CT-P39: An Omalizumab Biosimilar.

Biologics and the treatment of chronic rhinosinusitis

Omlyclo (omalizumab-igec), the first FDA-approved biosimilar to omalizumab (Xolair) in the United States, was approved on 7 March 2025, for multiple indications including atopic asthma, chronic rhinosinusitis with nasal polyps, IgE-mediated food allergy, and chronic spontaneous urticaria (CSU). Functioning as an anti-IgE monoclonal antibody, Omlyclo binds free IgE, preventing its interaction with FcεRI receptors on mast cells and basophils, thereby reducing inflammatory responses. Clinical trials, including a pivotal global Phase 3 study in CSU, demonstrated comparable efficacy to Xolair with a significantly reduced cost, enhancing accessibility for patients. While generally well tolerated, reported side effects include pruritus, vertigo, and gastrointestinal disturbances, with rare concerns regarding malignancy risk requiring further long-term evaluation. The availability of this cost-effective biosimilar marks an important milestone in expanding biologic treatment access for patients with allergic asthma and CSU.

Omalizumab is a recombinant monoclonal antibody, targeting the epsilon 3 domain of free serum IgE antibodies, and thus preventing their attachment to the cognate high-affinity receptor on mast cells and reducing the number of cell-bound receptors. It represents the first ‘biological’ that has been studied in allergy and was registered several years ago for the treatment of severe allergic asthma in adults and children by the FDA and the EMA. About one year ago, omalizumab was registered for adult patients with chronic spontaneous urticaria – with or without angioedema – which is insufficiently controlled by standard treatment, including high-dose antihistamines. During the last years, international guidelines have profoundly changed our therapeutic approaches to chronic urticarial patients in which, instead of a previously recommended combination treatment with different histamine receptor antagonists, an increase of non-sedating H-1 receptor antagonists of the second generation up to a quadruple dose of the standard recommended regimen is now the general rule (1,2,3,4). These new recommendations have led to a remarkable improvement of response rates seen in urticarial patients; however, by far not all adult patients with chronic spontaneous urticaria are sufficiently controlled even by high doses of antihistamines. The application of omalizumab as a third-line option has demonstrated an unexpected additional benefit and leads to a complete relief of symptom in almost all treated patients. All three of the pivotal phase III studies in adults have led to a recommended dose of 300 mg omalizumab in 4 weeks, which differs from dose regimens for allergic asthma, where the patient's body weight and the total serum IgE levels determine the omalizumab dose. It seems that with the novel treatment option the vast majority of all adult patients with chronic spontaneous urticaria are adequately controlled without major safety problems, which is a remarkable step forward in the long-term treatment of urticaria. The problems of chronic urticaria in childhood seem to be inadequately perceived, which may be due to its low prevalence compared to adults. Until recently, the natural course of CU has not really been studied in large cohorts of children. A recent prospective study from Thailand suggests that chronic urticaria in children has a more favorable outcome than in adults, with a remission rate of 18.5% after one year and 54% after 3 years 5. Like adults, more than 30% of the children with a chronic spontaneous urticaria were found to have autoantibodies to the alpha subunit of the high-affinity IgE receptor (Fc-epsilon-R 1) and/or anti-IgE antibodies. The presence of these autoantibodies may be screened for by performing the autologous serum skin test (ASST). Up to now, the intervention with the recombinant monoclonal antibody omalizumab has been studied in childhood only for severe asthma as well as in rhinitis. In most parts of the world, it is registered for the treatment of uncontrolled severe asthma after the age of six. A systematic review on the use of omalizumab in children, which appears in this issue, indicates that the addition of omalizumab in patients with uncontrolled allergic asthma can be considered as effective and safe 6. Up to now, there is not a single randomized controlled trial in children with urticaria. Therefore, the different case reports presented in this issue reporting a beneficial effect in refractory solar urticaria, and in spontaneous and physical urticaria are very encouraging and of high interest (7,8,9). Although very severe clinical cases of uncontrollable chronic urticaria compared to adults seem to be rare and the outcome may be more favorable in childhood, the information presented here strongly suggests that the pathophysiologic mechanism leading to chronic urticaria in childhood may be similar. It appears that the time has come to ask for randomized controlled trials with omalizumab and possibly other biologics for an apparently forgotten disorder in childhood which may deserve more attention and consideration than given in the past.

