Biosimilarity Study for New Ranibizumab Biosimilar for Treating Neovascular (Wet) AMD
Introduction
Vascular endothelial growth factor-A (VEGF-A) inhibitors currently represent the standard of care for most cases of newly occurring, symptomatic neovascular age-related macular degeneration (nAMD). Ranibizumab, a recombinant humanized, monoclonal antibody fragment that binds to and neutralizes active isoforms of VEGF-A, has been approved for the treatment of nAMD. Considering the relatively high cost of original biological molecules, biosimilars are used very often. Biosimilarity studies have an important role in demonstrating the similarity of a biosimilar to the innovator molecule in terms of quality and molecular attributes.
Aim
To establish the clinical biosimilarity and interchangeability of a ranibizumab biosimilar with the reference innovator product
Patients Profile
- Patients with neovascular (wet) AMD (n=159)
- All the study subjects had active primary or recurrent subfoveal lesions with classic or occult choroidal neovascularization (CNV) secondary to AMD.
Methods
Study Design
- An active-controlled, parallel- group, comparative randomized, double blind, clinical study conducted across 16 hospitals in India
Treatment Strategy
- The initial double-blind period of 16 weeks was followed by an open-label phase till week 24
- Patients received either biosimilar (n=107) or reference ranibizumab (n=53) 0.5 mg (0.05 mL of 10 mg/mL solution) as an intravitreal injection once every 4 weeks for the treatment period of 24 weeks.
Outcomes
Primary Outcome
- Prevention of vision loss (determined as the proportion of patients who lost fewer than 15 letters in visual acuity at week 16 compared with baseline)
Secondary Outcomes
- Proportion of patients who lost fewer than 15 letters and who gained at least 15 letters in visual acuity from baseline to week 24
- Mean change in best corrected visual acuity (BCVA; no. of letters) from baseline to week 24
- Change in central macular thickness from baseline to week 24 [as assessed by optical coherence tomography (OCT)]. OCT was performed at screening, week 4, 8, 12, 16, 20 and 24.
- Immunogenicity
- Safety and tolerability (adverse events)
Results
- The mean age of the study subjects in the biosimilar arm was 67.04 years and of those in the reference arm was 67.06 years. The study was completed by 141 subjects (91 in the biosimilar arm and 50 in the reference arm).
- In the biosimilar test arm, 104 (98.11%) and 105 (99.06%) patients lost fewer than 15 letters in visual acuity at week 16 and week 24, respectively, versus. 53 (100%) at both follow-ups in reference arm.
- In the biosimilar arm, 27 (25.47%) and 34 (32.08%) patients gained at least 15 letters in visual acuity till week 16 and week 24 respectively, versus. 17 (32.08%) and 23 (43.30%) in the reference arm.
- The mean change in central macular thickness at 24 weeks was −89.93 ?m in the biosimilar arm versus. −64.42 ?m in the reference arm.
- The changes observed for the study outcomes did not differ statistically at 16 and 24 weeks in both the study groups.
- Of 38 adverse events reported during the study, 26 were reported in the biosimilar arm and 12 in the reference arm
- Immunogenicity samples tested negative for anti-drug antibodies against ranibizumab for all study subjects.
Conclusion
- The efficacy, safety and immunogenicity profile of the biosimilar ranibizumab formulation was comparable with that of the innovator reference product.
- The indigenous ranibizumab biosimilar may thus be considered as a viable alternative to the reference innovator product for treating patients with neovascular (wet) AMD.
Clinical Ophthalmology 2021:15 3087–3095.
