Omalizumab Biosimilar Matches Reference Product in Chronic Spontaneous Urticaria

CT-P39, an omalizumab biosimilar, and reference omalizumab demonstrated comparable efficacy, pharmacokinetics, pharmacodynamics, safety, and immunogenicity, as well as quality of life impact, in patients with chronic spontaneous urticaria, as confirmed by a 16-week follow-up of a phase 3 trial.1

CT-P39, also known as Omlyclo, was approved by the European Medicines Agency in May 2025 as the first omalizumab biosimilar.2 The biosimilar was also approved by Health Canada in December 2024 and the FDA in March 2025.3,4

The present international, multicenter, double-blind, randomized, active-controlled, parallel-group study, published in Clinical and Translational Allergy, sought to confirm that Omlyclo can perform with the same safety and efficacy as the original product.1 Access to omalizumab, an effective biologic for chronic spontaneous urticaria, can be limited by its high cost, prompting the development of biosimilars like CT-P39 to improve affordability and access. According to Novartis’ financial records, global sales for reference omalizumab (Xolair) in 2024 amounted to $4.4 billion, making it the seventh highest-grossing immunology product in the world.5,6

The study involved 619 patients with chronic spontaneous urticaria across two 12-week treatment periods and a 16-week follow-up, in which patients received subcutaneous injections of either CT-P39 or reference omalizumab at 150-mg or 300-mg doses, with rerandomization or dose escalation in the second period. Throughout the study, efficacy, quality of life, pharmacokinetics, pharmacodynamics, safety, and immunogenicity were assessed using patient-reported outcomes, clinical monitoring, and blood analyses, with results summarized descriptively through week 40.

Of the 619 patients randomized, 554 (89.5%) entered the 16-week follow-up phase, and 518 (83.7%) completed the full study through week 40, with completion rates ranging from 80.6% to 88.7% across all treatment groups. Discontinuation rates and reasons were similar between groups, with the most common reason during follow-up being categorized as “other.”

Efficacy outcomes such as weekly itch severity scores, urticaria activity scores, and hives severity scores improved significantly during the 24-week treatment periods, which gradually declined during follow-up but remained better than baseline values, with no clinically meaningful differences between CT-P39 and reference omalizumab groups. At week 40, the number of antihistamine tablets used as rescue therapy remained lower than baseline in all groups, and fewer than 10% of patients in any group required an additional nonsedating H1-antihistamine as background therapy. Improvements in quality-of-life measures, including Dermatology Life Quality Index and Chronic Urticaria QoL Questionnaire, followed a similar pattern—peaking during treatment and partially declining by week 40, yet not returning to baseline levels.

Pharmacokinetic data showed a dose-related increase in omalizumab serum trough concentrations during treatment, followed by a gradual decrease after treatment cessation, with end-of-study mean concentrations ranging from 2.74 µg/mL (initial reference product 300-mg maintenance group) to 4.11 µg/mL (reference omalizumab 150-mg group). Pharmacodynamic results demonstrated a 2- to 3-fold increase in total immunoglobulin E (IgE) during treatment, with levels gradually decreasing during follow-up, while free IgE, which decreased during treatment, began to return to baseline after week 24 in all groups.

Safety profiles were consistent across groups during the follow-up period, with similar proportions of patients experiencing at least 1 treatment-emergent adverse event (TEAE). The most frequently reported TEAEs (≥ 2%) were COVID-19, headache, nasopharyngitis, tonsillitis, and upper respiratory tract infection. Serious TEAEs occurred in up to 3.1% of patients in any group and were considered unrelated to the study drug. No deaths, anaphylactic reactions, serum sickness, or parasitic infections were linked to the study treatment. One patient died by suicide, previously reported and determined unrelated to the drug. Injection-site reactions, the most common related TEAE, occurred only during the treatment period.

Immunogenicity analysis showed that the majority of patients tested negative for antidrug antibodies at week 40. Antidrug antibody positivity rates were 6.9% in the CT-P39 300-mg group, 1.5% in the reference omalizumab 300-mg group, 3.1% in the switched group (ref-OMA to CT-P39), 0% in the reference omalizumab maintenance group, 6.5% in the CT-P39 150-mg group, and 1.9% in the reference omalizumab 150-mg group.

The authors stated, “The overall safety profile of CT-P39 continues to be consistent with the known safety profile of omalizumab, with no new or unexpected concerns during the whole study period and no new safety findings, including after switching to CT-P39 from [reference omalizumab].”

References

1. Grattan C, Dytyatkovska Y, Springer M, et al. Efficacy and safety of CT-P39, an omalizumab biosimilar, in chronic spontaneous urticaria: 16-week follow-up study. Clin Transl Allergy. June 2, 2025. Accessed June 24, 2025. doi:10.1002/clt2.70069

2. Celltrion receives European Commission approval of Omlyclo (CT-P39), the first and only omalizumab biosimilar approved in Europe. Press release; Celltrion. May 24, 2025. Accessed June 23, 2025. https://celltrion.com/en-us/company/media-center/press-release/3246

3. Jeremias S. Health Canada approves first omalizumab biosimilar. The Center for Biosimilars®. December 16, 2024. Accessed March 7, 2025. https://www.centerforbiosimilars.com/view/health-canada-approves-first-omalizumab-biosimilar

4. Jeremias S. FDA approves first omalizumab biosimilar. The Center for Biosimilars. March 7, 2025. Accessed June 24, 2025. https://www.centerforbiosimilars.com/view/fda-approves-first-omalizumab-biosimilar

5. Novartis annual report 2024. Novartis. January 30, 2025. Accessed June 23, 2025. https://www.novartis.com/sites/novartiscom/files/novartis-annual-report-2024.pdf

6. Rashid A, Shashikumar S, Xie V, Kovacevic V. Top 10 best-selling immunology drugs by recent sales data. Xtalks. January 2, 2025. Accessed June 23, 2025. https://xtalks.com/top-10-best-selling-immunology-drugs-by-recent-sales-data-4025/