An NIH Trial of Severe Asthma Treatment Tailored to Subtypes

Although severe asthma accounts for only 3% to 10% of the adult population with asthma, it makes up more than half of healthcare expenses related to asthma. Some of that cost includes the development of new and effective treatments.

People with severe asthma have difficult-to-control symptoms and are prone to frequent asthma exacerbations. In addition, symptom triggers and response to treatment can vary based on the presence of biomarkers, such as immunoglobulin (IgE), eosinophils and neutrophils. Because of this variability severe asthma patients are grouped into various subtypes. Developing treatments that target specific pathology can be challenging.

The National Heart, Lung, and Blood Institute is funding a study designed to match individual severe asthma patients with treatments that specifically address the underlying pathology of their disease subtype. The Precision Interventions for Severe and/or Exacerbation-Prone Asthma Network (PrecISE) trial started in 2019 and is expected to be completed in June 2023. This trial is designed to use an adaptive design and precision medicine to match severe asthma subgroups with treatment arms that target the mechanisms of each asthma subtype. A primary objective of the study is to identify novel treatments for patients with severe asthma that are effective in their biomarker-based subgroup.

Trial interventions include clazakizumab, an interleukin-6 inhibitor, to target systemic inflammation that may worsen asthma. Gleevec (imatinib), a kinase inhibitor used as a cancer drug, that may be repurposed for asthma because it has been shown that it may reduce mast cells in the airways. Covosonstat helps increase levels of S-nitrosoglutathione (GSNO), which is an endogenous bronchodilator. A dietary supplement that affects energy breakdown and another that provides lyophilates of respiratory bacteria make up the last two arms of the study.

Each intervention will last four months, and researchers will be able to rapidly evaluate each group's response to treatment while simultaneously studying multiple interventions. The PrecISE trial is currently in phase 2. Treatments that prove to be effective in this phase could proceed to larger phase 3 trials.