Celltrion Biosimilar Demonstrates Equivalence With Xolair in Phase 1 Study

Celltrion Healthcare’s omalizumab biosimilar (CT-P39) demonstrated comparable safety and pharmacokinetic profiles compared with the reference product (Xolair; Genentech/Novartis) in healthy volunteers, according to a poster presentation from the American Academy of Allergy Asthma and Immunology’s annual meeting.

The investigators conducted the study in 2 parts. The first part included the assessment of initial safety of the biosimilar and the second part included the comparison of its pharmacokinetics to the reference product. The biosimilar was compared against the version of Xolair approved in the European Union and the version licensed for use in the United States.

Omalizumab is an anti-inflammatory agent that binds to free immunoglobulin E (IgE), resulting in the reduction of free IgE and the increase of total IgE in a patient’s system stemming from the formation of omalizumab-IgE complexes. The reference product is used to treat asthma and chronic idiopathic urticaria, a form of hives. There are currently no biosimilars for Xolair that are FDA-approved or authorized for use under the European Medicines Agency.

In total, 176 healthy patients between the ages of 18 and 55 years with a total IgE level of equal to or less than 100 IU/mL at screening were enrolled in the study, and were randomly assigned to receive a single subcutaneous 150 mg dose of CT-P39, EU-Xolair, or US-Xolair. The subjects were followed up to 127 days after they received their injection and 18 total blood samples were planned to be taken from each person for pharmacodynamic and pharmacokinetics analysis.

Overall, 62 subjects received the biosimilar, 64 received the European Union version of the reference product, and 50 were given the FDA-approved reference product. The mean age of the cohort was 27.8 years for the CT-P39 group, 30.9 years for the EU-Xolair group, and 30.3 years for the US-Xolair group. In all 3 groups, the majority of the subjects were women and White.

The pharmacodynamic profiles and serum concentrations of free IgE and total IgE were comparable between the groups. Although some numerical differences in pharmacodynamics were detected, the investigators said that they were likely driven by high inter-subject variation and deviating values. The mean serum concentrations of the biosimilar and reference drugs up to day 127 were also similar between the treatment groups.

The biosimilar group experienced a total of 87 treatment-emergent adverse events (TEAEs), with 19.4% of the cohort experiencing a headache and 14.5% experiencing an injection site reaction. The EU-Xolair group reported 115 TEAEs and the US-Xolair treatment arm reported 110 total TEAEs. Headaches and injection site reactions were experienced by 23.4% and 9.4% of the EU-Xolair subjects and 30.0% and 12.0% of the US-Xolair subjects, respectively.

Celltrion announced the launch of the phase 1 trial in 2019 and began testing CT-P39 in patients with chronic idiopathic urticaria in October 2020. The phase 3 trial was initiated after the Incheon, Republic of Korea-based company got the regulatory green light from the Republic of Korea’s Ministry of Food and Drug Safety to begin testing. The trial is being conducted across 65 sites in 7 countries and is expected to be completed half-way through 2023.

In addition to Celltrion, Selexis and Generium have an omalizumab biosimilar (Genolar), which was launched on the Russian market in February 2022 for the treatment of persistent atopic bronchial asthma and resistant chronic idiopathic urticaria for patients aged 6 years and older.

In April 2020, BiosanaPharma, a biotech company that operated in Australia, The Netherlands, and Singapore, also initiated a phase 1 study for its omalizumab biosimilar candidate (BP001). In February 2022, BiosanaPharma entered into a global licensing agreement with Alvotech Holdings for the omalizumab candidate.

Reference

Mclendon K, Wabnitz P, Kim S, et al. Pharmacodynamics of CT-P39, a proposed biosimilar of omalizumab, compared with EU-Xolair and US-Xolair; Result of a phase 1, randomized, double-blind, parallel group, single-dose study in healthy subjects. Presented at: AAAAI 2022; February 25-28, 2022; Phoenix, AZ. Abstract 586.