Ocriplasmin in exudative AMD: Safety and efficacy results

Take-Home

Ocriplasmin achieved complete resolution of vitreomacular adhesion (VMA) in more study patients with VMA and exudative age-related macular degeneration compared with patients in the sham group.

By Lynda Charters; Reviewed by Roger L. Novack, MD, PhD

Los Angeles-More patients treated with ocriplasmin (Jetrea, ThromboGenetics) achieved complete resolution of vitreomacular adhesion (VMA) compared with a sham group in a study that tested the safety and efficacy of the pharmacological treatment.

In addition, the drug was well tolerated, said Roger L. Novack, MD, PhD, in private practice with the Retina Vitreous Associates Medical Group, Los Angeles, and assistant clinical professor of ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles.

The MIVI-005 trial was a prospective, randomized, multicenter, sham-injected controlled study of the safety and efficacy of one injection of 125 µg of ocriplasmin in 100 patients with exudative age-related macular degeneration (AMD) and VMA. In the study, 75 patients were randomly assigned to receive the ocriplasmin injection and 25 patients to the sham injection.

Patients were evaluated with time-domain optical coherence tomography (OCT), spectral-domain OCT, fluorescein angiography, and color and fundus photography.

Treatment and sham injections were administered on day 1, and patients were evaluated on days 7 and 14. On day 28, the primary endpoint-i.e., resolution of focal VMA-was evaluated.

Patients were further evaluated at 3, 6, and 12 months after injection.

Secondary endpoints included the total posterior vitreous detachment (PVD) status, average macular thickness, best-corrected visual acuity (BCVA), and the number of anti-vascular endothelial growth factor (VEGF) injections required during the course of the study.

Average patient age was 74.5 years; 60% were women, and about 97% were Caucasian. Most were pseudophakic, and most had minimally classic and occult choroidal neovascularization.

MIVI-005 findings

Regarding the primary endpoint, 24.3% of treated patients achieved resolution of VMA on day 28 compared with 12% in the sham-treated group.

This difference did not reach significance (p = 0.262). The trial, however, was a proof-of-concept and safety study and was not sufficiently powered to show a significance difference in resolution of VMA between the two groups, Dr. Novack noted.

Regarding the secondary endpoints, 16.2% of treated patients achieved complete PVD on day 28 compared with 4% in the sham group (p = 0.175).

The mean best-corrected visual acuity levels in both groups were similar at each follow-up visit.

The mean number of anti-VEGF injections required by patients decreased by about 28% to 4.4 injections in the treated group compared with 6.1 injections administered in the sham group. The three primary anti-VEGF drugs used were ranibizumab (Lucentis, Genentech), bevacizumab (Avastin, Genentech), and aflibercept (Eylea, Regeneron Pharmaceuticals).

The mean central point retinal lesion thickness changed at each visit, but there was no difference between the treated and sham groups.

The National Eye Institute 25-item Visual Function Questionnaire-which measures parameters such as color vision, vision-related dependency, driving difficulty, and distance vision-did not show specific benefits associated with use of ocriplasmin.

Ocular adverse events

Among the most frequently reported ocular adverse events were visual acuity reductions, ocular pain, photopsia, and vitreous floaters-which was similar to the adverse events reported in the pivotal study of ocriplasmin, according to Dr. Novack.

About 40% of patients treated with ocriplasmin in both studies reported an adverse event, as did about 21% of patients in the sham groups.

In the MIVI-005 study, 3 patients who received ocriplasmin had a retinal detachment, 2 of which were not associated with the drug. Two patients had an episode of transient blindness associated with elevated IOP and resolved in about 1 hour.

Summarizing the findings

“A greater proportion of patients in the ocriplasmin group achieved the primary endpoint of resolution of VMA at day 28 after the injection compared to the sham group, said Dr. Novack, as he summarized the findings.

Ocriplasmin was generally well tolerated in patients with symptomatic VMA and vitreomacular traction and exudative AMD. No additional safety signals were identified in the current study compared with the pivotal study of ocriplasmin.

Data from this study do not show any additional clinically relevant benefit associated with the use of ocriplasmin in the treatment of symptomatic VMA/VMT in patients with exudative AMD. However, this population had been excluded from the phase III studies, he concluded.

Roger L. Novack, MD, PhD

E: rognov@laretina.com

Dr. Novack has no financial interest in any aspect of this report.