Novel anti-VEGF antibody biopolymer conjugate safe, effective in early phase 1b results
CHICAGO — Multiple intravitreal administrations of KSI-301, a novel anti-VEGF antibody biopolymer conjugate, improved best corrected visual acuity and retinal anatomy in patients with wet age-related macular degeneration, diabetic macular edema and retinal vein occlusion, a speaker said here.
“Antibody biopolymer conjugates, or ABCs, are a new scientific approach and design platform for intravitreal drugs. KSI-301 from Kodiak Sciences has achieved its early development goals of demonstrating strong efficacy and excellent safety in major retinal vascular diseases,” Pravin U. Dugel, MD, said at the American Society of Retina Specialists meeting.
The phase 1b, open-label study design will include 90 patients randomized 1:3 to receive either KSI-301 2.5 mg or 5 mg. Patients receive three initial injections of KSI-301 4 weeks apart and patients will be evaluated for the need for additional KSI-301 doses at 4-week intervals beginning at week 16. Enrollment for the study is ongoing, Dugel said.
Dugel shared current 12-week data from the study. Seventeen wet AMD patients experienced an 8 ETDRS letter improvement and a 96 µm central subfield thickness (CST) reduction from baseline to week 12. Eight diabetic macular edema and diabetic retinopathy patients experienced a 9.5 letter improvement and a 197 µm CST reduction from baseline. Finally, 10 retinal vein occlusion patients experienced at 26.5 letter improvement and a 209 µm CST reduction from baseline, he said. Antibody polymer conjugates (ABC) are designed for increased durability and efficacy. The ABC platform consists of an antibody and biopolymer covalently bound via single-site specific linkage. The KSI-301 molecule has a higher molecular weight of 950 kDa compared with 26 kDa for brolucizumab, 48 kDa for ranibizumab and 115 kDa for aflibercept.
“This is a large molecule ... importantly, the equivalent ocular concentration at 3 months is a million times that of ranibizumab,” he said.
“Multiple-dose exposure to KSI-301 is well tolerated with no intraocular inflammation in 181 doses,” Dugel said. – by Robert Linnehan
Reference: Dugel PU. Results From a Phase 1B Multiple-Dose Study of KSI-301: A Novel Anti-VEGF Antibody Biopolymer Conjugate (ABC) With Extended Durability. Presented at: American Society of Retina Specialists annual meeting; July 27-30, 2019; Chicago.
Disclosure: Dugel reports he is a consultant to Kodiak Sciences.