The biosimilar FYB201 may offer patients with neovascular age-related macular degeneration (nAMD) a safe, effective and cheaper alternative to ranibizumab, an industry-funded study suggests. "The manufacturer demonstrated that FYB201 has an efficacy and side-effect profile comparable to ranibizumab during the first 48-week period of treatment," said Dr. Tongalp H. Tezel, a professor of ophthalmology at Columbia University Vagelos College of Physicians and Surgeons, in New York City, who was not involved in the research. "This study was mandated by the Food and Drug Administration (FDA) as a part of the approval process as stated in the Biologics Price Competition and Innovation Act (BPCIA) and FDA's Biosimilars Action Plan," Dr. Tezel explained in an email to Reuters Health. Lead author Dr. Frank G. Holz of the University of Bonn in Germany and colleagues conducted the phase-3 COLUMBUS-AMD randomized controlled trial in patients 50 years of age and above with treatment-naive, subfoveal choroidal neovascularization due to nAMD at sites in twelve countries. Every four weeks over 48 weeks, 238 patients received a 0.5-mg intravitreal injection of FYB201, and 239 patients received the same dose of ranibizumab, in the study eye. As reported in Ophthalmology, the researchers measured change from baseline in best corrected visual acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at eight weeks, before participants received their third injection. Biosimilarity of FYB201 and ranibizumab was determined by a two-sided equivalence test, with an equivalence margin in BCVA of three ETDRS letters. BCVA improved in both groups and the primary endpoint was met at week 8, with a mean of +5.1 ETDRS letters in the FYB201 group and +5.6 in the ranibizumab group. The analysis of covariance (ANCOVA) least-squares mean difference for the change from baseline between FYB201 and ranibizumab was -0.4 ETDRS letters, a non-significant difference. In both groups, 8.4% of patients developed treatment-emergent intraocular inflammation from all causes; and in both groups, 0.8% of patients developed treatment-emergent intraocular inflammation, including iridocyclitis and conjunctivitis in those receiving FYB201 and punctate keratitis in those on ranibizumab. In both groups, 5.9% of patients developed antidrug antibodies, and the groups had similar antidrug antibody titers. Between weeks 24 and 48, one participant receiving FYB201 developed neutralizing antibodies. "I hope this study will allow the path for many more biologicals to enter the US market and reduce the cost of current anti-VEGF (vascular endothelial growth factor) treatment," Dr. Tezel said. "The main limitation originates from the undisclosed details," he cautioned. "The authors claim that FYB201 has comparable properties, strength, posology, and storage characteristics, but no data were supplied. Thus, physicians reading this report have no idea about the pharmacodynamics or pharmacokinetics of this drug inside the eye." "Without additional knowledge such as molecular weight, binding affinity, etc.," he added, "it is difficult to have a complete picture about the value of FYB201 against ranibizumab." Dr. Shree Kurup, a professor of ophthalmology at Case Western Reserve University in Cleveland, Ohio, called the study "the first rigorous evaluation of a biosimilar in ophthalmology and a demonstration of healthcare-cost control." "We have very effective drugs for neovascular AMD, but they are expensive," he told Reuters Healthy by email. "Biosimilar drugs such as FYB201 may replace expensive drugs." Dr. Kurup, who also was not involved in the study, noted, "When you design antibodies for therapeutic use, one major limitation is the propensity to induce inflammation, which can be devastating in the eye . . . Post-marketing surveillance would be essential to see what happens as the new drug is used. Quite often, that's when side effects become more apparent." The findings were also presented November 13 at AAO 2020, the American Academy of Ophthalmology (AAO)'s virtual annual meeting. The COLUMBUS-AMD trial was sponsored by the Swiss biopharmaceutical company bioeq GmbH. Five of six authors report financial relationships with the company, and one author is an employee. Drs. Tezel and Kurup have no ties to bioeq. Dr. Holz did not respond to requests for comments. —Lorraine L. Janeczko Source
