Severe asthma, the first broad-spectrum drug arrives
When medications fail to control asthma, patients are debilitated by constant flare-ups of symptoms and limitations in lung capacity. A situation that leads them to have a greater risk of mortality and compared to patients with persistent asthma they have double the risk of hospitalizations. For these patients, which are estimated to number around 300,000 in Italy, there is now an additional therapeutic opportunity, tezepelumab. It is a monoclonal antibody, the first of a new class of biological drugs capable of acting at the epithelial barrier level in order to block the action of a key inflammatory substance in the development of the disease. The new drug is indicated as adjunctive maintenance therapy in patients aged 12 years and older with the disease and who are not adequately controlled despite the use of high-dose inhaled corticosteroids, in addition to another drug to treat maintenance.
“Severe asthma is related to an important unmet clinical need and is also severely under-diagnosed. With a view to better management of the disease, the advent of biological drugs has not only brought about a change in perspectives in understanding the mechanisms of the disease but has brought transversal benefits, significantly improving the impact of the disease on the quality of life of patients” , comments Giorgio Walter Canonica, Professor & Senior Consultant Center for Personalized Medicine Asthma and Allergies Humanitas University & Clinical and Research Institute IRCCS Milan. “The approval of tezepelumab not only responds to an important unmet clinical need, but represents a further step forward for the treatment of severe asthma which will allow us to aim towards an increasingly effective personalization of therapy and expand therapeutic options for respond to the specific needs of patients affected by the disease”.
The specific action of tezepelumab
Today, patients with severe asthma take a combination of inhaled molecules as background therapy, with the possibility of adding monoclonal antibodies for eligible patients. In particular, patients with severe allergic asthma or severe eosinophilic asthma have biological options available that aim to block individual elements of the complex immune-inflammatory cascade responsible for the symptoms and clinical manifestations of asthma. “These treatments leave some mediators active that can still cause flare-ups and compromise disease control. They may not be suitable for patients with multiple inflammatory pathways involved in asthma, and therefore may not respond to the heterogeneity of the disease and its potential variability over time”, – states Paola Rogliani, Professor of Respiratory Diseases, University of Rome Tor Vergata; Director of the Respiratory Diseases Unit, Fondazione Policlinico Tor Vergata –. “Tezepelumab acts directly on epithelial damage and therefore on the signal triggering the inflammatory cascade, allowing the simultaneous modulation of various inflammatory mediators involved in asthma. It responds to the clinical need of severe forms of asthma induced by various inflammatory triggers and exacerbations, which until now did not have such a therapeutic option available.”
Evidence of efficacy
The approval of the Italian Medicines Agency is based on the positive results of the Phase IIb PATHWAY Study and the Phase III NAVIGATOR Study which showed the efficacy of tezepelumab in terms of reduction of disease exacerbations, improvement of lung function, control of disease symptoms and quality of life both in patients with expression of inflammatory biomarkers such as blood eosinophils, FeNO and serum IgE, and in patients with low or absent expression of these markers. The long-term safety and efficacy of tezepelumab were confirmed in the DESTINATION two-year extension study. Clinical studies have highlighted its effectiveness on 2 thousand patients with a clinically significant reduction in exacerbations, from 50 to over 80%.
“Tezepelumab is today the only biological drug available capable of acting at the epithelial barrier level, inhibiting the binding between thymic stromal lymphopoietin (TSLP) and its receptor localized on multiple cellular elements involved in the inflammatory and bronchoconstrictive response of asthma. The target of tezepelumab, TSLP, is a key pro-inflammatory cytokine released predominantly by bronchial epithelial cells following airway damage induced by various exogenous stimuli (viruses, bacteria, allergens, smoking, mechanical stress and pollutants) and plays an important role in the pathogenesis of asthma”, comments Matteo Bonini, Full Professor of Respiratory Diseases at the Sapienza University of Rome. “Thanks to the specific mechanism of inhibition of TSLP, tezepelumab is able to express a pleiotropic pharmacological action, directed towards multiple cellular elements involved in the pathophysiology of asthma and related clinical manifestations.
A complex pathology
The onset of severe asthma can depend on various factors, and it is therefore difficult to identify a management that is suitable for all patients and the best therapeutic path for each individual patient. “This is why we are very happy with the approval of a new therapeutic option capable of responding to a significant unmet need and which allows people who today have a diagnosis of severe asthma, but are not eligible for treatment, to be able to have access to a new effective and safe treatment capable of better controlling the pathology and improving the quality of life”, declares Simona Barbaglia, President of the National Association of Patients Let’s Breathe Together APS -. “Come Breathe Together we have been committed since 2018 to the recognition of severe asthma as a distinct disabling pathology and therefore to the assignment of an exemption code other than asthma, which includes a wider range of free diagnostic and therapeutic services, in addition to the guarantee of social protection that is currently not commensurate with the severity of the disease”.
