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Intravitreal faricimab (previously known as RG7716, Genentech/Roche) shows promise for improving outcomes and reducing the treatment burden for diabetic macular edema (DME), according to results of a phase II study.
Faricimab is a first-in-kind bispecific antibody that simultaneously binds and neutralizes VEGF-A and angiopoietin-2, said Arshad M. Khanani, MD, MA, BOULEVARD Investigator, managing partner and director of clinical research at Sierra Eye Associates and clinical associate professor, University of Nevada, Reno, NV. The agent is also optimized for fast systemic clearance and to avoid effector function.
Known as BOULEVARD, the phase II study compared faricimab at doses of 1.5 mg and 6.0 mg against ranibizumab 0.3 mg (Lucentis, Genentech).
Patients received six monthly injections (up to week 20), after which they were followed monthly (off treatment), up to week 36 to evaluate the durability potential of the drug. The primary endpoint analyzed adjusted mean change in BCVA letter score from baseline to week 24 in treatment-naÃ¯ve patients, which showed a statistically significant difference favoring faricimab 6.0 mg against ranibizumab (13.9 vs. 10.3 letters; P=.03).
Analyses looking at percentages of patients achieving ≥2-line or ≥3-line improvements in BCVA and improvements in Diabetic Retinopathy Severity Score (DRSS) (DRSS simplified conversion table (http://www.icoph.org/dynamic/attachments/resources/diabetic-retinopathy-detail.pdf)) also favored faricimab over ranibizumab. In addition, the investigational agent showed a benefit for better control of disease activity during the 16-week observation period, following the last study injection, Dr. Khanani said.
“Angiopoietin-2 levels are elevated in the vitreous of patients with diabetic retinopathy (DR) and DME. The results from this phase II study confirm the role of blocking angiopoietin-2 to stabilize the vasculature and decrease leakage and inflammation in these patients,” Dr. Khanani said. “Two large global phase III pivotal studies, YOSEMITE and RHINE, have been initiated and are currently enrolling patients (clinicaltrials.gov id: NCT03622580).”
BOULEVARD is a U.S. multicenter, randomized, double-masked study that enrolled 229 patients (168 treatment-naÃ¯ve and 61 previously treated) with diabetic macular edema and decreased visual acuity (20/320 to 20/40).
Highlighting some results from secondary outcome measures in the treatment-naÃ¯ve patients, Dr. Khanani reported that a ≥2-line gain in BCVA from baseline to week 24 was achieved by 57.0% of patients in the ranibizumab group, 61.2% of patients treated with faricimab 1.5 mg, and 70.5% of those receiving faricimab 6.0 mg. Rates of patients with a ≥3-line improvement in BCVA in the three treatment groups were 32.7%, 36.7%, and 43.2%, respectively.
“These data show that compared with ranibizumab, faricimab 6.0 mg was associated with impressive relative increases of 24% in the percentage of 2-line gainers and 32% in the percentage of 3-line gainers in treatment-naÃ¯ve patients,” Dr. Khanani said.
Data on central subfield thickness changes from baseline to week 24 supported the primary efficacy outcome, showing a dose-dependent effect with faricimab and more improvement with the investigational agent compared with ranibizumab.
Effect on diabetic retinopathy
In the treatment-naÃ¯ve study population, 39% of patients treated with faricimab 6.0 mg and 12% of ranibizumab-treated patients had a ≥2-step improvement in DRSS at week 24. Among the high-risk population with a baseline DRSS ≥53 (i.e., ≥ severe nonproliferative diabetic retinopathy), 25% of ranibizumab-treated patients versus 88% of those treated with faricimab 6.0 mg showed an improvement of at least 2 steps in their diabetic retinopathy severity.
In the off-treatment observation period, patients treated with faricimab 6.0 mg showed potential for extended durability with a higher proportion of patients maintaining disease stability over time after the last dose.
Faricimab was well-tolerated and showed no new or unexpected safety signals.
This article is based on a presentation given by Dr. Khanani at the 2018 World Ophthalmology Congress in Barcelona, Spain. Dr. Khanani is a consultant for Genentech and Roche.