Phase 3 Study Demonstrates Comparable Safety, Efficacy Between Ranibizumab Biosimilar, Lucentis for nAMD

Proposed biosimilar FYB201 is considered biosimilar to reference ranibizumab (Lucentis) in terms of clinical efficacy and safety in the treatment of patients with newly diagnosed subfoveal neovascular age-related macular degeneration (nAMD), and may be a new patient treatment option, according to a study published in Ophthalmology.

This trial, called the COLUMBUS-AMD trial, was conducted to study the clinical equivalence of FYB201 and reference ranibizumab in patients with nAMD. It was an evaluation-masked, parallel-group, multicenter, 48-week, randomized phase 3 study to assess the clinical equivalence of FYB201 (Formycon/bioeq) with reference ranibizumab (Roche/Genentech) in clinical pharmacology, efficacy, and safety for the treatment of patients with treatment-naïve, subfoveal choroidal neovascularization caused by nAMD.

So, the primary endpoint consisted of change from baseline in best-corrected visual acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 8 weeks prior to the third monthly intravitreal (IVT) injection. Biosimilarity of FYB201 to its originator was measured via a 2-sided equivalence test, with an equivalence margin in BCVA of 3 ETDRS letters.

It is known that AMD causes 8.7% of global blindness and is the most common cause of blindness in older people from high-income countries. nAMD is sometimes considered advanced AMD, and makes up 10% to 15% of all AMD cases, with more than 90% of AMD-related severe visual loss attributed to nAMD.

“Anti-[vascular endothelial growth factor] treatment for nAMD management carries a substantial burden for patients and healthcare systems, especially the cost of the medication. Treatment burden due to frequent and expensive injections may limit outcomes in clinical practice and affects and causes additional burden on insurance companies and their reimbursement policies.”

Reference product ranibizumab is an effective nAMD treatment that has a short half-life that minimizes systemic effects. To date, biosimilar use in ophthalmology has been limited. Currently, there are 2 approved ranibizumab biosimilars in the United States and 3 in the European Union, including FYB201, which is marketed as Cimerli in the United States and Ranivisio in Europe. FYB201 is also approved in the United Kingdom as Ongavia. Cimerli is also the only ophthalmology biosimilar to have an interchangeability designation. The use of ophthalmology biosimilars is still a new development.

In the study, a total of 477 patients were randomly assigned to receive either FYB201 (n = 238) or reference ranibizumab (n = 239), both in 0.5 mg by IVT injection in the study eye every 4 weeks. During the study, 199 patients in the FYB201 group and 189 patients in the reference ranibizumab group received the full 12 injections, and the number of missed injections was well balanced across treatment groups.

The patients came from sites in Austria, Czech Republic, France, Germany, Hungary, Israel, Italy, Poland, Russia, Spain, Ukraine, and the United Kingdom. This study presents findings relevant to the US population.

Ultimately, both groups saw BCVA improvement, with a mean improvement of +5.1 ETDRS letters in the biosimilar group and +5.6 letters in the reference product group at week 8. The analysis of covariance least squares mean difference for the change from baseline between FYB201 and reference ranibizumab was –0.4 ETDRS letters with a 90% CI of –1.6 to 0.9. Since the 90% CI was within the predefined equivalence margin, the primary end point was met.

In the US-relevant population, the mean BCVA improved in both groups, with a mean change of +5.1 letters in the biosimilar group and +5.6 letters in the reference ranibizumab group at week 8. The 95% CI for the difference was contained within the prespecified equivalence margin, and the primary end point was met. The same trends and effect similarity was seen between FYB201 and reference ranibizumab in the EU-relevant patient population.

Generally, the frequency and type of ocular adverse events (AEs) were comparable between the treatment groups, with most AEs of mild or moderate intensity, with no identifiable clinically relevant differences. Both drugs were well tolerated with no obvious safety concerns, with the safety profile of FYB201 consistent with the safety of the reference product. A total of 21.4% of FYB201 patients and 27.6% of reference ranibizumab patients experienced AEs linked to the IVT injection procedure.

The authors concluded by saying, “FYB201 can be considered biosimilar to reference ranibizumab in terms of clinical efficacy and local and systemic safety in the treatment of patients with newly diagnosed subfoveal nAMD. Biosimilar ranibizumab may offer a new treatment option for patients.”

Reference

Holz FG, Oleksy P, Ricci F, Kaiser PK, Kiefer J, Schmitz-Valckenberg S. Efficacy and safety of biosimilar FYB201 compared with ranibizumab in neovascular age-related macular degeneration. Ophthalmology. 2022;129(1):54-63. doi:10.1016/j.ophtha.2021.04.031