Severe asthma affects a minority of patients but drives a disproportionate share of healthcare costs for this condition. Although biologics have improved outcomes for allergic phenotypes, their high price limits equitable access. Emerging biosimilars offer similar efficacy at lower costs and promise broader availability. In his latest commentary, Dr João Gonçalves PhD examines key regulatory milestones, pivotal trials and strategies for integrating omalizumab biosimilars into clinical practice.
Asthma is a serious global health issue affecting all age groups and its prevalence is increasing in many countries.1 Between 5% and 10% of patients meet Global Initiative for Asthma (GINA) criteria for severe disease. Still, this subgroup accounts for approximately 60% of direct asthma expenditure owing to frequent exacerbations, hospitalisations and biologic therapy.1,2
Biosimilars are biologic drugs highly similar to an approved reference product, with no clinically meaningful differences in safety, purity or efficacy. Although minor variations in inactive components may occur, biosimilars undergo rigorous analytical, non-clinical and clinical testing to confirm comparable performance and therapeutic effect. They present a promising solution to the affordability challenges associated with high-cost biologics.
Omalizumab is a recombinant humanised monoclonal antibody that selectively binds to immunoglobulin E (IgE), preventing its interaction with the high-affinity FcεRI receptor found on mast cells, basophils and eosinophils. By blocking this critical step in the allergic inflammatory cascade, omalizumab mitigates downstream immune activation.
Omalizumab is approved in the UK and EU as an add-on therapy for the management of severe IgE-mediated asthma in adults and children over six years of age, and for moderate-to-severe allergic asthma in the US. More recently, it was also indicated for treating chronic spontaneous urticaria (CSU).3
Omalizumab has been shown to reduce asthma exacerbations by about 58%,4 lower oral-corticosteroid use and may also attenuate lung-function decline.5 Nevertheless, list price renders omalizumab cost-inefficient in many health systems.6
Asthma biosimilar regulatory milestones
The European Medicines Agency (EMA) granted central marketing authorisation for the omalizumab biosimilar Omlyclo, also known as CT-P39, in May 2024 after it met analytical, pharmacokinetic, pharmacodynamic and clinical comparability requirements. Some 10 months later, the US Food and Drug Administration (FDA) approved Omlyclo as the first interchangeable respiratory biosimilar, allowing pharmacy substitution in many states.
The omalizumab biosimilar Genolar has been marketed in the Russian Federation since 2022 on the strength of a domestic phase 3 asthma dossier. Zerafil (P043) has completed its pivotal trial in Iran and is currently undergoing national regulatory review.7
Key biosimilar clinical evidence
Legacy data from the originator product continues to set the benchmark. The INNOVATE trial8 demonstrated significant reductions in clinically significant exacerbations (26%) versus placebo when omalizumab was added to guideline-based therapy of high-dose inhaled corticosteroids and long-acting beta agonists. A later randomised trial confirmed benefits in patients inadequately controlled on standard treatment.9
The only published head-to-head trial comparing biosimilars to originator biologics in asthma to date is a phase 3 study from Iran.7 In this study, 256 adults with uncontrolled GINA step 4/5 allergic asthma were treated with weight- and IgE-adjusted doses of either Zerafil or reference omalizumab (brand name Xolair) over 28 weeks.
The protocol-defined exacerbation rate was 0.15 in the biosimilar group and 0.19 in the reference group. The resulting rate difference of –0.04 (95% CI 0.15–0.07) fell well within the prespecified equivalence margin, supporting the clinical similarity of the two treatments.7
Improvements in forced expiratory volume in one second and Asthma Control Test scores were comparable between the two groups. No anti-drug antibodies were detected, and the incidence of serious adverse events was lower in the Zerafil group.7
The Genolar study included 191 patients aged 18–75 years with moderate-to-severe atopic asthma that remained poorly controlled despite at least two months of advanced (GINA stage 4) treatment.10
Group 1, which consisted of 127 patients, received Genolar for 52 weeks, while 64 patients in Group 2 received the reference omalizumab. Dosages were based on each patient’s IgE level and body weight, with omalizumab given at 75–600 mg every two or four weeks.
