ISTA Pharmaceuticals, Inc. reported preliminary efficacy and safety results for two Phase III clinical trials of a single injection of Vitrase for the treatment of severe vitreous hemorrhage. Data from the two Phase III studies did not show a statistically significant improvement in the primary (surrogate) endpoint. However, clinically relevant improvements in visual acuity were observed in each of the studies for Vitrase treated patients.
Clinically relevant changes in best-corrected visual acuity (BCVA), a secondary efficacy endpoint, for the 55 IU Vitrase dose were observed in both studies. The study conducted outside North America showed a statistically significant difference for the 55 IU Vitrase dose in the time required to achieve an improvement in BCVA of three or more lines on an eye chart on or before three months following treatment as compared to those receiving placebo treatment.
Additional analysis, not previously defined, showed statistically significant changes in two parameters, BCVA and vitreous hemorrhage density. Specifically, in both studies, a statistically significant improvement in BCVA was shown in the proportion of patients who had an improvement at scheduled intervals, e.g. at one month and two month visits following treatment with the 55 IU dose of Vitrase. These statistically significant findings extended to the three-month post-treatment visit in the study conducted outside North America. Statistically significant improvements in BCVA were not seen with any other doses of Vitrase at the three-month visit following treatment. Additionally, there was a decrease in the density of the vitreous hemorrhage that was clinically meaningful and statistically significant as compared to placebo at the month one, month two and month three visits for patients treated with the 55 IU dose of Vitrase in both studies.
"We intend to meet with the FDA as soon as possible to discuss these results," said Vicente Anido, Jr., Ph.D., ISTA's CEO. "In the meantime, we will continue to thoroughly analyze the data in preparation for our next round of discussions with the agency."
Statistically significant ocular adverse events observed in both studies were iritis, hyperemia and ocular pain, with iritis the ocular adverse event of highest incident. Additionally, in the North America study, other statistically significant ocular adverse events included eye irritation, increased lacrimation, reduced visual acuity, vitreous hemorrhage, photophobia and photopsia.
A total of 1,306 patients were enrolled in one of two randomized, double- masked, placebo-controlled international studies. The 750 patients enrolled in the North American study were assigned to one of four treatment arms (saline injection, 7.5 IU, 55 IU or 75 IU Vitrase injection), while the 556 patients treated in the second study outside North America were assigned to one of three treatment arms (saline injection, 55 IU or 75 IU Vitrase injection).
In both studies, patients with a vitreous hemorrhage for at least one month were enrolled if their hemorrhage was designated as severe and their best corrected-visual acuity was worse than 20/200 at the time of entry into the study. Treatment success for the primary (surrogate) endpoint in both studies was defined as the clearance of vitreous hemorrhage sufficient to allow the diagnosis and appropriate treatment, if needed, of the underlying cause of the vitreous hemorrhage within three months following treatment. Additionally, at each study visit and specifically at months one, two and three following treatment, BCVA was assessed using an eye chart.
Vitrase has received "fast-track" designation for the treatment of severe vitreous hemorrhage from the FDA. Fast-track designation, under the FDA Modernization Act of 1997, applies to those new drugs intended for the treatment of serious or life-threatening conditions that demonstrate the potential to address an unmet medical need. Currently, the only medical treatment for vitreous hemorrhage is surgery. Based on market research ISTA commissioned in 1999, we believe that approximately 450,000 cases of vitreous hemorrhage occur each year in the United States and that approximately half of these cases would be candidates for treatment using Vitrase.