THR-687 is a potent inhibitor of angiogenesis induced vascular leakage. The inhibition of integrins targets multiple processes involved in pathological angiogenesis and vascular leakage for common retina pathologies. An integrin antagonist drug has the potential to block several pathways, and as such reduces the expression of growth factors as well.
Set-up & safety
The phase 1 study evaluated safety and tolerance of a single injection of THR-687 in 12 patients with DME with a history of response to prior anti-VEGF, corticosteroid treatment or laser. Each patient received one of three doses: 0.4 mg (3 patients), 1 mg (3 patients) and 2.5 mg (6 patients). All 12 patients completed the study, with no dose-limiting toxicities or serious adverse effects reported.
In each dose group, there was one subject with a non-serious adverse event that was deemed to be related probably to the injection procedure. Otherwise, there were a few other side effects likely due to disease progression or concomitant diseases. In total, 9 adverse events were reported in 5 subjects. Three of them received rescue therapy.
Immediate vision improvement
At day 1 an immediate improvement in vision was found. The overall mean change in BCVA was rather modest at day 1 with 3.1 letters gained, but at day 7 it was already 7.2 letters. The highest mean change was reported at month 1 with 9.2 letters gained. Most impressively, this improvement was mostly maintained post-single injection at month 3 with a mean overall gain of 8.3 letters.
Overall, a marginal impact on mean CST was noted up to month 1, followed by an increase until month 3.
THR-687 could potentially be an effective therapy for patients with DME.
– Arshad Khanani, M.D., M.A.
A pronounced dose response is observed for this single injection of THR-687. Patients receiving the highest dose (2.5 mg) noted an improvement in BCVA of 12.3/12.5 letters at month 3.
A mean CST decrease of 106 µm was reported at day 14 in the highest dose group.
This makes THR-687 a promising candidate for the treatment of vision-threatening eye diseases such as DME and wet AMD. Potentially, it could become a standard of care for all DR patients, with or without DME, and wet AMD patients based on its broader biological effect than anti-VEGF therapy.
On track to start phase 2 clinical trial
“I am very encouraged to see excellent signs of efficacy so quickly post-treatment. The study also demonstrated that THR-687 had a rapid positive effect on best corrected visual acuity (BCVA) that was durable for up to 3 months after just a single injection. This promising initial data indicate that THR-687 could potentially be an effective monotherapy for patients with DME”, says Dr. Arshad Khanani.
Patrik De Haes, M.D., CEO of Oxurion, said: “These encouraging findings from our phase 1 clinical trial with THR-687, along with the very positive feedback we have received from the retinal community, high – light the significant potential of this novel integrin antagonist. We are on track to start a phase 2 clinical study with THR-687 in treatment-naïve DME patients in H1 2021.”