Kodiak Sciences’ anti-VEGF drug improved vision and reduced retinal thickening in patients with three diseases of the retina in a phase 1b study, results of which were presented this weekend at the annual meeting of the American Society of Retina Specialists (ASRS). The drug is on track to enter a phase 2 study in wet age-related macular degeneration (AMD) in the third quarter.
Vascular endothelial growth factor (VEGF) is not a new target in eye disease—it is, after all, the target of Regeneron and Bayer’s blockbuster Eylea, which is approved for all three of the diseases Kodiak looked at in the phase 1b study. Eylea, a drug that’s injected directly into the eye can be—understandably—unappealing to patients. This is where Palo Alto, California-based Kodiak thinks it has an advantage.
Eylea and Kodiak’s KSI-301 are both anti-VEGF biologics. They work by blocking VEGF to prevent the growth of leaky blood vessels in the eye. But KSI-301 has an extended ocular half-life, meaning it sticks around in the eyes for longer, which would allow patients to go longer between injections. The hope is that more patients will continue with treatment if injections are less frequent.
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The phase 1b study tested KSI-301 in patients with AMD, diabetic macular edema (DME) or macular edema stemming from retinal vein occlusion (RVO). The growth of leaky blood vessels in the eye leads to retinal scarring and the death of photoreceptors, hallmarks of wet AMD. Macular edema is the buildup of fluid in the macula, which is in the center of the retina. The swelling of the macula leads to distorted vision. RVO is swelling caused by the blockage of veins in the retina, while DME is a consequence of diabetic retinopathy, a complication of diabetes in which high blood sugar damages the retina’s blood vessels.
So far, the phase 1b study has enrolled 77 patients who will receive a total of three monthly doses of KSI-301. The investigators will follow patients, who will receive one of two dose levels, for seven months after treatment. The data reported Saturday come from 35 patients who reached the 12-week mark as of July 24.
“Across all three diseases under study, strong improvements in vision and retinal anatomy were observed over 12 weeks,” the company said in a statement.
Changes in vision were measured by Best Corrected Visual Acuity—the best vision a person can achieve wearing glasses or contact lenses using a standardized eye chart—and changes in retinal anatomy were measured by the thickness of the retina at its center. All three patient groups saw improvements on both metrics, but the RVO patients showed the most progress, reading a median of 26.5 more letters on an eye chart and logging a median 209-micron decrease in retinal central subfield thickness after treatment.
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"In addition to vision and anatomic improvements, we have observed encouraging signs of disease modification,” said Kodiak Chief Medical and Chief Development Officer Jason Ehrlich, M.D., Ph.D., in the statement.
The investigator presented a handful of case studies at the meeting, including an RVO patient whose blood flow in the retina returned to normal a week after the first dose and a DME patient whose disease became less severe.
“In a DME patient with proliferative retinopathy, we observed conversion to non-proliferative retinopathy and a two-step improvement in diabetic retinopathy severity score at the 12-week assessment,” Ehrlich said. Translation? Before treatment, that patient’s retina had started growing—proliferating—new blood vessels, and after treatment, it stopped.
The study reported no serious drug-related side effects, with the mild side effects recorded being par for the course for anti-VEGF drugs injected into the eye.
KSI-301 is slated to start a phase 2 study in wet AMD later this year. Last September, Kodiak raised $90 million in its Nasdaq debut, falling short of its proposed $100 million IPO. The funds are to bankroll the phase 1b study through completion and to get the drug into phase 2 studies in DME and diabetic retinopathy as well as in wet AMD.