Tezepelumab improves patient-reported outcomes in patients with severe, uncontrolled asthma in PATHWAY

Corren, Jonathan; Gil, Esther Garcia; Griffiths, José-Marie; Parnes, Jane R.; Merwe, René van der; Sałapa, Kinga; O’Quinn, Sean

doi:10.1016/j.anai.2020.10.008

Cited by 41 publications

(40 citation statements)

References 32 publications

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“…These findings suggest that administration of tezepelumab by patients or caregivers was sufficient to achieve improvements in ACQ-6 comparable to those observed in the phase 2b PATHWAY study, during which tezepelumab was administered by an HCP in the clinic. 19 Tezepelumab PK were consistent between devices and were comparable with the findings from previous clinical studies, including PATHWAY, 2 PATH-BRIDGE 10 and an additional phase 1 study in healthy individuals. 20 Together with the comparable improvements in asthma control observed in the present study and in the PATHWAY study with tezepelumab treatment, these data indicate that exposure to tezepelumab after at-home selfadministration using an APFS or AI is sufficient to obtain the clinical benefit observed in the PATHWAY study.…”

Section: Dovepresssupporting

confidence: 87%

Functionality and Performance of an Accessorized Pre-Filled Syringe and an Autoinjector for At-Home Administration of Tezepelumab in Patients with Severe, Uncontrolled Asthma

Alpizar¹,

Megally²,

Chen³

et al. 2021

JAA

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Background:Tezepelumab is an anti-thymic stromal lymphopoietin monoclonal antibody in development for the treatment of severe asthma. This study assessed the functionality and performance of an accessorized pre-filled syringe (APFS) and an autoinjector (AI) for administration of tezepelumab in the clinic and at home. Methods: This phase 3, multicenter, randomized, open-label, parallel-group study (PATH-HOME, ClinicalTrials.gov identifier: NCT03968978) was conducted in patients aged 12-80 years with asthma that was uncontrolled despite treatment with medium-to high-dose inhaled corticosteroids plus at least one additional controller medication. Patients received six subcutaneous doses of tezepelumab 210 mg via APFS or AI. The first dose was administered by a healthcare professional, and patients or caregivers administered subsequent doses. First, second, third and final doses were administered in the clinic; fourth and fifth doses were administered at home. The primary endpoint was the proportion of successful administrations of tezepelumab. Secondary endpoints included the functionality and performance of the devices, Asthma Control Questionnaire (ACQ)-6 score, pharmacokinetics and safety. Results: Overall, 216 patients were randomized (APFS, n=111; AI, n=105). Tezepelumab was successfully administered via APFS by 91.7% of the participants (100/109) and via AI by 92.4% (97/105). Overall, 95.4-97.1% of at-home administrations were successful across device groups. Malfunction occurred in 6 of 655 dispensed APFSs and 5 of 624 dispensed AIs. Clinically meaningful improvements in ACQ-6 score were observed after 24 weeks in 81.1% and 76.2% of the patients in the APFS and AI groups, respectively. Tezepelumab pharmacokinetics were consistent between device groups and with previous studies. The most common adverse event was nasopharyngitis (9.3%). Injection-site reactions occurred in 5.7% and 0% of the patients in the AI and APFS groups, respectively. Conclusion:This study demonstrated that the APFS and AI were functional and reliable, and performed equally well at home and in the clinic.

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Section: Dovepresssupporting

confidence: 87%

Functionality and Performance of an Accessorized Pre-Filled Syringe and an Autoinjector for At-Home Administration of Tezepelumab in Patients with Severe, Uncontrolled Asthma

Alpizar¹,

Megally²,

Chen³

et al. 2021

JAA

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“…These cytokines have therefore been studied as useful targets for BA. Indeed, tezepelumab, a fully human anti-TSLP monoclonal antibody, has been shown to improve asthma control and FEV1 and reduce exacerbations, blood eosinophyl count, FENO and total serum IgE in phase II trials [83,84]. An anti-IL-33 monocloclonal antibody, REGN3500, has been shown to prevent airway remodeling in a murine model of house dust-mite-induced asthma and to reduce eosinophyls infiltration and airway hyperreactivity in an ovalbumin induced asthma murine model [85][86][87].…”

