Sandoz, a division of Novartis Group, announced positive data from the MYLIGHT phase 3 confirmatory efficacy and safety study assessing biosimilar aflibercept for the treatment of wet age-related macular degeneration (AMD).
Refresh me on the company.
Based in Switzerland and established in 2003 by Novartis, Sandoz specializes in generic pharmaceuticals and biosimilars with the intent to develop and commercialize novel, affordable therapeutics to address unmet medical needs. Historically, the Sandoz brand can be traced back to 1886 as Kern & Sandoz with an original focus on the production of dyes.
To note, in 2022, Novartis launched Sandoz as a stand-alone, publicly traded company via a 100% spin-off.
Dive more into its biosimilar background.
Since the company launched its first biosimilar in 2006, it has marketed eight biosimilars (in immunology, endocrinology, and oncology) and a further 24 assets in the clinical development stage.
Per Sandoz, the goal of biosimilar development is to confirm a potential candidate that matches its reference medicine in safety, efficacy, and quality.
Learn more here, including how the biosimilar development stage differs from reference medicines.
Now this candidate.
Aflibercept, the active compound in SOK583A1, is indicated to potentially improve visual acuity (VA) in patients with wet AMD, diabetic macular edema (DME), macular edema secondary to retinal vein occlusion (RVO), and other specific neovascular retinal diseases.
It works by binding and inhibiting ocular vascular endothelial growth factor (VEGF)-A as well as preventing abnormal blood vessel growth within the choroid (which can impact visual function).
And this phase 3 study?
The multicenter, randomized double-masked, two-arm, parallel MYLIGHT phase 3 study (NCT04864834)— part of Sandoz’s comprehensive late-stage biosimilar development program Sandoz—evaluated the use of SOK583A1 to Eylea (aflibercept; Regeneron Pharmaceuticals, Bayer AG) in 485 patients (ages 50+ years) across 20+ countries.
What was the patient criteria?
Eligible patients were required to have:
- A study eye diagnosed with active choroidal neovascularization (CNV) lesions (type 1 and/or 2) secondary to AMD and/or retinal angiomatous proliferation lesions (type 3)
- Total area of CNV comprising >50% of the total lesion area in the study eye
- A best-corrected visual acuity (BCVA) between 73 and 38 letters in the study eye
See here for the complete criteria as well as exclusion criteria.
How about the dosages?
Patients were randomized into four groups to receive an intravitreal injection of either:
- Group 1: SOK583A1 (40 mg/mL)
- 2 mg administered in study eye every 4 weeks at baseline, Week 4, Week 8
- After Week 8, administration every 8 weeks:
- Week 16, 24, 32, 40, 48
- Group 2: Eylea (European Union approved) (40 mg/mL)
- 2 mg administered in study eye every 4 weeks at baseline, Week 4, Week 8
- After Week 8, administration every 8 weeks:
- Week 16, 24, 32, 40, 48
What was measured?
The primary outcome measure, taken from baseline to Week 8, included:
- BCVA assessed using an Early Treatment of Diabetic Retinopathy Study (ETDRS) chart (at an initial distance of 4 meters).
Secondary outcome measures included:
- SOK583A1 anatomical outcome vs Eylea from:
- Week 1, 4, 8, 24, and 52; measured by the mean change in:
- Central subfield thickness (CST) via spectral domain-optical coherence tomography (SD-OCT)
- Baseline to Week 8 and 52; measured by the mean change in:
- Choroidal neovascularization (CNV) lesion size using fundus angiography (FA)
- Week 1, 4, 8, 24, and 52; measured by the mean change in:
- SOK583A1 vs Eylea efficacy for BCVA at Week 24 and 52.
- SOK583A1 vs Eylea safety for BCVA at Week 52.
- SOK583A1 vs Eylea immunogenicity for BCVA at Week 24.
- Systemic exposure of SOK583A1 and Eylea in patients undergoing the pharmacokinetic (PK) assessment.
Note, the PK assessment studies a drug’s journey from the time of its administration to its elimination, and involves four steps: absorption, distribution, metabolism, and excretion.
Findings?
According to Sandoz, the study met its primary efficacy endpoint, effectively confirming that—based on the two drugs’ safety, immunogenicity, and PK assessments—”there is no clinically meaningful difference between the two products.”
Significance?
With no significant difference between the biosimilar aflibercept and Eylea, these findings support the company’s intent to provide an affordable alternative medication for wet AMD patients.
To note, this biosimilar is just one of four the company is planning to launch within the next few years.
What’s next?
Sandoz is expecting to file for regulatory approval with the FDA (in the United States) and the European Medicines Agency (EMA) (in the European Union [EU]) in the coming months.