The study’s primary endpoint was the proportion of patients rated as ‘excellent’ or ‘good’ on the Global Evaluation of Treatment Effectiveness (GETE) scale at 26 weeks.
The primary efficacy analysis showed that 57.4% of patients in Group 1 and 45.2% in Group 2 achieved a GETE score of ‘excellent’ or ‘good’ in the per-protocol population, but the difference was not statistically significant (p = 0.132).
Genolar was non-inferior to the reference drug and safety analysis showed that both drugs had a similar frequency of adverse events. Additionally, no anti-drug antibodies were detected, indicating no immune response to either treatment.10
Because CSU is considered a more immunologically sensitive model for IgE blockade than asthma, both the EMA and FDA accepted a CSU trial as the confirmatory study for Omlyclo.
The trial involved 533 patients and Omlyclo demonstrated therapeutic equivalence in the weekly Urticaria Activity Score (difference –0.71; 95% CI 1.97–0.55). Additionally, a switch to Omlyclo at Week 12 showed no loss of response, supporting its designation as an interchangeable product.11
Safety and immunogenicity
Across all biosimilar programmes, the safety profile mirrors that of the reference product. Injection-site reactions, headache and upper-respiratory infections remain the most common adverse events, and no grade ≥ 4 toxicities, anaphylaxis or neutralising antibodies have been reported.7,11
Omlyclo is subject to additional monitoring in the UK and Europe as part of post-authorisation obligations.
Economic considerations
In the seminal Asthma Policy Model, omalizumab added 1.7 quality-adjusted life-months at an incremental $131,000 over 10 years, giving an incremental cost-effectiveness ratio of $821,000 per quality-adjusted life-year, which is beyond conventional willingness-to-pay thresholds.6
Subsequent analyses in Europe, Asia and Latin America reached similar conclusions. They also showed that price reductions in the 25–40% range, typical for first-generation biosimilars, would bring incremental ratios below country-specific thresholds.2,12
Implementing biosimilars in practice
Interchangeability regulations vary across jurisdictions. In the US, pharmacists may dispense Omlyclo instead of the reference product without prior prescriber approval where state law permits. In the EU, substitution decisions reside with individual member states.
Biosimilars are supplied in the same vial or prefilled-syringe formats and follow identical weight- and IgE dosing charts, so electronic prescribing systems need to incorporate the new product codes to avoid errors.
Pharmacists and clinicians should document each injection’s brand name and batch number to ensure traceability and meet pharmacovigilance requirements. Patient counselling should emphasise that biosimilars have been approved based on rigorous comparability studies and are expected to deliver the same clinical benefit at a lower cost.
Conclusion
The scientific foundation underpinning omalizumab biosimilars has become increasingly robust. Zerafil provides direct asthma-specific confirmation of equivalence, Genolar corroborates these findings in a separate population and Omlyclo extends the paradigm to worldwide markets through CSU data, analytical concordance and regulatory extrapolation.
However, several knowledge gaps persist. Formal paediatric studies have yet to be conducted, despite regulatory extrapolation to children aged six years and older. Long-term open-label extensions beyond one year are necessary to confirm sustained efficacy and immunogenicity.
Real-world data on adherence, persistence and device usability would complement trial evidence.
Finally, next-generation anti-IgE agents such as ligelizumab may further influence pricing strategies and clinical positioning.
With anticipated price reductions of up to 40%, anti-IgE therapy could shift from a niche option to a broadly cost-effective standard for severe allergic asthma. Vigilant pharmacovigilance, clinician engagement and supportive policy will be pivotal to realising this therapeutic potential.
Author
João Gonçalves PharmD PhD
Faculty of Pharmacy, University of Lisbon, Portugal
References
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