Data from the phase 3 Mandala trial shows that a fixed dose of albuterol and budesonide when met its primary endpoint by demonstrating statistically significant and clinically meaningful reductions in the risk of severe exacerbations compared to albuterol, when used as a rescue medicine.

“This represents a paradigm shift in the treatment of asthma. We see this combination treatment, which is the first of its kind, as becoming part of standard therapy,” said author Reynold Panettieri Jr., a professor of medicine at Rutgers Robert Wood Johnson Medical School and vice-chancellor of Clinical and Translational Science.

The study included more than 3,000 asthma patients from 295 sites throughout the U.S., Europe, and South America, and was designed to evaluate the safety and efficacy of a combination of albuterol and budesonide as a treatment for patients with modest to severe asthma. Albuterol is a short-acting beta 2-agonist that works by attaching to minuscule proteins called beta receptors in the airways, relaxing the muscles there. Budesonide is a corticosteroid that decreases swelling and irritation in the airways. The trial was divided into three groups. With many patients already on daily maintenance asthma therapy, participants in the groups were given one of three different rescue therapies to use in the event of an exacerbation. The groups included a combination of albuterol and a high dose of budesonide. albuterol and a lower dose of budesonide, ad a control group who was given just albuterol.

Scientists found that albuterol with a higher dose of budesonide reduced the risk of an asthma attack by 27 percent in the short term and 24 percent annually. This combination also reduced the use of corticosteroids by 33 percent.

“With this new inhaler that delivers more inhaled steroids every time patients take the rescue therapy, they’re getting more at a time when they’re having a flare-up and when they need it,” said Panettieri. “We showed that, beyond decreasing their exacerbations, it decreased their need for oral steroids after a flare-up.”

In another phase 3 study, the DENALI trial, this combination therapy met dual primary endpoints, with the candidate showing a statistically significant improvement in lung function measured by forced expiratory volume in one second (“FEV1”) compared to albuterol and budesonide, individually, and compared to placebo. These full data have yet to be published.

The complete trial may be read here.

Other authors of the study included Alberto Papi of the University of Ferrara, Italy; Bradley Chipps of Capital Allergy & Respiratory Disease, Calif.; Frank Albers, Allison Jeynes-Ellis and Robert Rees of Avillion LLP; Richard Beasley of the Medical Research Institute of New Zealand; Christy Cappelletti, Mark Cooper and Eva Johnsson of AstraZeneca PLC; Lynn Dunsire of Contrast Consultancy Ltd., U.K.; and Elliot Israel of Brigham and Women’s Hospital, Harvard Medical School.