AUTHOR=Ghanei Mostafa , Ghalebaghi Babak , Sami Ramin , Torabizadeh Mehdi , Mirsadraee Majid , Amra Babak , Tavakol Marzieh , Raji Hanieh , Fallahpour Morteza , Kiani Arda , Abedini Atefeh , Jabbari Azad Farahzad , Mahdaviani Seyed Alireza , Attaran Davood , Samet Mohammad , Tavana Sasan , Haddadzadeh shoushtari Maryam , Nazari Javad , AghaeiMeybodi FatemehAlsadat , Fazlollahi Mohammad Reza , Ghasemi Ramin , Sabzvari Araz , Kafi Hamidreza , Idani Esmaeil TITLE=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 JOURNAL=Frontiers in Immunology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1425906 DOI=10.3389/fimmu.2024.1425906 ISSN=1664-3224 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).