Kodiak Sciences aims to give patients an ophthalmic drug with a dose advantage over Regeneron Pharmaceuticals’ blockbuster drug. Preliminary data from a pivotal clinical trial in wet age-related macular degeneration raises questions about whether the Kodiak drug can hit its mark.
The value proposition of Kodiak’s drug KSI-301 is that patients taking it require fewer eye injections than Regeneron’s Eylea, which is dosed every two months. But KSI-301 didn’t meet the study’s primary goal of showing so-called non-inferiority — an effect that was about the same as the comparison treatment, according to a vision test (reading the letters on an eye chart). The Palo Alto, Calif.-based company on Wednesday attributed the failure to the outcome of a “small number of patients.”
In the wet form of AMD, blood vessels leak blood or fluid into the part of the retina called the macula. It is currently treated with drugs that block vascular endothelial growth factor (VEGF), a protein that triggers the growth of blood vessels that causes the disease. Regeneron’s Eylea is an anti-VEGF drug. Kodiak’s drug is an antibody designed to block VEGF. It comes from a technology, the Antibody Biopolymer Conjugate (ABC) platform, that prolongs the duration of a drug in the eye tissue, thereby extending the dosing interval.
In the Phase 2b/3 trial of KSI-301, patients in the Kodiak drug arm began taking it monthly for three months. After that, they were divided into subgroups and treated according to a three-, four- or five-month dosing schedule. The design of the study did not allow for more frequent dosing. For data analysis, subgroups were pooled together and compared to the Eylea group. Kodiak attributed the trial failure to outcomes for some patients in the three-month interval subgroup. For some participants in this subgroup, this dosing interval was insufficient to maintain vision improvement, and vision actually worsened, the company said in a report. Investor introduction.
Kodiak drug is safe and well tolerated by patients. There were no reported cases of eye inflammation or blockage of blood circulation. Despite a phase 2b/3 failure in wet AMD, Kodiak continues to test its drug. In another phase 3 study in wet AMD, patients received monthly doses of KSI-301 — a more frequent dosing regimen than Eylea. The drug is also being evaluated in clinical trials for retinal vein occlusion (administered every two months) and diabetic macular edema (administered every two months).
“It is not sufficient to allow KSI-301 treatment no more than every 12 weeks after each patient’s loading phase,” Kodiak CEO Victor Perlroth said in a prepared statement. “Nevertheless, we believe the results show that demonstrated significant anti-VEGF effects, robust durability, and a reassuring safety profile. We believe these data continue to support the potential of our ABC platform to significantly extend the treatment interval for retinal disease in a safe and convenient manner.”
Investors had a more bleak view on the results. Shares of the company fell more than 80% on Wednesday.
Photos by Flickr users Ken Tigardin through Creative Commons license
