Visual acuity benefit seen with SnET2 photodynamic therapy

August 1, 2004

Fort Lauderdale, FL-The investigational drug tin ethyl etiopurpurin (SnET2) produced a visual acuity benefit and slowed the development of neovascular lesions in two phase III trials of SnET2 photodynamic therapy (PDT) (Miravant Medical Technologies) for the treatment of subfoveal choroidal neovascularization associated with wet age-related macular degeneration, said Edgar L. Thomas, MD, Retina-Vitreous Associates, Los Angeles.

Fort Lauderdale, FL-The investigational drug tin ethyl etiopurpurin (SnET2) produced a visual acuity benefit and slowed the development of neovascular lesions in two phase III trials of SnET2 photodynamic therapy (PDT) (Miravant Medical Technologies) for the treatment of subfoveal choroidal neovascularization associated with wet age-related macular degeneration, said Edgar L. Thomas, MD, Retina-Vitreous Associates, Los Angeles.

"The 0.5 mg/kg treatment regimen gave a consistent visual acuity benefit at all points over the 2-year study," Dr. Thomas said. "The vision benefit was remarkably consistent between the two arms of the study, study 1 and study 2 (p < 0.05), and was highly statistically significant in the pooled data (p < 0.005)."

An important finding was that visual outcome was independent of lesion composition.

Dr. Thomas also noted that other outcomes of SnET2 PDT treatment were reduced fluorescein leakage, a reduction in subsensory retinal detachment, and a demonstrated benefit in all lesion compositions.

Speaking at the Association for Research in Vision and Ophthalmology annual meeting, Dr. Thomas presented data analyses based on the per-protocol population that was the basis for the company's recent new drug application (NDA) submission to the FDA. The population consisted of patients who received the prespecified minimal exposure to the treatment regimen; these patients received at least two treatments during the study and had lesions at baseline within the 3-mm laser spot size.

Two-year follow-upThe two randomized, placebo-controlled, parallel group studies were conducted at 60 U.S. sites. A total of 920 patients received drug or placebo and light treatments and were followed for 2 years. Patients were eligible for re-treatment at 90-day intervals.

Following treatment, visual acuity was measured using the ETDRS eye chart and compared with the baseline measurements. The primary endpoint of the study was the percent of patients losing less than 15 letters on the ETDRS chart. Secondary endpoints included response by letters lost and dynamic measurements of lesion parameters.

Of two drug doses tested, the 0.5 mg/kg was determined to be more effective.

"The preliminary analysis clearly showed a beneficial trend in the 0.5 mg/kg group, although not statistically significant. This trend was supported by the photographic and angiographic data, prompting an evaluation of efficacy and an additional analysis of other sets within the study," Dr. Thomas continued.

Stabilization of visual acuityDuring the study, lesion parameters were measured at the University of Wisconsin Fundus Photography Reading Center, Madison. Dr. Thomas noted that the area of fluorescein leakage in patients who received placebo increased markedly over a 61-week period and declined afterward by natural involution, while treated patients had a statistically significant reduction in leakage at all times relative to placebo. The therapy also produced a marked reduction in subretinal fluid compared with placebo.

"These improvements in lesion characteristics support the stabilization of visual acuity demonstrated by SnET2," Dr. Thomas said.

Data from the trial also provided two other interesting observations, Dr. Thomas explained.

"With our data from this study, this drug has a finite endpoint in number of treatments and a finite endpoint in time," he added. "We found that if you treated three times over 6 months, you got the maximum benefit. This suggests the potential for a clearly defined treatment regimen."

In addition, higher visual acuities at baseline correlated with increased visual benefit.

"Other reports have suggested that PDT benefits patients with lower visual acuity at initiation of treatment. In contrast, in the SnET2 trial, all patients benefited, with the greatest vision benefit in patients with higher visual acuity at baseline," Dr. Thomas said. "This suggests that early intervention can stabilize vision at higher levels without the need for watchful waiting."