Clinical Trials

Date: 2012-08-15

Type of information: Publication of results in a medical journal

phase: 3

Announcement: publication of results in The New English Journal of Medicine

Company: Thrombogenics (Belgium)

Product: Jetrea® (ocriplasmin)

Action mechanism:

• protein. Ocriplasmin, a recombinant, truncated form of human protein (plasmin), works by dissolving the proteins that link the vitreous to the macula (center of the retina), relieving the traction and resulting in posterior detachment of the vitreous from the retina.

Disease: symptomatic vitreomacular adhesion or vitreomacular traction (VMT)

Therapeutic area: Ophtalmological diseases

Country: USA, Europe

Trial details:

• Study 006 and Study 007 are two multicenter, randomized, double-blind, placebo-controlled Phase III studies to test the efficacy and safety of a single intravitreal injection of ocriplasmin in patients with vitreomacular traction and macular holes. One half and one third of the patients enrolled in Study 006 and Study 007, respectively, received placebo; all other patients received a single intravitreal injection of ocriplasmin (125 microgram). The primary endpoint for the studies was the percentage of eyes with nonsurgical resolution of vitreomacular adhesion at day 28, determined by optical coherence tomography (OCT) imaging. After 28 days, following a single administration of ocriplasmin, resolution of vitreomacular adhesion was observed in 26.5% of patients compared to 10.1% in the placebo group, (p<0.001). This statistically significant difference was maintained through six months of observation. For those patients with resolution of vitreomacular adhesion after ocriplasmin administration, resolution was achieved in the majority of patients within seven days. By the end of the six months observation period, fewer patients required a vitrectomy in the ocriplasmin treated group, compared to placebo (17.7% vs. 26.6% respectively, p=0.02). In the ocriplasmin group, ocular adverse events occurring in the studied eye were transient and mild in severity, the most common adverse event being self-reported vitreous floaters (in 68.4% of patients compared to 53.5% in the placebo group). In the group treated with ocriplasmin, the incidence of any serious ocular adverse event was 7.7%, compared to 10.7% in the placebo group, (p=0.26).

Latest news:

• • On August 15, 2012, ThromboGenics has announced that the data from two Phase III clinical trials evaluating ocriplasmin for the treatment of vitreomacular traction (VMT) and macular holes will be published in the New England Journal of Medicine on 16 August 2012. The paper highlights that a single intravitreal injection of ocriplasmin resolved Vitreomacular Adhesion (VMA), releasing traction and closing macular holes in significantly more patients than placebo. The two multicenter, randomized, double-blind Phase III trials met the primary endpoint of pharmacological resolution of VMA at day 28. Secondary endpoints included nonsurgical closure of a macular hole at 28 days, avoidance of vitrectomy (surgery) and improvement in visual acuity. The Phase III program found that 26.5% of patients treated with ocriplasmin saw resolution of VMA, compared with 10.1% of patients receiving placebo (p<0.001). Nonsurgical closure of macular holes occurred in 40.6% of ocriplasmin-treated patients, compared with 10.6% of patients on placebo (p<0.001). Patients given ocriplasmin were more likely to achieve a vision gain of at least three lines compared with placebo. Treatment with ocriplasmin was associated with some, mainly transient ocular adverse events. Dr Julia Haller, Ophthalmologist-in-Chief of the Wills Eye Institute, and Professor and Chair of the Department of Ophthalmology at Thomas Jefferson University, said: “This New England Journal of Medicine paper highlights data showing ocriplasmin’s potential to become the first pharmacological option for the treatment of symptomatic VMA and macular holes. An in-office injection would be a new and possibly earlier alternative treatment for the vitreoretinal surgeon to offer to patients with these sight threatening disorders. Ocriplasmin represents a potential new treatment paradigm for the retina community and for our patients with VMA and macular holes.” ThromboGenics has made regulatory filings for ocriplasmin in both the U.S. and Europe. In July, an FDA advisory panel recommended the approval of ocriplasmin for the treatment of symptomatic VMA. If approved, the Company plans to commercialize ocriplasmin itself in the U.S . In Europe ocriplasmin is currently under regulatory review by the European Medicines Agency (EMA). In March 2012, ThromboGenics signed a strategic partnership with Alcon for the commercialization of ocriplasmin outside the United States. • On August 22, 2011, ThromboGenics announced that new data, including six month outcomes, from its pivotal ocriplasmin Phase III clinical program were presented at the 2011 ASRS Annual Meeting in Boston, USA (20-24 August 2011).  In 2010, ocriplasmin successfully completed two pivotal Phase III trials (TG-MV-006 and TG-MV-007) involving a total of 652 patients in Europe and the U.S. Both Phase III trials met the primary endpoint of non-surgical resolution of focal vitreomacular adhesion one month after a single injection of ocriplasmin. Dr Dugel presented “Ocriplasmin for the Treatment of Vitreomacular Traction Syndrome: Phase III Results.” Key highlights included: • New data confirming earlier Phase III results that a single injection of ocriplasmin resolved VMA and the visual symptoms associated with it in 29.8% of VMT patients, compared with 7.7% of patients on placebo (28 days), a highly statistically significant result (p=0.001). • 10.1% of patients in the ocriplasmin arm gained three lines in visual acuity compared with 5.1% on placebo (6 month follow up). • Ocriplasmin was associated with a lower incidence of retinal tears or detachments, seen in just 1.7% of patients, compared with 4.3% on placebo (6 months). Dr Kaiser presented six-month follow-up data on “Ocriplasmin for the Treatment of Macular Hole: Phase III Results.” The main points included: • Approximately 40.6% of patients with full thickness macular hole (FTMH) achieved closure compared with 17% on placebo (p=0.004). • Approximately 58% of patients with FTMHs smaller than 250 ?m saw closure with ocriplasmin compared with just 20% in placebo patients. • 27% of patients gained ? 3 lines in visual acuity after six months of treatment with ocriplasmin, compared with 13% on placebo.

Is general: Yes