Dr. Arshad M. Khanani reviews the Phase 2 part A results of the KALAHARI study of THR-149 for the treatment of DME.
At the 2022 Angiogenesis, Exudation and Degeneration meeting hosted by Bascom Palmer, Arshad M. Khanani, MD, MA, presented his talk, “Phase 2 Results of THR-149 in Patients with DME: KALAHARI Study Part A.”
David Hutton: I'm David Hutton of Ophthalmology Times with our coverage of the Bascom Palmer Eye Institute's 19th Annual Angiogenesis, Exudation and Degeneration 2022, virtual edition. Arshad Khanani, MD, presented data on part A of the KALAHARI trial. Thank you for joining us today. Tell us about your presentation.
Dr. Khanani: Thanks for having me here, David. At Angiogenesis, I presented the results of the part A of the Phase 2 KALAHARI study looking at efficacy of THR-149 In patients with diabetic macular edema.
THR-149 is a highly potent plasma kallikreininhibitor that is designed for DME. P-kal is clinically validated target for edema inflammation and prevention of micro hemorrhages, and we know that P-kal is a key driver in patients with DME, in a subset of patients independent of VEGF. So THR-149 is a selective P-kal inhibitor having the potential to treat 40 to 50% of patients with DME that have suboptimal response to anti-VEGF treatment.
Looking at the study design, this study included patients with suboptimal response to prior anti-VEGF and who can benefit from new mechanism of action. They had to have CST of greater than equal to 320 microns as well as visual acuity between 39 and 73 letters. They had to receive an aflibercept injection three to six weeks prior to screening, and if they met the criteria, they're enrolled in the study.
The part A of the study was dose selection for THR-149. Here we had three different doses: 0.01 milligram, 0.04 milligram and 0.13 milligrams, and patients receive three injections once a month—so day one, month one, and month two—and then the dose level selection for part two was done a month after the last dose.
Here are the results. We found that the multiple intravitreal injection up to three injections of THR-149 were safe and well-tolerated in all treatment groups. There was no events of intraocular inflammation. Also, we found that in the high-dose group, which is the dose that has been selected to go forward, we saw mean BCVA gain of 6.1 letters at month three with gains observed up to six months, as well as CST stabilization over the six-month study period compared to baseline.
Remember that after the three doses, patients were followed, and not treated up to six months in this part A.
There was no need for rescue treatment in the high dose. Also a postdoc analysis was done by the reading center, and what they looked at was the inclusion criteria on imaging and excluding two subjects with abnormalities and OCT. A mean gain in BCV of 9.3 letters was observed at month three in the high dose group, and it was maintained up to month six.
And so based on the results of the Part A, the high dose of THR-149 was selected for the part B of the KALAHARI study. Part A learnings have been implemented in Part B using an amended study design, and part B is currently enrolling globally. So we are looking forward to have the Part B of the trial enrolled and have data in the near future. Thank you for having me here, David.
Note: This transcript has been lightly edited for clarity.