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A single intravitreal injection of ocriplasmin is safe, effective, well-tolerated, and is the first pharmacologic treatment for symptomatic vitreomacular adhesion.
Ninety investigators in the United States and Europe participated in the two prospective, double-masked Microplasmin for IntraVitreous Injection-Traction Release withoUt Surgical Treatment (MIVI-TRUST) studies that enrolled adult patients with vitreomacular traction (VMT) or full-thickness macular hole (FTHM) <400 µm that, in the opinion of the investigator, was related to decreased visual function. The protocol excluded individuals with proliferative retinopathy, exudative age-related macular degeneration (AMD), retinal vein occlusion, high myopia, aphakia, vitreous hemorrhage, or vitreous opacification in the study eye.
Participants were randomly assigned to receive intravitreal injection of 100 µl placebo solution (188 patients) or 125 µg ocriplasmin (464 patients). The proportion of patients that achieved resolution of sVMA at day 28 as determined by masked optical coherence tomography evaluation at a Central Reading Center was analyzed as the primary efficacy endpoint. The data showed a highly statistically significant difference favoring ocriplasmin over the control group (26.5% versus 10.1%; p < 0.001), and an even higher response rate was achieved in the subgroup of ocriplasmin-treated patients without an epiretinal membrane.
Significant on many levels
"The results of these well-designed, prospective studies show that ocriplasmin had benefits that were not only statistically significant, but also clinically significant, and that it had a favorable safety profile as well," said Steven D. Schwartz, MD, MIVI-TRUST investigator and associate professor and chief of the retina division, Jules Stein Eye Institute, University of California Los Angeles. "Therefore, the clinical portion of the ocriplasmin biologic license application for an indication in the treatment of sVMA should be very strong.
"If the favorable safety profile of ocriplasmin holds up with further scrutiny, its activity is very exciting considering its potential role in a broad range of indications, including in the management of diabetic retinopathy and AMD where presence of VMA worsens the prognosis," he said. "This drug might allow intervention in patients with earlier-stage VMA who might otherwise be assigned to watchful waiting because the risk:benefit ratio does not justify invasive surgery, offer an alternative to patients who are surgical candidates, and/or become an adjunct to surgery."
Results from the secondary efficacy analyses showed closure of FTMH was achieved in 40.6% of ocriplasmin-treated eyes at 28 days (p < 0.001 versus placebo) and maintained at 6 months; total posterior vitreous detachment was induced in 13.4% of eyes with ocriplasmin injected (p < 0.001 versus placebo). All visual acuity and visual function outcomes (VFQ-25) favored ocriplasmin.
"As an investigator in the phase II and III studies, I was masked to treatment," Dr. Schwartz said. "However, it was clear during follow-up that a number of patients benefited clinically in a profound way. Based on my experience in the premarketing clinical trials, I look forward to being able to offer patients with sVMA the option of receiving intravitreal ocriplasmin and the potential to avoid surgery."
The safety data from the MIVI-TRUST trials showed intravitreal ocriplasmin was well-tolerated. Most ocular adverse events occurred at similar rates in the two groups.
Steven D. Schwartz, MD
Dr. Schwartz was an investigator in the phase II and III studies of ocriplasmin for treatment of symptomatic vitremomacular adhesion. He currently is conducting a study at UCLA investigating whether intravitreal injection of ocriplasmin to relieve vitreomacular adhesion in eyes with exudative age-related macular degeneration might improve the response and or provide a durable response to intravitreal anti-vascular endothelial growth factor therapy. He has no other financial interest.