SUBSPECIALTY NEWS

Caution on Bilateral Same-day Avastin

Study finds laxity in preventing infections.

BY JERRY HELZNER, CONTRIBUTING EDITOR

■ A study by researchers at the UT Southwestern Medical Center in Dallas sounds a cautionary note for those ophthalmologists who give bilateral, same-day injections of compounded Avastin (bevacizumab, Genentech). The study, presented at the recent ARVO meeting, confirms that a significant number of doctors are not taking the safety steps designed to prevent infections such as endophthalmitis.

The frequency with which bilateral same-day intravitreal anti-VEGF injections (BSI) are performed is not well known. Moreover, special techniques for BSI to reduce risk of complications are not universally agreed upon or standardized. The researchers sought to determine current opinion among retina specialists of BSI, how frequently BSI are performed, and what measures are most frequently employed to prevent complications.

Initially, an online survey was distributed to retina specialists of the American Society of Retina Specialists and Dallas Academy of Ophthalmology via an online link. A total of 84 respondents completed the survey in early 2015.

Of the 82 physicians who reported performing frequent injections, 66 (80.4%) report performing BSI, with 53 (64.6%) performing at least monthly BSI. While a significant majority of respondents had cared for patients with unilateral endophthalmitis from intravitreal injection (69/82, 84.2%), a more significant majority had not cared for a patient with bilateral endophthalmitis (81/82, 98.8%). Of those who reported using bevacizumab, 66.2% (51/77) reported using a compounding pharmacy accredited by the Pharmacy Compounding Accreditation Board (PCAB).

Nearly half of the respondents (30/66, 45.5%) reported not taking any special measures with regards to lot, batch, or vial number because the issue had never been raised (19/66, 28.8%) or because of a lack of resources (11/66, 16.7%). A majority of respondents (54/82, 66%) felt that precautions related to lot and batch number were good but not necessary because the risk of bilateral complications is minimal.

The researchers concluded that BSI are performed frequently among retina specialists and by a higher percentage of retina specialists than previously documented through survey. Despite outbreaks linked to compounding of bevacizumab, there remains little consensus in practice about measures used to reduce the risk of bilateral complications, including whether precautions related to medicine lot, batch, or vial number are important.

Regorafenib Eyedrop Fails to Help AMD Patients

Bayer antiangiogenic was thought to have potential.

■ A group of international researchers led by Antonia M. Joussen, MD, of Berlin, Germany, set out to study the efficacy, safety, and tolerability of antiangiogenic regorafenib eyedrops (REG, Bayer) in treatment-naïve patients with wet AMD. REG is a multikinase inhibitor that acts mainly on the intracellular signaling of vascular endothelial growth factor receptors, which are known to play a primary role in the development and progression of wet AMD. REG has already been approved as an oral therapeutic for two types of cancer.

The DREAM study was a multicenter, single-arm, open-label, phase 2a/b study in which patients with choroidal neovascularization secondary to wet AMD received 1 drop (0.75 mg, 25 µL) of topical REG three times daily for 12 weeks in the study eye. The primary endpoint was the mean change in BCVA ETDRS letter score from baseline to weeks 4 and 12. Anatomic and safety outcomes were also measured at weeks 4 and 12.

A total of 51 wet AMD patients received treatment (mean age: 75 years; mean baseline BCVA: 59 letters; mean baseline central retinal thickness (CRT): 463.7 µm; mean CNV lesion size: 7.1 mm²; 84.3% had occult CNV and 15.7% had predominantly classic CNV.

The mean changes in BCVA were +1.2 letters and –2.4 letters at weeks 4 and 12, respectively. Patients with occult CNV lost fewer letters than those with classic CNV. The mean changes in CRT were +26 µm and +47 µm at weeks 4 and 12. Ocular treatment-emergent adverse events (TEAEs) were reported in the study eye of 21 patients (41.2%) by week 12; the majority were mild to moderate in severity (95.2%). There were one serious ocular TEAE (visual acuity reduced) and two serious nonocular TEAEs (ankle fracture and acute myocardial infarction resulting in one death), but none were drug related. A total of 21 patients required rescue medication (intravitreal ranibizumab).

DREAM was a phase 2a/b study investigating regorafenib eyedrops given three times daily for 12 weeks in patients with treatment-naïve wet AMD. The researchers, who presented their findings at the recent ARVO meeting, ended the study after completion of phase 2a because efficacy was not sufficient and did not approach historic levels seen with other wet AMD treatments. There were no drug-related safety concerns.

