ABSTRACT
BACKGROUND: Chronic spontaneous urticaria (CSU) is a debilitating affliction that affects diverse quality of life (QoL) parameters such as sleep, self-esteem, and daily activities. Second-generation antihistamines, such as desloratadine, are more effective and safer in managing CSU. Desloratadine is a nonsedating, potent, and highly selective H1 receptor antagonist. At its daily dose of 5 mg, almost half of CSU patients do not show symptomatic improvement. European Academy of Allergy and Clinical Immunology (EAACI)/Global Allergy and Asthma European Network (GA2LEN)/European Dermatology Forum (EDF) (EuroGuiDerm)/Asia Pacific Association of Allergy, Asthma and Clinical Immunology (APAAACI) guidelines recommend increasing the dosage to up to four times in such nonresponsive patients. However, there is insufficient clinical evidence in Indian settings. METHOD: We evaluated the efficacy and safety of 10 mg desloratadine (OD) in 256 nonresponsive patients with moderate to severe CSU. The primary outcome was the change in Urticaria Activity Score (UAS7) from baseline to four weeks. Additionally, change in Chronic Urticaria Quality of Life (CU-Q2oL) scores during the course of treatment was also evaluated. RESULT: The mean UAS7 scores showed a significant reduction from 31.9 ± 4.8 at baseline to 18.2 ± 8.1 at the end of the study (p < 0.0001). The use of a higher dose of desloratadine also decreased the CU-Q2oL scores significantly from 59.8 ± 14.7 at baseline to 35.4 ± 10 at four weeks (p < 0.0001). The incidence of adverse events (AEs) possibly linked to the drug was low (1.6%), and no serious adverse events were reported. CONCLUSION: Results indicated improvements in the disease severity as well as its positive impact on participants' QoL. This study confirms the efficacy and safety of daily use of a twofold dose of desloratadine in nonresponsive moderate to severe CSU patients.
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INTRODUCTION: There is growing interest in the development of multiple presentations for biological products for subcutaneous (SC) injection for life cycle management and product differentiation. Bridging clinical studies are required to extrapolate the existing data package to new presentations. AREAS COVERED: This review compiles information of bridging clinical studies conducted for biological products administered by the SC route and approved in more than one presentation by the United States Food and Drug Administration's Center for Drug Evaluation and Research up until 31 December 2021. Information regarding indication(s), presentation(s), approval pathways, approval timelines, and various aspects of bridging clinical studies was collected from published documents. EXPERT OPINION: The type of bridging clinical study can depend on the extent of differences between presentations, existing data packages, and the stage of the product development. Design of a bridging clinical study should be based on the characteristics of a biological product and should be aimed at detecting the relevant differences between presentations. Single-dose comparative pharmacokinetics in normal healthy volunteers is the most common bridging clinical study design. Covariates like body weight and injection site should be considered during the design of these studies. The impact of the different user interfaces of presentations should also be considered.
Subject(s)
Biological Products , Drug Approval , United States , Humans , United States Food and Drug Administration , Biological Products/adverse effects , Pharmaceutical PreparationsABSTRACT
PURPOSE: The study was undertaken for regulatory purposes to establish clinical biosimilarity and interchangeability of a ranibizumab biosimilar with reference product. PATIENTS AND METHODS: A total of 159 subjects with neovascular (wet) age-related macular degeneration (AMD) were dosed with ranibizumab. Initial double blind period of 16 weeks was followed by open-label phase till week 24. Efficacy assessment was performed at weeks 1, 4, 8, 12, 16, 20 and 24 based on best corrected visual acuity. Change in central macular thickness was assessed by optical coherence tomography from baseline to week 24. Immunogenicity assessment was done in both arms at baseline, week 16 and week 24. Safety evaluation included clinical and ophthalmic examination, adverse events, vital signs, laboratory parameters and immunogenicity in both treatment arms. RESULTS: In the biosimilar test arm, 104 (98.11%) and 105 (99.06%) patients lost fewer than 15 letters in visual acuity at week 16 and week 24, respectively, compared with 53 (100%) at both follow-ups in reference arm. In the test arm, 27 (25.47%) and 34 (32.08%) patients gained at least 15 letters in visual acuity till week 16 and week 24 respectively, compared with 17 (32.08%) and 23 (43.30%) in the reference arm. In the test arm, mean change in central macular thickness at 24 weeks was -89.93 µm against -64.42 µm in the reference arm. Difference was statistically not significant for any endpoint at 16 and 24 weeks for the primary and secondary endpoints. CONCLUSION: The evaluation of efficacy, safety and immunogenicity was concluded to show no meaningful clinical difference for biosimilar ranibizumab with the reference product.
ABSTRACT
PURPOSE OF STUDY: Omalizumab the first anti-IgE antibody is proven with several real-world studies and meta-analyses as important adjuvant in severe allergic asthma. This study was undertaken for the first omalizumab biosimilar to establish clinical biosimilarity and interchangeability with originator product. MATERIALS AND METHODS: In this randomized, double-blind comparative study 105 subjects (70 subjects in the study group and 35 subjects in the reference group) were dosed up to week 16 as double blind phase and responders entered open label phase till week 24. All responders at week 16 received study product in open-label phase of the study as per their dosing schedule till week 24. The additional efficacy assessment visit was performed till week 24. Safety follow up visit was performed in responders at week 26. The pharmacokinetic (PK) and pharmacodynamic (PD) assessment was planned in 48 subjects after first dose of omalizumab. RESULTS: In double blind phase, 4 (5.80%) asthma exacerbations were reported in study arm compared to 1 (2.86%) asthma exacerbation in reference arm with no statistically significant difference (p>0.05). The time to first asthma exacerbation was 53 days in study arm compared to 62 days in reference arm. In study and reference arm, the mean change from baseline in forced expiratory volume in one second (FEV1%) was 7.51 and 5.98 at week 4; and 12.30 and 8.94 at week 16 respectively while mean change from baseline in forced expiratory volume in one second/forced vital capacity (FEV1/FVC%) was 4.20 and 4.06 at week 4 and 6.77 and 7.10 at week 16 respectively (no statistically significant difference, p>0.05). At week 16, 4 (5.80%) subjects in study arm had 50-75% inhaled corticosteroids (ICS) dose reduction compared to 2 (5.71%) subjects in reference arm. The proportion of subjects with meaningful improvement in Asthma Quality of Life Questionnaire (AQLQ) (improvement in overall AQLQ score ≥0.5), mean change in overall Asthma Control Questionnaire (ACQ) score and proportion of responders based on Global evaluation of treatment effectiveness (GETE) assessment also was similar at 16 weeks. A total of 101 adverse events were reported out of which 63 were reported in the study or biosimilar arm and 38 were reported in the reference or innovator arm. Two serious adverse events (SAEs) were reported, one in each arm. No deaths occurred during this study and the safety observations are consistent with the known safety profile of omalizumab. All the samples analysed in this study were negative for anti-omalizumab antibodies. There was no significant difference in the PK and PD evaluation. CONCLUSION: The evaluation of pharmacokinetics, pharmacodynamics, efficacy, safety and immunogenicity was concluded to show no meaningful clinical difference of the biosimilar omalizumab with the reference product.