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BACKGROUND: Chronic urticaria is a skin disease characterized by the appearance of itchy weals and/or angioedema for 6 or more weeks. Chronic urticaria is subdivided into chronic spontaneous urticaria, which occurs due to an unknown cause, and chronic inducible urticaria, which occurs as a result of exposure to various physical factors (water, cold, heat, pressure, mechanical irritation), can occur simultaneously or independently of each other. Omalizumab, anti-IgE monoclonal antibody, is approved for the treatment of patients with chronic spontaneous urticaria and is the second choice in cases of resistance to antihistamine treatment. In patients with a combination of chronic spontaneous urticaria and chronic inducible urticaria, the effectiveness of treatment with omalizumab has been little studied.
 AIM: compare the effectiveness of omalizumab treatment in patients with chronic spontaneous urticaria and patients with a combination of chronic spontaneous and chronic induced urticaria.
 MATERIALS AND METHODS: Under supervision there were 30 patients with chronic spontaneous urticaria and combined chronic spontaneous and inducible urticaria (15 patients in each group). Evaluation of the effectiveness of treatment was carried out according to the results of the questionnaires DLQI (dermatological index of quality of life), CU-Q2oL (questionnaire for quality of life in chronic urticaria), UCT (urticaria control test), UAS (urticaria activity scale), HADS (Hospital Anxiety and Depression Scale) and provocation tests in dynamics before and during treatment.
 RESULTS: All patients received omalizumab 300 mg subcutaneously once a month for 6 to 12 months. After the first injection of omalizumab, we noted a decrease in the severity of urticaria, an increase in the level of disease control and quality of life when comparing parameters before and during treatment in more than 90% of patients. Improved performance remained at this level throughout all subsequent months of treatment.
 CONCLUSION: Omalizumab is equally effective in patients with an isolated form of chronic spontaneous urticaria and in patients with a combined form of chronic spontaneous and inducible urticaria. The use of omalizumab allows you to control the symptoms of chronic spontaneous and inducible urticaria, even with prolonged use.

The article describes a modern approach to the use of anti-IgE therapy for allergic bronchial asthma and conditions associated with this disease. The humanized monoclonal anti-IgE antibody, Omalizumab (Xolar®), is a promising treatment for allergic diseases mediated by IgE. Much evidence has been obtained of the effectiveness of Omalizumab in allergic bronchial asthma and chronic spontaneous (idiopathic) urticaria, on the basis of which global meta-analyzes have been carried out confirming the effectiveness and safety of this therapeutic strategy. Recent scientific articles actively discuss the possibility of expanding indications for the medical use of Omalizumab. Clinical studies have been published on the efficacy and safety of Omalizumab for allergic rhinitis, allergic keratoconjunctivitis, chronic rhinosinusitis, nasal polyps, chronic idiopathic urticaria, food allergies, allergen-specific immunotherapy, atopic dermatitis, allergic bronchopulmonary aspergillosis – in cases of comorbidity with asthma. The clinical effect of Omalizumab in patients with allergic bronchial asthma is the most studied and proven. Currently, a number of clinical studies evaluate the long-term results of prolonged use of Omalizumab or the condition after its cancellation in patients with allergic bronchial asthma and various comorbidity.

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Background. Omalizumab, a recombinant humanized anti-IgE antibody, is an effective treatment option for patients with antihistamine-resistant chronic spontaneous urticaria (CSU). 14–36 % of CSU patients have concomitant chronic inducible urticaria (CIndU). However, it is unclear whether CSU patients with comorbid CIndU can benefit from this treatment.Aim of the study. To assess the efficacy and safety of omalizumab in two patients with CSU and several of types of concomitant CIndU.Materials and methods. CSU and CIndU were diagnosed as recommended by the international urticaria guideline. Both female patients were treated with omalizumab 300 mg by subcutaneous injection every 4 weeks. Response to treatment was assessed by a carefully determined history, the urticaria activity score, urticaria control test, and results of provocation testing.Results. Symptoms of both CSU and CIndU decreased dramatically during the first week of treatment. No adverse events were documented.Conclusions. Omalizumab may be an effective treatment option for patients with combination of antihistamine-resistant CSU and concomitant CIndU. Our findings should be confirmed in larger prospective studies.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory disease of the nasal and sinus mucosa. This inflammatory process is supported by a multitude of cytokines, including IL-4, IL-5, and IL-13 produced by Th2 cells, as well as by IgE produced by B lymphocytes in response to a stimulus. Omalizumab is an anti-IgE monoclonal antibody with well-recognized roles in allergic asthma and chronic spontaneous urticaria. The aim of this study was to evaluate the clinical efficacy of omalizumab in a cohort of 13 patients suffering from chronic rhinosinusitis with CRSwNP. The inclusion criteria considered were as follows: 18 years of age, with a diagnosis of chronic rhinosinusitis with severe nasal polyposis expressed by an NPS greater than or equal to 5 and/or a SNOT-22 greater than or equal to 50. In addition, in the enrolled patients, the classic treatment with corticosteroids had to have been suspended due to recurrence after surgery or lack of response. Our results highlighted that omalizumab treatment for 16 weeks improved the parameters analyzed: SNOT-22, NPS, NRS, and NCS. The clinical efficacy of omalizumab was further strengthened by a significant improvement in respiratory function as well as reductions in the nasal polyps' size and in the associated symptoms.

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