Vitrase trials show reduction in vitreous hemorrhage density

IRVINE, Calif. — Intravitreous injection of a hyaluronidase product demonstrated a significant reduction in vitreous hemorrhage density in data pooled from two phase 3 trials, according to recent publications.

Ista Pharmaceuticals announced this week that the results of two phase 3 trials evaluating its product Vitrase (ovine hyaluronidase) for the treatment of vitreous hemorrhage have been published in the American Journal of Ophthalmology.

Vitrase was approved by the Food and Drug Administration as a spreading agent for ocular anesthesia in 2004. It was reviewed by an FDA advisory panel in 2003 for the indication of vitreous hemorrhage clearing but was not recommended for approval of that indication.

According to Ista, in the pooled data from the two phase 3 trials, the drug demonstrated a statistically significant reduction in vitreous hemorrhage at 1 month after a single intravitreous injection, compared to a single injection of saline.

The reduction in hemorrhage density allowed investigators to see into the posterior segment to diagnose the underlying cause of the hemorrhage and to treat with laser when appropriate, according to a press release from the company.

Two randomized, double-masked, placebo-controlled international studies were conducted, enrolling a total of 1,306 patients. A North American study involved 750 patients who received either saline injection or 7.5 IU, 55 IU or 75 IU of Vitrase. A study outside North America included 556 patients who received either saline injection or 55 IU or 75 IU of Vitrase, according to the press release.

Patients in the study all had severe vitreous hemorrhage with a visual acuity worse than 20/200 at the time of enrollment.

“The study results suggest a therapeutic utility of ovine hyaluronidase in the management of vitreous hemorrhage,” said Lisa R. Grillone, PhD, vice president of clinical research and medical affairs at Ista, in the release. “This may allow for earlier treatment of the underlying pathology while minimizing the risk to the patient.”

Dr. Grillone was one of the authors of two papers published in AJO describing the safety and efficacy results from the pooled study data.

“The goal of treatment with an intravitreous injection of ovine hyaluronidase is to provide a safe treatment alternative to reduce and/or clear vitreous hemorrhage density sufficiently to provide earlier visualization of the retina,” Dr. Grillone said. “This would facilitate the physician’s ability to diagnose the underlying retinal pathology and assess the need for additional treatment, as well as restore the subject’s visual acuity when there is adequate retinal function.”

The two phase 3 trials demonstrated that patients receiving a single Vitrase injection showed improved best corrected visual acuity by three or more lines from 1 month through 3 months after injection, compared to those who received saline injection, according to the release.

“No serious safety issues” were observed following a single injection of Vitrase in the trials, according to the press release. The most common adverse effect during the trials was acute iritis, the release said.

“Other statistically significant ocular adverse events observed in the two trials, one of which was conducted outside North America, were hyperemia and ocular pain,” the release stated. “Additional statistically significant ocular adverse events in the North American study included eye irritation, increased lacrimation, reduced visual acuity, vitreous hemorrhage, photophobia and photopsia.”