In an unexpected outcome, Dr. Pravin Dugel presented the 2-year results of the CABERNET study, evaluating the use of NeoVista’s VIDION ANV epimacular brachytherapy device at the Bascom Palmer Eye Institute's (BPEI) Angiogenesis, Exudation, and Degeneration 2012 Meeting in Miami on Februay 4th.
As described in the following extensive writeup from Retina Today, the Phase 3, multicenter, prospective, randomized study did not achieve its primary endpoint after two years.
As I have previously written (see Update 4), the device has been commercialized extensively in Europe and the company was hoping that promising results in the CABERNET study would lead to FDA approval for marketing in the U.S. Those plans may now be on hold until subset analysis is completed and/if a subset of patients can be identified that would benefit from use of the device.
I asked NeoVista if they wished to comment about this development, and the company said that they would have no comment at this time.
Retina Today eNews, 2/13/12
Based on visual acuity outcomes, the CABERNET study evaluating epimacular brachytherapy for the treatment of wet age-related macular degeneration (AMD) did not achieve its primary endpoint at 2 years, according to Pravin U. Dugel, MD. Dr. Dugel presented the 2-year results of the CABERNET study at the Bascom Palmer Eye Institute's (BPEI) Angiogenesis, Exudation, and Degeneration 2012 meeting in Miami.
The phase 3, multicenter, prospective, randomized CABERNET study included 457 treatment-naïve patients who were divided into 2 arms. Patients in the treatment arm (n=302) underwent strontium-90 beta radiation with epimacular brachytherapy (NeoVista) and 2 mandatory ranibizumab (Lucentis, Genentech) injections. Patients in the control arm (n=155) received ranibizumab injections following a modified PIER protocol, which included 3 initial monthly injections followed by injections once every 3 months. In the CABERNET study, patients were seen on a monthly basis, and rescue therapy was permitted, as per the investigators' discretion.
The primary endpoint of CABERNET was visual acuity, specifically, the percentage of patients losing fewer than 15 letters of vision. In patients treated with epimacular brachytherapy, 6 injections were required at the 2-year mark for a mean 2.5 letter loss. Patients treated with ranibizumab required 11 injections and achieved a mean 4.4 letter gain.
In a post-study, unplanned subgroup analysis, the investigators identified 44% of patients in the epimacular brachytherapy group who required no rescue injections through the first 12 months and 1 rescue injection through the second 12 months, with a mean 3.3 letter gain, Dr. Dugel said.
In a similar analysis, the investigators identified 25% of patients in the epimacular brachytherapy arm who required no rescue injections throughout the 2-year course of the study, with a mean gain of 5.7 letters.
Cataract formation occurred in 48% of patients in the epimacular brachytherapy arm, which was suspected to be due to vitrectomy procedures, according to Dr. Dugel. The difference in the APTC events between the 2 study groups was not clinically significant.
At the 2-year mark, there were 10 patients with suspected radiation-based retinopathy. "There are 2 important things about these patients," Dr. Dugel said. "The first being that these 10 patients had changes that were nonproliferative and nonprogressive throughout the 2-year course of the study; the second, as a group, these patients tended to do fairly well. The mean change in visual acuity was +4.4 letters of vision. None of these patients lost significant vision, and the mean number of injections was 4."
The CABERNET demonstrated an acceptable safety profile for epimacular brachytherapy at the 2-year mark and identified a subgroup of patients that tended to respond well to the treatment. However, the CABERNET study did not achieve its primary endpoint, and it is not yet known whether the subgroup of patients who benefitted from the device can be reliably and consistently identified in clinics, Dr. Dugel concluded.
"At the end of the day, I think it is important to keep this study in proper perspective," Dr. Dugel said. "It was started in 2006 when there were few treatment alternatives. In retrospect, the CABERNET study should not have included treatment-naïve patients, but rather, should have treated previously ranibizumab-treated patients only. The CABERNET study should have [also] placed a lot more importance on probe placement."
Editor’s Note: It should be noted that Dr. Dugel is a consultant to and minority shareholder of NeoVista.