The company will move the highest dose of THR-149 (0.13mg) into Part B of the study based on favorable safety profile and positive efficacy data.
Oxurion NV has announced positive data from Part A of its Phase 2 KALAHARI study of THR-149, a plasma kallikrein inhibitor, for the treatment of DME.
Based on these data, Oxurion has decided to move the highest dose of THR-149 (0.13mg) into Part B of the study, which is expected to begin shortly.
THR-149, is being developed as a potential new standard of care intravitreal (IVT) therapy for the 40-50% of DME patients showing suboptimal response to anti-VEGF therapy. THR-149 acts through inhibition of the plasma kallikrein-kinin (PKaI-Kinin) system, a validated VEGF-independent target for DME.
Arshad M. Khanani, MD, MA, director of Clinical Research at Sierra Eye Associates, Reno, Nevada, said in a statement he was glad to see the results from Part A of the KALAHARI study, which was conducted in patients who have shown suboptimal response to anti-VEGF therapy.
“These patients currently have limited treatment options, and the mean BCVA gains of + 6.1 letters at 3 months with stable CST in patients treated with the highest dose of THR-149 is encouraging,” Khanani said. “I am looking forward to recruiting patients into Part B of this trial. I am hopeful that the KALAHARI study will demonstrate that THR-149 could benefit the 40% to 50% of DME patients who respond suboptimally to anti-VEGFs."
According to the company, the Phase 2 KALAHARI study is a two-part, randomized, prospective, multi-center study assessing multiple injections of THR-149 in DME patients who have previously shown a suboptimal response to anti-VEGF therapy. The endpoints of Part A of the study were safety (n = 23) and efficacy (n = 20).
In Part A of the study, three dose levels of THR-149 (0.005mg, 0.022mg and 0.13mg), each administered in three monthly IVT injections, were evaluated in order to select the best dose for Part B of the study.
Results from Part A showed that all dose levels of THR-149 had a favorable safety profile, with no serious adverse events being observed. All adverse events in the study eye were mild to moderate in intensity and no severe ocular adverse events were reported.
Finally, no inflammation was seen in the study eye of any patient at any dose evaluated in Part A of the study.
When assessing efficacy, 3 IVT injections of THR-149 (0.13mg) delivered the most promising results in terms of Best Corrected Visual Accuity (BCVA), the primary endpoint for registration in DME, and also delivered a stable Central Subfield Thickness (CST), a promising result in a population were if left untreated CST would be expected to deteriorate.
Additional results also found:
No patients in the high dose group (n = 8) required rescue medication.
In terms of BCVA, the highest dose delivered a mean 6.1 letter improvement at Month 3. The range of BCVA changes with the highest dose was -0.4 to 12.6 letters at Month 3.
In terms of CST, the highest dose showed a stable CST (mean change of 13 µm) at Month 3. The range of CST changes with the highest dose was -37.1 to 63.6 µm at Month 3.
Oxurion said in its news release that it intends to present a more complete data set from Part A of the KALAHARI study at an upcoming leading ophthalmology conference.
Based on the data, the company will start Part B of the study which will enroll just over one hundred patients who have previously shown a suboptimal response to anti-VEGF therapy, and where THR-149 will be evaluated against aflibercept, the current standard of care, as the active comparator.
According to Tom Graney, CFA, CEO of Oxurion, the positive data from Part A of the KALAHARI study provides proof of concept for multiple injections of THR-149 in this important DME patient population and is a significant de-risking event for the company.
“We are pleased to be able to proceed into the second part of the study, where we hope to confirm THR-149’s ability to address the significant unmet need in this patient population that experiences a suboptimal response to anti-VEGFs and currently lacks adequate treatment options,” he said. “These very encouraging results with THR-149, alongside the initiation of our Phase 2 (“INTEGRAL”) study with THR-687, a pan-RGD integrin antagonist, being developed as a potential first line therapy for DME patients, gives Oxurion one of the most exciting pipelines in ophthalmology today.”
Final topline results from the KALAHARI study are expected by mid-2023.