In the pipeline: New therapies to manage severe therapy-resistant asthma

Pediatric Asthma - Girl blowing a dandelion

Over seven million children in the U.S. have been diagnosed with asthma. Many patients only experience mild, intermittent symptoms and can be treated symptomatically with medicines like Abluterol. Most of the remaining patients can achieve good asthma control by using daily medicines to decrease inflammation in the lung.

However, about 10 percent of children with asthma have difficult-to-treat disease. The challenge is identifying new therapies for these patients so they may live free of daily symptoms or the fear of exacerbations.

Defining the challengesAsthma statistics

Many children with persistent or difficult-to-treat asthma have trouble controlling symptoms. In some cases, this is due to not using prescribed medicines regularly or improper technique — leading to poor delivery of inhaled medicines to the lungs.

In contrast, severe therapy-resistant asthma (STRA) is characterized as difficult-to-treat despite management of these factors. These children have regular or daily symptoms such as waking up at night coughing and wheezing after moderate exercise. They also suffer from frequent exacerbations (a.k.a. “asthma attacks”) that can lead to hospitalizations. Repeated attacks may result in permanent loss of lung function. Therefore, new therapies are needed for these patients who don’t respond to standard therapy. 

Understanding true therapy-resistant asthma

In many cases, a home visit, focusing on environmental controls, is helpful and can decrease the need for hospitalization and emergency-department visits. However, a subset of patients with truly severe therapy-resistant asthma remain even after all these measures are taken. While true therapy-resistant asthma is rare, these patients consume a great deal of resources and have a significantly decreased quality of life.

The allergy/asthma connection

Approximately two-thirds of children with asthma have allergies. Therefore, targeting the allergic pathway is one approach. Omalizumab, sold under the trade name Xolair, has been approved for many years for teenagers and adults who have significant allergies as a trigger for their asthma. This medicine targets IgE, the antibody that causes allergies. Interestingly, omalizumab is very effective in preventing asthma exacerbations but is less effective in improving lung function. Recently, the FDA approved omalizumab for patients age 6-11 which gives us a new tool for severe asthma patients in this age group.

The power of personalized asthma therapy

As personalized therapy becomes more of a reality, pharmaceutical companies and asthma experts are subdividing asthma patients into different subgroups and individualizing therapy. Many patients with severe asthma have a specific type of white-blood cell called eosinophils in their lungs as well as the blood.

Research in mice suggests these eosinophils are a driving factor in ongoing asthma, at least in some patients. Several new therapies were then developed targeting eosinophils. An initial trial of one of these therapies, which included all patients with asthma, did not show any benefit. However, additional studies in which only patients with elevated eosinophil levels (in either the blood or lung) were performed and showed significant decrease in asthma exacerbations.

Defining new therapies

Mepolizumab is an attractive option for adolescents and adults with severe asthma due to elevated eosinophils who have failed standard therapy. Two new therapies have been approved for patients with elevated eosinophil levels, including mepolizumab (Nucala). which is approved for patients 12 and over. Rezlizumab (Cinqair), the second therapy, is only approved for adults (18 and over).

Unfortunately, this medicine is expensive and requires subcutaneous injections. While mepolizumab is not for everyone, it is an attractive option for adolescents and adults with severe asthma due to elevated eosinophils who have failed standard therapy.

Other new therapies are in development, including more potent IgE targeting molecules, and medicines that target other signaling pathways. While we are not there yet, the outlook is bright for patients with severe asthma.

Learn more about Boston Children’s Allergy and Asthma Program and the upcoming Pediatric Asthma & Allergy for Primary Care Providers CME.

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About the author: Andrew MacGinnitie, MD, PhD, is clinical director of Boston Children’s Division of Immunology and assistant professor of pediatrics at Harvard Medical School.