Clearside Meets Endpoints in RVO Trial

Combination therapy uses suprachoroidal space.

■ Clearside Biomedical (Alpharetta, GA) said its phase 2 clinical trial evaluating concomitant administration of suprachoroidal Zuprata, Clearside’s proprietary form of triamcinolone acetonide, together with intravitreal aflibercept (Eylea, Regeneron), for the treatment of macular edema associated with RVO, achieved its primary endpoint.

In preliminary results from the 46-patient trial, patients in the active arm (those receiving concomitant administration of Zuprata and Eylea) qualified for a statistically significant fewer intravitreal Eylea retreatments (9) than those patients in the control arm who initially received Eylea alone (23), during the three-month observation period following initial treatment. The trial, known as Tanzanite, is the first controlled, masked, randomized clinical trial conducted in patients with RVO where drug was administered through the suprachoroidal space.

Secondary endpoints in the trial included the mean change from baseline in BCVA and central subfield thickness. For the BCVA endpoint, at month 1, patients in the active arm had an average improvement of approximately 16 letters, or more than three lines on a standard eye chart, compared to approximately 11 letters of improvement, or just over two lines, for patients in the control arm, each from their respective baseline measurements. At the end of the three-month observation period, patients in the active arm had an average improvement of approximately 19 letters, while patients in the control arm maintained their same level of improvement at approximately 11 letters.

In the secondary objective of measuring the central subfield thickness, at month 1, patients in both arms showed a mean reduction of more than 400 µm. Patients in the active arm maintained this level of reduction throughout the three-month trial, while patients in the control arm had smaller levels of reduction as the trial progressed, with the mean reduction declining to approximately 340 µm for patients in the control arm beginning in month 2. In terms of safety results, there were no serious adverse events reported in the trial, and the treatment was generally well tolerated. Clearside plans on submitting the full data set for presentation at an upcoming medical meeting.

“The preliminary data from this clinical trial continue to provide support for the treatment of certain blinding eye diseases through suprachoroidal space administration of Zuprata and the potential for an effective and safe option for the treatment of RVO,” said Daniel H. White, CEO and president of Clearside. “Based on these results, Clearside intends to follow a 505(b)(2) NDA regulatory approval pathway and expedite the preparations for a Zuprata phase 3 registration program for the treatment of macular edema associated with RVO.”

Switching Anti-VEGF Drugs Can Improve Vision

ROTATE trial produces seven-letter BCVA gains.

■ Researchers from the Southeast Retina Center (Evans, GA) wanted to determine if switching patients with persistent DME from Avastin (bevacizumab, Genentech) to 0.3 mg Lucentis (ranibizumab, Genentech) could improve both BCVA and central subfield thickness (CST).

To test their hypothesis, they initiated the ROTATE trial, an open-label, prospective, unmasked, randomized study of intravitreally administered 0.3 mg ranibizumab in 30 eyes with persistent DME after bevacizumab. Thirty eyes were randomized in a 1:2 ratio to a Sustained group (12 mandatory monthly injections of 0.3 mg ranibizumab through 1 year) or a PRN group (six mandatory monthly injections of 0.3 mg ranibizumab, followed by criteria-based PRN dosing). Subjects were evaluated monthly for additional ranibizumab or rescue treatment.

Twenty-nine of 30 enrolled eyes completed 12-month follow-up. At baseline, mean BCVA was 63 (Snellen equivalent 20/63) and 64 (Snellen equivalent 20/50) ETDRS letters, in the Sustained and PRN groups, respectively. Mean baseline CST was 401 µm and 453 µm in the Sustained and PRN groups, respectively. At 12 months, mean BCVA was 70 (Snellen equivalent 20/40) and 71 (Snellen equivalent 20/40) letters in the sustained and PRN groups, respectively. Average visual acuity increased 6.7 and 7.1 letters at 12 months from baseline in the Sustained and PRN groups respectively, with 16 of 30 eyes gaining ≥ 5 letters at 6 months. At 12 months, mean CST was 307 µm and 331 µm in the Sustained and PRN groups, respectively. Average OCT central subfield thickness thinned 92 µm and 129 µm at 12 months from baseline in the Sustained and PRN groups, respectively; 22 of 29 eyes decreasing thickness by at least 10% through 6 months.

The researchers, who presented their findings at the recent ARVO meeting, concluded that ranibizumab 0.3 mg may provide additional visual acuity and anatomic benefit for eyes with persistent DME after recent, chronic, and frequent bevacizumab. RP