In a dose-ranging phase IIb study, microplasmin 125 micrograms (ThromboGenics) was safe and demonstrated significant efficacy compared with placebo for inducing posterior vitreous detachment in eyes with macular holes or macular edema related to vitreomacular traction. Pivotal phase III trials are being planned.
Hong Kong-Results of a phase IIb study suggest that intravitreal injection of microplasmin (ThromboGenics) has promising potential to induce posterior vitreous detachment (PVD) safely and obviate the need for surgical intervention in some eyes with macular holes or macular edema related to vitreomacular traction, said George Williams, MD, at the World Ophthalmology Congress.
The phase IIb trial was a dose-ranging study with a randomized, placebo-controlled, double-masked design. It enrolled 125 patients at 19 centers across the United States. Eligible patients were scheduled for vitrectomy and had no evidence of PVD. They were randomly assigned to one of four groups to receive saline or microplasmin 25, 75, or 125 μg, 1 week prior to surgery.
The injections were well-tolerated, and no adverse events associated with microplasmin treatment were seen. The efficacy analyses demonstrated a dose-dependent effect, and the best response was found in patients treated with the 125-μg dose. Among the 32 patients in the highest-dose group, resolution of vitreomacular traction or closure of macular holes was achieved in 14 (44%), compared with one of 31 (3%) patients in the placebo group. Ten (31%) patients treated with microplasmin, 125 μg no longer needed vitrectomy, said Dr. Williams, chairman, Department of Ophthalmology, Beaumont Hospital, Royal Oak, MI.
"The role of the vitreous in retinal disease has long been recognized, especially in retinal detachment and vitreomacular traction involving macular holes and macular edema. More recently, there is evidence that vitreomacular traction may play a role in other diseases, including age-related macular degeneration [AMD]," Dr. Williams said. "While we believe that patients with macular holes and vitreomacular traction as demonstrated by [optical coherence tomography] have the best potential for avoiding surgery with this treatment, if we can confirm a therapeutic benefit in those populations, investigation of microplasmin will be expanded to other diagnoses, including patients with AMD and diabetic retinopathy with persistent macular traction."
In the phase IIb study, resolution of underlying disease to obviate need for vitrectomy also occurred in five of 33 patients treated with the 75 μg dose of microplasmin. Visual acuity also was assessed at day 35 post-treatment in all patients. In all microplasmin-treated patients, a mean improvement from baseline of 4.7 letters was seen. Patients in the highest microplasmin dose and placebo groups demonstrated a mean 6.9 letter and 0.1 letter improvement from baseline, respectively.
Microplasmin is one of several new pharmacologic modalities being investigated to manipulate the vitreous by inducing molecular changes to result in weakening of the vitreoretinal juncture and vitreous liquefaction.
"If those two events can be accomplished safely, we think there is a significant opportunity for using these drugs as a therapeutic intervention in many retinal diseases," Dr. Williams said.
He added that even patients who still required vitrectomy after microplasmin injection seemed to benefit from the treatment, probably because the enzyme weakens vitreoretinal adhesions to facilitate the surgery.
"In patients who progressed to surgical intervention, prior microplasmin treatment was associated with a reduced amount and duration of suction needed to achieve PVD compared with placebo," Dr. Williams said.
Although plasmin has been used therapeutically around the world for pharmacologic vitreolysis over the past decade, it has limitations because the molecule must be isolated from the patient's blood or obtained from pooled human plasma. Use of microplasmin, a recombinant DNA product, would avoid the difficulties of obtaining autologous plasmin and the potential risks of using allogeneic material, and it also would enable administration across a wide dose range, he said.