Severe asthma mAb approved in pre-filled single use pen for self-administration

22nd January 2023

Tezepelumab is a treatment for patients with severe asthma and has been approved in the EU as a pre-filled pen for self-administration

In a press release from the manufacturer, AstraZeneca, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has now approved a pre-filled pen containing tezepelumab, for self-administration to patients aged 12 years and older with severe asthma. The release adds that the CHMP opinion can actually be implemented without the need for a European Committee decision due to the nature of the type II label variation.

Tezepelumab is a first-in-class monoclonal antibody that specifically binds to thymic stromal lymphopoietin thereby stopping its interaction with the heterodimeric receptor. Thymic stromal lymphopoietin is an epithelial-derived cytokine with an important role in both the initiation and persistence of airway inflammation in asthma. When used as an add-on treatment for patients with severe, uncontrolled asthma, tezepelumab has been shown to be both safe and effective. Data for the drug in patients with severe asthma has shown that it leads to fewer disease exacerbations, improved lung function, asthma control and health-related quality of life compared with placebo.

Tezepelumab (brand name Tezspire) will be available as a fixed-dose 210mg subcutaneous injection via a pre-filled, single use auto-injector but also as single-use syringe with both forms designed to be given every four weeks. The pre-filled pen enables both patients and carers to self-administer the treatment at home.

Tezepelumab pre-filled pen efficacy

Data on the use of the pre-filled pen comes from a study which showed that in 315 adults, the pre-filled syringe provided similar pharmacokinetic parameters when compared to a single subcutaneous dose. In addition, a second study showed that use of the pre-filled syringe and an auto-injector gave rise to similar and clinically meaningful improvements in the asthma control questionnaire-6 score after 24 weeks.

In the press release, Professor Ian Pavord, Professor of Respiratory Medicine at the University of Oxford and Honorary Consultant Physician at the Oxford University Hospitals, said: ‘Severe asthma continues to have a debilitating impact for people living with the disease. I believe the approval of the Tezspire pre-filled pen will be welcome news for physicians and patients in Europe as it offers increased choice and greater flexibility when administering this important medicine.’

AstraZeneca has also submitted data to the US Food and Drug Administration for approval of the pre-filled pen.

Biologic add-on therapy effective for severe asthma in real-world study

19th January 2023

Dupilumab add-on therapy in severe asthma improves the exacerbation rate and disease control according to the findings of a real-world study

Dupilumab add-on treatment in patients with severe asthma is associated with significant improvements in the exacerbation rate, asthma control, pulmonary function and quality of life, according to the findings of a real-world study by Dutch researchers.

Severe asthma occurs when adequate control cannot be achieved by high-dose treatment with inhaled corticosteroids and additional agents (i.e., long-acting inhaled beta 2 agonists, montelukast, and/or theophylline) or by oral corticosteroid treatment, for at least six months per year. Although it is generally considered that 5% and 10% of all asthmatic patients have severe disease, a 2015 Dutch study of asthmatic adults, found that only 3.6% qualified for a diagnosis of severe refractory asthma, representing 10.4 patients per 10,000 inhabitants. There are currently several biological agents used to treat severe asthma including mepolizumab, benralizumab and dupilumab, with the latter agent binding to the interleukin-4-receptor-α and therefore targeting interleukin-4 and interleukin-13, both of which are key cytokines in type-2 (T2) inflammation. Moreover, the prevalence of type 2 asthma in severe, uncontrolled disease has been found to be present in the majority (89%) of cases. Dupilumab add-on therapy is therefore an appropriate treatment option in severe asthma and effective, as shown in randomised, controlled trials. Nevertheless, while effective in clinical trials, some evidence has shown, especially with mepolizumab, that a large proportion of real-world mepolizumab-treated population with severe asthma, would be excluded from the clinical trial population, raising concerns over the generalisability of trial findings.

In the present study, the Dutch team set out to assess the efficacy and safety of dupilumab add-on therapy for severe asthma in a real-world cohort. The team retrospectively examined the impact of subcutaneously administered dupilumab, either at hospital or by self-administration at home, at a dose of 200 mg every 14 days, or 300 mg in patients with other type 2 co-morbidities. The primary endpoint was the annually exacerbation-rate (AER), whereas secondary outcomes included asthma control, pulmonary function and quality of life and the changes were assessed by comparing baseline to 12 month values.

