Squalamine lactate preserves vision in phase II trial

June 1, 2005

Key Biscayne, FL—In a small, phase II clinical trial of squalamine lactate (Evizon, Genaera Corp.), a systemically delivered drug for the treatment of choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD), all patients who received a 40-mg dose had preserved or improved vision through a 4-month study period, reported Carl Regillo, MD, FACS.

In addition, 90% of eyes treated with a 10-mg dose showed similar outcomes. Each treatment group included six patients (12 eyes) with bilateral wet AMD.

Dr. Regillo, professor of ophthalmology, Wills Eye Hospital and Thomas Jefferson University School of Medicine, Philadelphia, presented pharmacokinetic data and preliminary visual acuity outcomes from the multicenter, open-label trial at the Macula Society annual meeting here. Although the drug was tested at 10-, 20-, and 40-mg doses, data on the 20-mg dose were not available at the February meeting.

Great gains in vision At the 4-month evaluation, the greatest degree of improvement in the 40-mg group was a gain relative to baseline of 18 letters (3.6 lines) on the ETDRS chart. The greatest degree of loss was 12 letters. In the 10-mg group, one patient withdrew after month 2 with a loss of 26 ETDRS letters.

"The vision results did look a little bit better with the 40-mg dose, so there was a suggestion of a dose-response relationship," Dr. Regillo said.

He also noted that many patients had some degree of visual improvement in the fellow eye as well as the study eye, which was important because the fellow eyes in these patients had more advanced, late-stage disease. "We would not have expected those eyes to have improved in any way, yet showing some improvement was suggestive of a possible biological effect," he added.

This study was primarily designed to gather pharmacokinetics data, which showed that squalamine lactate was rapidly cleared from the plasma following infusion, Dr. Regillo said. Results from the six patients in the 40-mg group suggest that squalamine lactate undergoes biphasic elimination from the circulation with a terminal half-life of about 7 hours.

However, because the drug works at the intracellular level, it may have a longer biologic effect than the pharmacokinetics data suggest.

"The drug doesn't accumulate in the system per se from a pharmacokinetics standpoint, but it appears to have a sustained therapeutic effect as best as we can tell at this point," Dr. Regillo explained.

He added that although the study was short-term and open-label, the safety profile was excellent, and the drug is being tested in additional studies. The largest is designed to evaluate the safety and efficacy of squalamine lactate in 100 patients with wet AMD over a 2-year period. Enrollment in this phase II multicenter, double-masked, controlled study is ongoing.

As an anti-angiogenic drug, squalamine lactate is also being studied as a cancer treatment, although most of Genaera's efforts have focused on its potential as a therapeutic agent for AMD.

In theory, squalamine lactate and several other drugs such as Genentech's bevacizumab (Avastin) and ranibizumab (Lucentis) might be effective against both cancer (particularly solid tumors) and wet AMD because they inhibit abnormal blood vessel growth, Dr. Regillo said.