March 4 An experimental drug reduced asthma attacks in patients with severe uncontrolled asthma by 60 percent and helped improve lung function in certain patients, indicating that the drug could offer the first personalized approach to treatment, according to data from a clinical trial released on Tuesday.
The biotech drug lebrikizumab, which was developed by Roche Holding's Genentech unit, was tested at three doses in patients whose asthma was not sufficiently controlled even with high-dose, inhaled corticosteroids and a second asthma-controlling therapy.
In the 463-patient Phase IIb study, lebrikizumab reduced asthma attacks by a statistically significant 60 percent more than a placebo in patients found to have a high level of the protein periostin, according to pooled data from the three doses tested - 37.5 milligrams, 125 mg and 250 mg. That compared with a 5 percent reduction versus placebo over 28 to 52 weeks of treatment in those with low levels of periostin.
"If this drug gets approved we would have for the first time a personalized approach other than just blanket therapy for everyone with uncontrolled disease," Dr Nicola Hanania, one of the study's lead investigators, said in a telephone interview.
Lebrikizumab works by blocking interleukin-13, or IL-13, which contributes to airway inflammation and mucous production. Periostin is believed to be a biomarker for IL-13 activity and a likely predictor of how well the Roche drug will work.
Roche is also developing a blood test for periostin in order to identify the patients most likely to benefit from lebrikizumab, which is injected once every four weeks.
Hanania, who is director of the Asthma Clinical Research Center at Baylor College of Medicine in Houston, called the data from the study "very exciting."
In those with severe asthma receiving existing treatments, "we still see patients who still have symptoms, who still have exacerbations, hospital admissions, and this is the type of patient this study was targeting," he said.
Curiously, the greatest level of asthma attack reduction, at 81 percent, was seen with the lowest dose of lebrikizumab, something that Hanania called surprising. Hanania, who presented the data at the American Academy of Allergy, Asthma and Immunology (AAAAI) meeting in San Diego, noted, "Higher is not always the better."
Fifteen percent of the estimated 25 million Americans with asthma suffer from severe asthma, according to the National Institutes of Health. About half of severe asthmatics are believed to have high periostin levels.
Among patients with high level periostin, the drug improved lung function by 9.1 percent after 12 weeks, compared with an improvement of just 2.6 percent in the low periostin group.
Lung function was tested by change in FEV1, a measure of the maximum amount of air that can be forcibly exhaled in one second. The greatest improvement in FEV1, of 10.7 percent, was seen with the 125 mg dose of lebrikizumab.
"Statistically it's significant, and I believe it is clinically significant because it goes hand in hand with reduction in exacerbations," Hanania said of the lung function improvement seen in the high periostin group.
The incidence of serious adverse side effects was low and similar in the lebrikizumab and placebo arms of the study, researchers said.
"The safety profile was very reassuring. Nothing really stood out as major side effect or major serious adverse effect," Hanania said.
If the results are replicated in large, ongoing Phase III trials that will include more than 2,000 patients, Roche said it expects to seek approval for the drug in 2016.
"As a clinician, this is important because there is a great need for additional therapy for those with poorly controlled asthma," Hanania said. "It's a light at the end of the tunnel."