Dupilumab add-on therapy and asthma outcomes

A total of 148 patients with a median age of 52.5 years (57% male) were included in the study, of whom 73% had allergic asthma (which includes the type 2 form).

The AER reduced from 3.00 at baseline to 1.00 at 12 months with dupilumab use (p < 0.001). In fact, after 12 months of treatment, 46% of dupilumab add-on therapy patients remained completely exacerbation-free. Similarly, asthma-controlled-questionnaire-5 scores reduced over time, from a median of 3.00 at baseline to 1.40 after 12 months of dupilumab use (p < 0.001). Furthermore, lung function (based on FEV1) also improved, increasing from a median of 2.21 at baseline to 2.51 at 12 months (p < 0.001) in the dupilumab group.

The authors concluded that dupilumab add-on therapy in severe asthma was associated with significant improvements in the exacerbation rate, asthma control and pulmonary function, which was in line with findings observed in previous Phase III trials.

Citation
Thelen JC et al. Efficacy and safety of dupilumab as add-on therapy for patients with severe asthma: A real-world Dutch cohort study. Respir Med 2023

Risankizumab not beneficial in patients with severe asthma

4th November 2021

Risankizumab use in patients with severe asthma is of no benefit and was found to shorten the time to asthma worsening compared with placebo.

Use of risankizumab in patients with severe asthma led to a reduction in the time to worsening compared to placebo. This was the finding of a randomised trial of the drug by a team from the Institute for Lung Health, Department of Respiratory Sciences, University of Leicester, Leicester, UK. Asthma is due to inflammation and a narrowing of the airways and this leads to the major symptoms of cough, wheeze, chest tightness and a shortness of breath. In 2019, asthma was estimated to affect 262 million people and caused 461000 deaths. The prevalence of severe asthma has been estimated from a Dutch study to be 3.6% or 10.4 patients per 10,000.

The cytokine, interleukin-23 (IL-23) produced by T-helper 17 cells, has been implicated in the development of allergic asthma and in fact, serum IL-23 levels have been found to elevated in asthmatic children and therefore could be used as a marker of bronchial function impairment. Risankizumab binds to and inhibits IL-23 and this action has proved to be of value in psoriasis and Crohn’s disease and could therefore benefit patients with severe asthma although there is a lack of data in support of this view.

For the present study, the Leicester researchers conducted a phase 2a, randomised, double-blind trial to assess the efficacy and safety of risankizumab in adults with severe, persistent asthma. Patients aged 18 to 75 years and who were currently using medium to high-dose inhaled glucocorticoids with at least one additional controller medications and had a history of one or two severe asthma exacerbations in the previous 12 months, were included in the study. Individuals were randomised 1:1 to receive either 90 mg risankizumab or placebo, subcutaneously, once every 4 weeks for a total of 24 weeks. The primary endpoint was the time to the first asthma worsening, which was defined in several different ways, including a deterioration from baseline on 2 or more consecutive days or an 50% increase in the number of rescue medication puffs in a 24 hour period.

Findings

A total of 213 patients were analysed, 105 with a mean age of 54 years (65.7% female) given risankizumab. The median time to the first asthma worsening was 40 days in the risankizumab group and 86 days in the placebo arm (hazard ratio, HR = 1.46, 95% CI 1.05 – 2.04, p = 0.03). In addition, the hazard ratio for the time to the first severe exacerbation was 1.18 (95% CI 0.76 – 1.83) and hence not significantly different to placebo.

The researchers also examined sputum gene expression and found that in patients using risankizumab, there was down-regulation of genes associated with IL-23 at the end of the treatment period but this effect was absent at week 20, suggesting that attenuation of IL-23 signally was not consistent throughout the study.

The authors concluded that risankizumab was not beneficial for severe asthma and that it was actually worse than placebo. The suggested that their data challenged the view that targeting IL-23 was of value in the treatment of asthma.

Citation

Brightling CE et al. Risankizumab in Severe Asthma — A Phase 2a, Placebo-Controlled Trial. New Eng J Med 2021