Sandoz's Cimerli (ranibizumab-eqrn) has emerged as a significant advancement in the treatment of ocular conditions, offering patients a new therapeutic option as the first and only FDA-approved interchangeable biosimilar to Genentech's Lucentis (ranibizumab).
The recombinant humanized monoclonal antibody fragment functions as a vascular endothelial growth factor (VEGF) inhibitor, providing treatment for several eye and retinal vascular disorders. Cimerli received FDA approval on August 2, 2022, and became commercially available in the United States on October 3, 2022.
Understanding the Target Conditions
Age-related macular degeneration (AMD) affects more than 19.8 million Americans aged 40 or older, with higher prevalence among women and increasing incidence with age. Neovascular AMD (nAMD), a serious subtype, occurs when abnormal blood vessels grow underneath the retina, potentially causing blood or fluid leakage that results in macula scarring and accelerated vision loss.
Patients with nAMD typically experience blurred central vision, distortion of straight lines, difficulty seeing fine details at close range, and decreased ability to recognize faces or read. This condition primarily affects individuals aged 50 and older.
Mechanism of Action and Clinical Applications
Cimerli binds with high affinity to the receptor's binding domain of active VEGF-A, preventing interaction between VEGF-A and its cell surface receptors (VEGF receptor 1 and VEGF receptor 2). This inhibition reduces endothelial cell proliferation, vascular leakage, and formation of new blood vessels, effectively slowing disease progression to preserve vision.
The biosimilar is indicated for multiple ocular conditions:
- Neovascular age-related macular degeneration
- Macular edema after retinal vein occlusion
- Diabetic macular edema
- Diabetic retinopathy
- Myopic choroidal neovascularization
Biosimilar Status and Interchangeability
As a biosimilar, Cimerli demonstrates biological function, pharmacokinetics, pharmacodynamics, safety, immunogenicity, drug stability, and drug purity comparable to Lucentis with no clinically meaningful differences. To achieve interchangeability status, Cimerli was shown to have low complexity, a low incidence of immunogenicity, and comparable serious adverse effects to the reference product.
The biosimilar maintains the same formulations, amino acid sequencing, indications, and dosage strengths as Lucentis, ensuring consistent therapeutic outcomes.
Dosing and Administration
Dosing regimens for Cimerli vary based on the condition being treated:
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For neovascular AMD, macular edema after retinal vein occlusion, or myopic choroidal neovascularization: 0.5 mg administered by intravitreal injection once every 28 days (with a maximum treatment duration of 3 months for myopic choroidal neovascularization)
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For diabetic macular edema or diabetic retinopathy: 0.3 mg administered by intravitreal injection every 28 days with no maximum usage duration
All administrations must be performed by qualified ophthalmic healthcare providers under sterile conditions.
Safety Considerations
Cimerli is contraindicated in patients with ocular or periocular infection or hypersensitivity to ranibizumab products. Caution is advised for patients with cardiovascular disease history.
Common ocular adverse effects include:
- Conjunctival hemorrhage
- Eye pain
- Vitreous floaters
- Increased intraocular pressure
Non-ocular adverse effects may include nasopharyngitis, anemia, nausea, and cough. Clinicians should monitor intraocular pressure before and after injection, as increases may occur with ranibizumab products.
Market Impact
The introduction of Cimerli represents a significant development in ophthalmology, offering an interchangeable alternative to Lucentis for patients with various ocular conditions. As the first interchangeable biosimilar in this therapeutic area, Cimerli may improve access to treatment while maintaining the established efficacy and safety profile of the reference product.
