A clinical trial involving more than 1,200 participants at 374 sites in 17 countries has
found that a new drug called benralizumab has the potential to safely improve
outcomes for people with severe asthma.
The study, called SIROCCO, is published in the Sept. 5
issue of The Lancet Respiratory Medicine.
“Our results showed that benralizumab significantly
reduced exacerbations and improved lung function with an acceptable safety
profile for patients with severe uncontrolled asthma with eosinophilia,” said the
study’s lead author, Eugene R. Bleecker, M.D., director of the Center for
Genomics and Personalized Medicine Research at Wake Forest Baptist Medical
According to the Centers for Disease Control and
Prevention, asthma affects approximately 25 million people in the United States,
with approximately 10 percent having severe or uncontrolled cases of the
respiratory disease. Eosinophilia – an elevated level of white blood cells
called eosinophils that causes inflammation and hyper-sensitivity in airways --
is present in approximately half of all asthma patients. The condition is associated
with increased asthma severity, greater frequency of exacerbations (episodes of
progressively worsening symptoms such as shortness of breath and wheezing) and
decreased lung function.
Patients with severe asthma rely on high-dosage inhaled corticosteroids
in combination with long-acting beta-agonists to control their disease. But
this therapy is not effective in all asthmatics, leaving many with uncontrolled
and ever-worsening cases, and can produce serious side-effects with frequent
Benralizumab is an antibody compound produced from a
single “parent” cell developed by Medimmune, a U.S. subsidiary of the
London-based pharmaceutical company AstraZeneca, to be a complimentary therapy
for adults and adolescents with severe asthma.
To test the safety and efficacy of the medication, the
researchers enlisted asthma patients ages 12 to 75 who had experienced two or
more exacerbations in the previous year while taking corticosteroids and
beta-agonists. The participants were randomly placed in three equal-sized groups
to receive over a 48-week period 30 mg of benralizumab every four weeks, 30 mg
every four weeks for the first three doses then the same dosage every eight
weeks, or a placebo. Approximately two-thirds of the participants in each group
had elevated eosinophil levels.
The study found that benralizumab decreased the annual exacerbation
rate by as much as 51 percent relative to placebo while reducing symptoms and
improving lung function in those
participants with severe, uncontrolled asthma with eosinophilia. The drug also
resulted in direct, rapid and nearly complete depletion of eosinophils at four
weeks, the first sampling point. Overall, the every-eight-weeks dosage schedule
proved either as or more effective than the every-four-weeks regimen.
indicate that the clinical benefit obtained from benralizumab translates into
better asthma control and improved quality of life,” Bleecker said, noting that
the results were consistent with those from a similarly designed 56-week clinical
trial of benralizumab called CALIMA.
Both phase 3 trials were funded by AstraZeneca and the
Japanese pharmaceutical and biotechnology company Kyowa Hakko Kirin.
Co-authors of the SIROCCO study are Mark FitzGerald,
M.D., University of British Columbia Institute for Heart and Lung Health (Canada);
Pascal Chanez, M.D., Aix Marseille University (France); Alberto Papi, M.D., University
of Ferrara (Italy); Steven F. Weinstein, M.D., Allergy & Asthma Specialists
Medical Group, Huntingdon Beach, Calif.; Peter Barker, Ph.D., Stephanie Sproul,
M.Math., Mitchell Goldman, M.D., AstraZeneca, Gaithersburg, Md.; Geoffrey
Gilmartin, M.D., Astra Zeneca, Cambridge, Mass.; Magnus Aurivillius, M.D., and
Viktoria Werkstrom, M.D., Astra Zeneca, Gothenburg, Sweden.
Disclosure: Bleecker serves as a consultant for AstraZeneca.