Section: Monoclonal Antibodies Targeting Type 2 Inflammationmentioning

confidence: 99%

Strategies Targeting Type 2 Inflammation: From Monoclonal Antibodies to JAK-Inhibitors

et al. 2021

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Bronchial asthma and its frequent comorbidity chronic rhinosinusitis (CRS), are characterized by an inflammatory process at lower and upper respiratory tract, with a variability in terms of clinical presentations (phenotypes) and distinct underpin pathophysiological mechanisms (endotypes). Based on the characteristics of inflammation, bronchial asthma can be distinguished into type 2 (eosinophilic) or nontype 2 (noneosinophilic) endotypes. In type 2 asthma endotype, the pathogenic mechanism is sustained by an inflammatory process driven by Th2 cells, type 2 innate lymphoid cells (ILC2) and type 2 cytokines, which include interleukin (IL)-4, IL-5, IL-9 and IL-13. The definition of asthma and chronic rhinusinusitis phenotype/endotype is crucial, taking into account the availability of novel biologic agents, such as monoclonal antibodies targeting the classical type 2 cytokines. Recently, new therapeutic strategies have been proposed and analyzed in preliminary clinical trials. Among them Janus kinase (JAK) inhibitors, now largely used for the treatment of other chronic inflammatory diseases such as rheumatoid arthritis and inflammatory bowel diseases, is receiving great relevance. The rationale of this strategy derives from the data that JAK is a tyrosine kinase involved in the signaling of T cell receptor and of several cytokines that play a role in allergic respiratory disease, such as IL-2, IL-4 and IL-9. In this review, we discuss whether treatment with biological agents and JAK inhibitors may be equally effective in controlling type 2 inflammatory process in both asthma and CRS.

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“…As illustrated in Figure 1, mepolizumab, benralizumab, and reslizumab all target IL-5, while dupilumab inhibits IL-4Rα, the shared receptor of IL-4 and IL-13. The anti-IL-33 mAb, REGN3500, has completed phase II testing (15), and phase III trials for tezepelumab, an anti-TSLP ILC2 activation-inhibiting mAb, are underway (23) following promising phase II results (24).…”

Section: Airwaymentioning

confidence: 99%

Therapeutic manipulation of innate lymphoid cells

Cobb¹,

Verneris²

2021

JCI Insight

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Since their relatively recent discovery, innate lymphoid cells (ILCs) have been shown to be tissue-resident lymphocytes that are critical mediators of tissue homeostasis, regeneration, and pathogen response. However, ILC dysregulation contributes to a diverse spectrum of human diseases, spanning virtually every organ system. ILCs rapidly respond to environmental cues by altering their own phenotype and function as well as influencing the behavior of other local tissue-resident cells. With a growing understanding of ILC biology, investigators continue to elucidate mechanisms that expand our ability to phenotype, isolate, target, and expand ILCs ex vivo. With mounting preclinical data and clinical correlates, the role of ILCs in both disease pathogenesis and resolution is evident, justifying ILC manipulation for clinical benefit. This Review will highlight areas of ongoing translational research and critical questions for future study that will enable us to harness the full therapeutic potential of these captivating cells.

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Tezepelumab improves patient-reported outcomes in patients with severe, uncontrolled asthma in PATHWAY

Cited by 41 publications

References 32 publications

Functionality and Performance of an Accessorized Pre-Filled Syringe and an Autoinjector for At-Home Administration of Tezepelumab in Patients with Severe, Uncontrolled Asthma

Functionality and Performance of an Accessorized Pre-Filled Syringe and an Autoinjector for At-Home Administration of Tezepelumab in Patients with Severe, Uncontrolled Asthma

Strategies Targeting Type 2 Inflammation: From Monoclonal Antibodies to JAK-Inhibitors

Therapeutic manipulation of innate lymphoid cells

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