Integrin antagonist well tolerated, safe for exudative AMD, finds phase I study

May 5, 2009

A small-molecule integrin antagonist (JSM 6427, Jerini Ophthalmic) administered intravitreally to 28 patients in a phase I multicenter open-label study showed a trend toward increased best-corrected visual acuity (BCVA) in patients treated with one dose of the drug. The results were less dramatic in patients who required repeated dosing, said Anthony Capone, MD, clinical associate professor of ophthalmology, Oakland University, Royal Oak, MI.

Fort Lauderdale, FL-A small-molecule integrin antagonist (JSM 6427, Jerini Ophthalmic) administered intravitreally to 28 patients in a phase I multicenter open-label study showed a trend toward increased best-corrected visual acuity (BCVA) in patients treated with one dose of the drug. The results were less dramatic in patients who required repeated dosing, said Anthony Capone, MD, clinical associate professor of ophthalmology, Oakland University, Royal Oak, MI.

The drug appears to be well tolerated and safe, he said.

“Integrin α5β1, the fibronectin receptor, is part of a final common downstream pathway for many angiogenic growth factors and is expressed on many cell types involved in ocular neovascularization,” Dr. Capone said. “[The drug] is a highly potent and specific small-molecule antagonist of α5β1 and in animal models inhibits new choroidal neovascularization (CNV), regresses established CNV, and inhibits ocular and systemic inflammation and fibrosis, making [it] an attractive option for a multipronged therapeutic strategy for the treatment and prevention of pathologic angiogenesis.”

Patients with CNV (31% classic, 38% minimally classic, and 31% occult) received a single dose or repeated intravitreal injections (up to four) of the drug, which has a short half-life and a short interval of intravitreal concentration. Patients (mean age, 78.6 years) had visual acuities from 20/40 to 20/800 at baseline and central retinal thickness on optical coherence tomography exceeding 250 µm. The patients were followed for 1 year.

Patients who received one dose had a history of AMD that was shorter than patients who received more than one dose (2 versus 5 years, respectively), smaller lesions, and less fibrosis in the subretina.

All patients who received one dose of drug showed a trend to increased BCVA; the patients who received repeated doses had less dramatic increases in BCVA. There were no ocular adverse events or drug-related adverse events. There were four non-ocular side effects that were not considered to be drug-related. There was one case of transient electroretinography changes after the fourth injection that reversed after 7 days. The repeated dose cohorts completed enrollment and are in early follow-up. A sustained-release formulation of the drug is under development.