July 27, 2012 — An advisory committee to the US Food and Drug Administration (FDA) voted July 26 to recommend ocriplasmin (Jetrea, ThromboGenics, Inc) 125 μg intravitreal injection for the treatment of symptomatic vitreomacular adhesions (sVMAs), including macular hole.
The committee voted unanimously to recommend approval of ocriplasmin for the treatment of VMAs, and 7 to 3 in favor of recommending approval for treatment of macular holes. "I thought the anatomic data was very favorable," Stephen S. Feman, MD, MPH, a professor at Saint Louis University School of Medicine in Missouri and voting committee member, said during the advisory meeting.
Symptomatic VMAs result from incomplete separation of the vitreous from the macula and can be progressive and result in blindness. At this time, the only treatment option is vitrectomy, a major surgical procedure that is usually postponed until late in the disorder because of the potential risks and difficult recovery period. Ocriplasmin is the first pharmacologic treatment for symptomatic VMAs and could improve outcomes by making treatment available earlier.
Ocriplasmin is a recombinant truncated form of the human serine protease plasmin with retained enzymatic activity that acts on collagen, fibronectin, and laminin to liquefy the vitreous, resulting in its detachment from the macula.
The committee discussed data from 2 randomized, phase 3, placebo-controlled studies, TG-MV-006 and TG-MV-007. Each study had 326 participants, and a total of 652 eyes were injected.
The studies enrolled patients with sVMA, which was described as vitreomacular traction with or without a full-thickness macular hole.
Patients were seen for 7 visits during a 6-month period: at baseline and on injection day (day 0), postinjection day 7, postinjection day 14, postinjection day 28, postinjection month 3, and postinjection month 6.
Efficacy
The primary efficacy endpoint was the proportion of patients whose focal VMA resolved without surgery at day 28 postinjection, as determined by masked central reading center optical coherence tomography evaluation.
The secondary efficacy endpoint was the proportion of patients who had total posterior vitreous detachment at day 28, as determined by masked investigator assessment of B-scan ultrasound.
Primary endpoints were achieved in each study, and statistically significantly higher VMA resolution rates were seen at day 28 in patients who received a single injection of 125 μg ocriplasmin compared with placebo.
In study TG-MV-006, 13.1% (n = 107) of patients who received placebo and 27.9% (n = 219) of patients who received ocriplasmin met primary efficacy endpoints.
In study TG-MV-007, 6.2% (n = 81) of patients who received placebo and 25.3% (n = 245) of patients who received ocriplasmin met primary efficacy endpoints.
Safety
Data from a total of 7 completed studies, including TG-MV-006 and TG-MV-007, also were analyzed for safetyas well. Of note, 9 of 976 ocriplasmin-treated patients experienced temporary, postinjection serious and/or severe adverse events that involved acute vision decrease within 24 hours of injection. Vision returned to at least pretreatment levels (median time, 2 weeks) in all but 1 patient, whose vision decrease was considered to be related to concurrent retinal disease. The reasons for this are unclear.
A total of 8 patients from the 7 studies died; 6 were in the treatment group and 2 were in the placebo group. None of the deaths were related to treatment.
"The majority of patients who receive this drug will not get benefit from the drug, and I think that that needs to be very clearly stated. If the drug is approved, it must be very clearly stated in labeling.... Even though there is efficacy benefit over risk...the majority of patients will not see a benefit from this drug," said Lynn Gordon, MD, PhD, a professor of ophthalmology at Jules Stein Eye Institute and associate dean of diversity affairs at David Geffen School of Medicine at the University of California, Los Angeles, and voting committee member, said during the advisory meeting.
"I agree with [Dr. Gordon's] concerns, but I suspect that the sponsor will look at, and the ophthalmology community will identify, which patients have a higher potential for benefit with this treatment," said Susan MacDonald, MD, director of comprehensive ophthalmology and assistant professor at Tufts University School of Medicine, Boston, Massachusetts, also a voting committee member, said during the advisory meeting.
"I believe that if you can reduce the number of people that need vitrectomy by 25% by using this medication, you're really making a benefit to mankind," said Dr. Feman.
No relevant financial relationships were disclosed by the voting committee members. The industry representative is employed by Forest Laboratories.
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