Phase 3 Trial Suggests Equivalence Between Biosimilar CKD-701 and Reference Ranibizumab in nAMD

Article

A phase 3 analysis found that CKD-701, a ranibizumab biosimilar candidate developed by CKD Limited, has comparable clinical efficacy and safety with the reference product (Lucentis) in patients with neovascular age-related macular degeneration (nAMD).

The candidate ranibizumab biosimilar CKD-701 (CKD Limited) met predefined equivalence criteria in a phase 3 clinical trial compared to the reference product (Lucentis) for treatment-naïve neovascular age-related macular degeneration (nAMD). Secondary endpoints and indicators of safety and immunogenicity were also comparable between groups, according to the investigators.

Therapies for nAMD, including ranibizumab, primarily target vascular endothelial growth factor (VEGF). Ranibizumab is a monoclonal antibody fragment that binds to and neutralizes active VEGF-A. It was originally approved in the United States in 2005.

The trial, published in PloS One, was conducted in 25 hospitals across the Republic of Korea in 312 patients who had newly-diagnosed subfoveal choroidal neovascularization secondary to AMD. Patients were randomized to receive intraocular injections of the biosimilar or originator monthly for three months followed by pro re nata dosing for nine months. A total of 277 patients completed the study, 135 in the biosimilar group and 142 in the reference product group.

The primary efficacy endpoint was the proportion of patients who lost fewer than 15 letters of best-corrected visual acuity (BCVA) between baseline and three months. Secondary endpoints included the presence of retinal fluid, changes in BCVA, and changes in central retinal thickness (CRT).

Efficacy endpoints similar between groups

In the biosimilar group, 143 (98.95%) patients had lost fewer than 15 letters of BCVA at 3 months, compared to 143 (98.62%) in the reference product group. The difference between groups was 0.66% (95% CI, -3.63–2.32), which fell within the predetermined equivalence range of -11.5% to 11.5%. There was also no significant difference between groups in BCVA at 6 and 12 months.

The authors said that the secondary efficacy endpoints assessed at 3, 6, and 12 months were also similar between groups, with no significant differences between treatment with CKD-701 and the reference product. Improvement of at least 15 letters in BCVA was achieved in 16%, 22%, and 25% of patients in the biosimilar group at 3, 6, and 12 months compared to 17%, 20%, and 21% in the originator group. Both groups demonstrated “significantly decreased CRT at all time points,” with no significant differences between groups. There was also no significant difference between the number of injections administered between groups.

Immunogenicity and Safety

Up to 12 months, the authors said, there was a “low cumulative incidence” of anti-drug antibodies (ADAs), which was similar between groups: 2 patients in the reference product group developed ADAs and no patients in the biosimilar group.

Adverse events occurred in about half of patients who received at least 1 dose of the study medication; 51% of patients receiving the biosimilar and 50% of those receiving the originator. Serious adverse events were reported in 16 patients (10%) in the biosimilar arm and 17 (10%) in the reference product arm. Serious adverse drug reactions occurred in 2 patients treated with the biosimilar and 3 patients treated with the reference product. There were no significant differences in adverse events between groups.

The investigators said their study demonstrated the equivalence of the candidate biosimilar CKD-701 to reference ranibizumab in efficacy, safety, and immunogenicity in patients with nAMD. Given the high cost of originator biologics, they said that CKD-701 is a “viable alternative” and anti-VEGF biosimilars including CKD-701 could “expand accessibility to anti-VEGF treatment and improve eventual treatment outcomes in the context of public ophthalmic healthcare.”

Reference

Yoon CK, Oh J, Bae K, Park UC, Yu KS, Yu HG. Efficacy and safety of a new ranibizumab biosimilar CKD-701 using a pro re nata treatment regimen in neovascular age-related macular degeneration: a phase 3 randomized clinical trial. PLoS One. 2022;17(11):e0275611. doi:10.1371/journal.pone.0275611

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