Efficacy and safety of a proposed omalizumab biosimilar compared to the reference product in the management of uncontrolled moderate-to-severe allergic asthma: a multicenter, phase III, randomized, double-blind, equivalency clinical trial

Front Immunol. 2024 Jul 29:15:1425906. doi: 10.3389/fimmu.2024.1425906. eCollection 2024.

Abstract

Background and aims: Allergic asthma has a considerable burden on the quality of life. A significant portion of moderate-to-severe allergic asthma patients need omalizumab, an anti-immunoglobulin-E monoclonal antibody, as an add-on therapy. In this phase III clinical trial P043 (Zerafil®, CinnaGen, Iran) efficacy, safety, and immunogenicity were compared with Xolair® (the originator omalizumab). The primary outcome was the rate of protocol-defined asthma exacerbations.

Methods: Exacerbation rates, Asthma Control Test (ACT) results, spirometry measurements, immunogenicity, and safety were evaluated. Each subject received either medication with a dose ranging from 150 to 375 mg based on pre-treatment serum total IgE level (IU/mL) and body weight (kg) every two or four weeks for a duration of 28 weeks.

Results: Exacerbation rates were 0.150 (CI: 0.079-0.220) in the P043 group, and 0.190 (CI: 0.110-0.270) in the omalizumab group (per-protocol). The least squares mean differences of predicted Forced Expiratory Volume in the First second (FEV1) were -2.51% (CI: -7.17-2.15, P=0.29) and -3.87% (CI: -8.79-1.04, P=0.12), pre- and post-bronchodilator use. The mean ± SD of ACT scores at the screening and the last visit were 10.62 ± 2.93 and 20.93 ± 4.26 in P043 and 11.09 ± 2.75 and 20.46 ± 5.11 in the omalizumab group. A total of 288 adverse events were reported for the 256 enrolled participants. Among all, "dyspnea" and "headache" were the most reported ones. The overall incidence of adverse events (P=0.62) and serious adverse events (P=0.07) had no significant differences between the two groups. None of the samples were positive for anti-drug antibodies.

Conclusion: P043 was equivalent to omalizumab in the management of asthma in reduction of exacerbations. There was no significant difference in other efficacy and safety parameters.

Clinical trial registration: www.clinicaltrials.gov (NCT05813470) and www.IRCT.ir (IRCT20150303021315N20).

Keywords: IgE; allergic; asthma; biosimilar; omalizumab.

Publication types

  • Clinical Trial, Phase III
  • Equivalence Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Anti-Asthmatic Agents* / adverse effects
  • Anti-Asthmatic Agents* / therapeutic use
  • Asthma* / drug therapy
  • Biosimilar Pharmaceuticals* / adverse effects
  • Biosimilar Pharmaceuticals* / therapeutic use
  • Double-Blind Method
  • Female
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Male
  • Middle Aged
  • Omalizumab* / adverse effects
  • Omalizumab* / therapeutic use
  • Severity of Illness Index
  • Therapeutic Equivalency
  • Treatment Outcome
  • Young Adult

Substances

  • Anti-Asthmatic Agents
  • Biosimilar Pharmaceuticals
  • Immunoglobulin E
  • Omalizumab

Associated data

  • ClinicalTrials.gov/NCT05813470

Grants and funding

The author(s) declare financial support was received for the research of this article.