Oxurion NV (Euronext Brussels: OXUR), a biopharmaceutical company developing next generation standard of care ophthalmic therapies, with a clinical stage portfolio in vascular retinal disorders, announced updates on its two clinical programs, THR-687, initially being developed for first line treatment of DME, and THR-149 being developed for second line treatment of DME.
THR-687 – Completed Patient Enrollment for Part A of the Phase 2 Clinical Trial (“INTEGRAL”) Evaluating THR-687 in Patients with DME
THR-687 is a potential best-in-class small molecule pan-RGD integrin antagonist being developed for the treatment of DME and holding promise for the treatment of wet Age-related Macular Degeneration (wAMD) and macular edema following Retinal Vein Occlusion (RVO). The INTEGRAL trial is a two-part Phase 2, randomized, multi-center clinical trial and is the first trial in which multiple intravitreal injections of THR-687 will be administered in humans.
“We are pleased to announce the completion of patient enrollment for Part A of the Phase 2 INTEGRAL trial of THR-687,” Tom Graney, CFA, Chief Executive Officer of Oxurion commented. “The rapid enrollment in this trial is a testament to how interested physicians and patients are to have a new mechanism of action with the potential to offer improved efficacy over the standard of care anti-VEGF therapy. This milestone brings us closer to delivering a potential first line treatment of choice for patients with DME. With its unique mechanism of action, THR-687 demonstrated promising results in its Phase 1 study, which showed an encouraging efficacy signal following just a single dose. This best-in-class small molecule has further potential to be developed to raise the standard of care in additional significant indications, including wAMD and RVO.”
Part A of the trial will assess two dose levels of multiple THR-687 injections and, if successful, the trial’s results will be used to select the appropriate dose for Part B of the INTEGRAL trial that will evaluate the efficacy and safety of THR-687 versus aflibercept (the current standard of care) for the treatment of DME. Part B of the trial will include both treatment experienced and treatment naïve subjects.
The dose selection decision, following Part A, is anticipated in the first half of 2022 with top line data from Part B expected in the second half of 2023.
THR-149 – Received Approval from the US Institutional Review Board (IRB) to Amend the Protocol for Part B of the Phase 2 Clinical Trial (“KALAHARI”) Assessing THR-149 versus aflibercept for Treatment of DME
THR-149 is a potent plasma kallikrein inhibitor being developed as a potential new standard of care for the 40-50% of DME patients showing suboptimal response to anti-VEGF therapy.
The trial’s U.S. IRB has approved a protocol amendment to Part B of its ongoing KALAHARI trial assessing multiple doses of THR-149 versus aflibercept for the treatment of DME. The changes to the protocol are designed to:
Enhance the probability of a successful trial outcome without impacting the trial timelines by refining the patient inclusion/exclusion criteria, and
Provide preliminary data on the use of THR-149 before, or immediately following, anti-VEGF therapy by exploring synergies of THR-149 with aflibercept utilizing a cross-over style design with a fourth injection at month four
In September 2021, Oxurion announced positive data from Part A of the Phase 2 KALAHARI trial evaluating THR-149 for the treatment of DME. These data demonstrated that THR-149 had a favorable safety profile, with no serious adverse events or inflammation observed at any dose level. The high dose achieved a mean improvement in Best Corrected Vision (BCVA) of 6.1 letters at Month 3 without the need for rescue medication. BCVA is the primary endpoint for registration in DME trials.
The post-hoc analysis of the Part A results identified opportunities to optimize the inclusion and exclusion criteria for Part B for both probability of success and speed. Part B of the KALAHARI trial is ongoing, assessing three monthly injections of THR-149, compared to three monthly injections of aflibercept, up to Month 3. As from Month 3, the safety and efficacy of a switched fourth injection (THR-149 to aflibercept or aflibercept to THR-149) will be evaluated in about half of the subjects whereas in the other half of the subjects the durability of three monthly injections (THR-149 or aflibercept) will be evaluated through a single sham injection. The trial is planned to randomize approximately 108 subjects in Part B and the primary endpoint remains the mean change in BCVA letter score from baseline, at Month 3.
Tom Graney, CFA, Chief Executive Officer of Oxurion, said, “I am pleased that the IRB has approved our protocol amendments to Part B of the Phase 2 KALAHARI trial. These amendments, including refining the patient inclusion and exclusion criteria, have been made based on further post-hoc analyses of the data from Part A of the trial, which have improved our understanding of which patients are most likely to respond to treatment with THR-149. We believe these changes will maximize our ability to achieve a successful trial outcome while preserving the benefits of the initial trial design and maintaining our timelines.”
Additional new data from Part A from the KALAHARI trial will be presented at Angiogenesis, Exudation, and Degeneration 2022, a virtual conference taking place February 11 and 12, 2022. Arshad M. Khanani, M.D., M.A., Director of Clinical Research at Sierra Eye Associates, Reno, Nevada, US will present the Part A data on February 12th.
Final topline results from Part B the KALAHARI trial are expected by mid-2023.