First results with THR-149 show promise in treatment of diabetic macular edema
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First results with THR-149, a bicyclic peptide inhibitor that targets plasma kallikrein, showed safety and efficacy in treating patients with diabetic macular edema, according to a specialist speaking at the virtual Euretina congress.
“THR-149 is a highly potent, selective and stable peptide developed by Oxurion in partnership with Bicycle Therapeutics. It targets a VEGF-independent pathway, and I truly hope it will be a new treatment modality available to us for treating DME patients, particularly those who don’t respond to anti-VEGF injections,” Francesco Bandello, MD, said.
Plasma kallikrein is a major driver of DME, involved in the cascade of events that lead to retinal vascular permeability, inflammation and angiogenesis. The rationale for targeting plasma kallikrein comes from study data showing that in all patients with DME, the intraocular levels of plasma kallikrein is high, while 30% to 40% of this population do not have increased VEGF levels.
“This is consistent with our clinical experience, where 30% to 40% of DME patients are not responding to anti-VEGF,” Bandello said.
In a phase 1 dose-escalation study, 12 patients were treated using three different doses of THR-149, 0.005 mg, 0.022 mg and 0.13 mg, to test the incidence of side effects, particularly inflammation, and changes in best corrected visual acuity.
“There were improvements in VA, reduction in central subfield thickness and no safety concerns. BCVA increased rapidly following the injection, peaking at 7.5 letters on day 14 with gains maintained at 6.4 letters at 3 months,” Bandello said.
On the basis of these data, the phase 2 KALAHARI trial was conceived and is currently ongoing, involving multiple sites in the U.S. and Europe. It is subdivided into part A for selecting the dose and part B to compare THR-149 with aflibercept. One hundred twenty-two patients with suboptimal response to anti-VEGF therapy were selected, and data are expected to become available in the first part of 2023.
“By using this drug, I hope we will cover all the population of DME patients, also patients who are not sensitive to anti-VEGF,” Bandello said. “My feeling is that it might be useful to combine THR-149 with anti-VEGF to maximize the therapeutic effect. The pathogenic mechanism of DME is multifactorial and complex, and just one approach will never be able to stop the disease.”
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Bandello F. A novel bicyclic peptide inhibitor of plasma kallikrein, THR-149, for the treatment of diabetic macular edema (DME): Clinical and pre-clinical evidence. Presented at: Euretina congress; Sept. 9-12, 2021 (virtual meeting).
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