22.
Microplasmin: Update on Clinical Development
for Treatment of Vitreoretinal Disorders
Steve Pakola (New York)
Microplasmin is a recombinant, truncated form of plasmin with retained protease activity.
Given that microplasmin cleaves both laminin and fibronectin, it is considered an ideal candidate
for pharmacologic vitreolysis. After completion of pharmacology experiments demonstrating
the expected ability to induce posterior vitreous detachment (PVD), an initial clinical trial
evaluating microplasmin intravitreal injection in 60 patients undergoing vitrectomy was completed
(the MIVI I trial). Final results demonstrated that the drug was generally well tolerated,
with numerous cases of spontaneous PVD reported.
Based on these results, three additional trials were initiated and are currently ongoing:
MIVI II DME trial – 60 pt trial in patients with DME (Europe)
MIVI II Traction trial – 60 pt trial in patients with vitreomacular traction (Europe)
MIVI III trial – 120 pt trial in patients scheduled for vitrectomy (U.S.)
To date approximately 200 patients have received microplasmin via intravitreal injection. Study drug has been generally well
tolerated. Additionally, as presented at the American Society of Retina Specialists (ASRS) annual meeting on December 4,
2007, microplasmin has shown evidence of benefit in numerous patients. Specifically, in the MIVI II Traction trial, 9 of 24
microplasmin treated patients (75 to 125 μg) achieved resolution of their vitreomacular traction (including macular hole closure
in 2 of the 4 macular hole cases) without the need for vitrectomy. In contrast, none of the 6 sham injected patients had
resolution of their vitreomacular traction (including two patients with macular hole). Current status of the ongoing trials and
future directions for microplasmin clinical development will be discussed.