Squalamine safe, effective when administered with PDT

Indianapolis-Squalamine lactate (Evizon, Genaera) seems to be safe and effective when administered with photodynamic therapy (PDT) using verteporfin (Visudyne, Novartis Ophthalmics/QLT Inc.) to patients with wet age-related macular degeneration (AMD), according to Thomas A. Ciulla, MD.

The adverse events were mild and the drug was well tolerated by the patients. The group that received PDT plus the 40-mg dose of squalamine had the best results compared with the other groups.

Squalamine is an intravenously administered antiangiogenic small molecule with a long intercellular half life and effects, Dr. Ciulla explained. The drug has rapid systemic clearance and an excellent safety profile. It is being evaluated in patients with AMD because it inhibits vascular endothelial growth factor (VEGF) and other growth factors.

The inclusion criteria for the study were standard for a PDT study: the patient had to be eligible to be treated with PDT, the greatest linear dimension of the subfoveal lesions had to be less than 5,400 μm, the area of fibrosis less than 25%, the area of blood less than 50%, and the patients had a visual acuity in the range of 20/32 to 20/200, according to Dr. Ciulla. He practices at Midwest Eye Institute, Indianapolis.

Safety concerns

"The most common safety concern was reactions at the infusion site. Fifteen of 45 patients (33%) had adverse events that were judged to likely be related to the study treatment, and almost all of these were related to infusion site reactions. One patient had a prolonged prothrombin time, which was deemed by the investigator to be probably related to the study treatment. Interestingly, another investigator determined that a retinal detachment was probably related to the study treatment, which is hard to explain mechanistically," he reported.

The patients who received the 40-mg dose received a mean of 6.3 treatments compared with 7.6 treatments for the patients who received the 20-mg dose. The patients who received only PDT were given a mean of 8.8 treatments.

Dr. Ciulla was encouraged by the results.

"Evaluation of the visual acuity at week 29 showed that the PDT only group had a mean loss of visual acuity of 4.8 letters compared with the group that received PDT plus the 20-mg squalamine dose, which had a mean loss of 5.7 letters. The group that received PDT plus the 40-mg dose of squalamine had a mean gain of 0.4 letter. The difference between the PDT control group and the PDT plus 40-mg dose of squalamine was 5.2 letters," he reported.

The difference did not reach significance because of the small sample size and short follow-up. The results in the group that received the 10-mg dose was very similar to the PDT plus the sham treatment group.

A trend toward stabilization of visual acuity was seen in the group that received the 20-mg or 40-mg dose of squalamine plus PDT compared with the group that received PDT only (78%, and 90%, respectively for the 20 mg and 40 mg squalamine plus PDT groups versus 71% in the PDT only group), according to Dr. Ciulla.

Some subjects within the PDT only group had a gain of 15 letters or more; however, 18% in the PDT only group, 20% in the PDT plus 20-mg dose of squalamine group, and 10% in the PDT plus 40-mg dose of squalamine group lost 15 letters or fewer.