A recent study aimed to assess the safety of intravitreal ranibizumab biosimilar molecule (Razumab) treatment for chorioretinal diseases under real-world conditions.
Chorioretinal vascular diseases include age-related macular degeneration (AMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). These diseases are among the leading causes of vision impairment and blindness globally. The management of these diseases has been revolutionised over the last 16 years by the rapid, widespread adoption of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. At present, four anti-VEGF drugs have been approved for use by the FDA. These include ranibizumab and brolucizumab. To optimally treat retinal disorders, these drugs must be injected repeatedly over many years. However, this treatment regimen is expensive, which often prevents many patients from being able to start treatment. This outlines the need for a widely available, economical and effective anti-VEGF drug with an acceptable safety profile.
Biosimilar drugs for the treatment of chorioretinal diseases
Biosimilar drugs are those that are structurally and functionally similar to approved biological agents, which could be an important advance in the management of retinal disorders. Razumab is the first biosimilar of ranibizumab, and was approved by the Drug Controller General of India (DGCI) in 2015 after a phase III trial demonstrated its efficacy and safety in 103 eyes with nAMD and 160 eyes with macular edema due to RVO.
Intravitreal anti-VEGF drugs have been associated with ocular and systematic adverse events. The phase III RE-ENACT trial failed to identify any new safety concerns with intravitreal Razumab (IVRz) treatment. However, there were sporadic cases of sterile endophthalmitis with early production batches of the drug, which forced developers to modify the manufacturing process, resulting in no further incidents of sterile endophthalmitis after this change.
Overall, the data from the RE-ENACT trial suggests that IVRz is safe to use, but the small number of treated eyes (263 in total) may not be representative of outcomes from more widespread, real-world use of the drug for treatment of chorioretinal diseases. Therefore, this study reported the ocular and systemic safety profiles from the real-world use of IVRz in tertiary care centres in India over a period of 5 years.
Construction of the real-world study of Razumab safety
The researchers carried out a multicentre, retrospective chart review, which included patients from 15 centres receiving IVRz injections between 2016 and 2020. Patient demographics, ocular examination data, safety information regarding series adverse events (SAE) or serious adverse drug reactions (sADR), and non-serious AEs (nsAE) or non-serious ADR (nsADR) occurring within a month of IVRz injections were compiled. Collected data was analysed using Radical NewCharts Horizon and independently verified using scipy and numpy. Continuous variables were characterised with mean and standard variation, whereas categorical variables were characterised with frequencies and percentages. The rate of AEs was expressed as a fraction, with the denominator being the total number of injections.
Overall, a total of 6404 eyes from 6404 different patients received 9406 IVRz injections over the period of 4.25 years. Adverse events were reported after 1978 of the injections, equating to 21.03%. Out of the overall 21.03% adverse events the figure can be broken down into: 64.16% nsAE, 32.96% nsADR, 2.37% sADR, and 0.51% SAE. The most frequently reported adverse events were subconjunctival haemorrhage (reported in 8.2% of total injections), transient blurring of vision (6.5%), and mild ocular pain (5.27%). Serious ocular adverse events were rare, with only 31 cases of retinal pigment epithelial tears, two cases of non-infectious vitritis and one case of endophthalmitis. Systemic adverse events were also infrequent, with only seven patients experiencing non-fatal myocardial infarction and six patients presenting non-fatal cerebrovascular accident.
This study reports the largest pooled real-world safety data on IVRz use. Overall, the results did not raise any new safety concerns for the Razumab biosimilar agent, with the incidence and range of adverse reactions being similar to those reported with other anti-VEGF drugs. Therefore, this real-world evidence suggests that IVRz is a safe anti-VEGF agent for the treatment of chorioretinal diseases. However, long-term prospective studies with appropriate control groups are needed to validate the ocular and systemic safety of IVRz injections.
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