Featured Research

from universities, journals, and other organizations

Monoclonal antibody appears effective and safe in asthma phase IIa trial

Date:
May 21, 2013
Source:
American Thoracic Society (ATS)
Summary:
A novel approach to obstructing the runaway inflammatory response implicated in some types of asthma has shown promise in a Phase IIa clinical trial, according to U. S. researchers.

A novel approach to obstructing the runaway inflammatory response implicated in some types of asthma has shown promise in a Phase IIa clinical trial, according to U. S. researchers.

Their research will be presented at the American Thoracic Society 2013 International Conference and published simultaneously online in the New England Journal of Medicine.

The randomized, double-blind, placebo-controlled trial tested the efficacy and safety of the monoclonal antibody, dupilumab, in patients with "persistent, moderate-to-severe asthma" and elevated eosinophils, which are immune cells that mobilize in response to allergens and infections and are commonly seen in asthma.

According to lead author Sally Wenzel, MD, director of the University of Pittsburgh Asthma Institute, the combination of inhaled glucocorticosteroids (ICS) and long-acting beta agonists (LABA), which is a cornerstone of asthma controller therapy, does not work sufficiently in 10 to 20 percent of asthma patients in the United States.

"Asthma that is difficult to treat is increasingly recognized as comprising different phenotypes," she said. "With this study, we wanted to see whether dupilumab would reduce a surrogate index for asthma exacerbations when given with ICS and LABA and when those two therapies were withdrawn."

Dupilumab, a fully human monoclonal antibody discovered by Regeneron Pharmaceuticals and being developed by Regeneron and Sanofi, thwarts activation of the Th2 immune response implicated in asthma by blocking two cytokines, interleukin-4 and interleukin-13.

Over the course of a 12-week blinded treatment period and an 8-week follow-up, those patients who had received weekly injections of dupilumab experienced an 87 percent reduction in protocol defined asthma exacerbations, the primary endpoint of the study, vs. weekly placebo injections (odds ratio [95% CI]=0.08 [0.021 to 0.28]; p<0.01). Significant improvements were also reported for other relevant asthma outcomes such as lung function as assessed by forced expiratory volume in one second (FEV1) and morning peak expiratory flow, asthma symptoms and control, as well as, asthma reliever medication use. Many of these improvements were seen when dupilumab was added to ICS/LABA, with efficacy maintained despite background therapy withdrawal.

"Intriguingly," noted Dr. Wenzel, "dupilumab showed substantial efficacy in objective and patient-reported endpoints when added to ICS and LABA and when those therapies were discontinued."

Patients in the study received dupilumab or placebo added to their regular, twice daily dose of fluticasone/salmeterol. At Week 4, patients were instructed to withdraw the LABA (salmeterol). Between Weeks 6 and 9, they tapered off fluticasone, the ICS.

A total of 104 patients, aged 18 to 65, participated in the study. Half received the monoclonal antibody; half received placebo. All had persistent, moderate-to-severe asthma that was not well-controlled by medium to high doses of combined ICS and LABA therapy. The patients also had elevated blood (≥ 300 cells/l) or sputum (≥3%) eosinophils at screening.

The study found no clear change in blood eosinophils with dupilumab therapy; however, other biomarkers decreased, including fractional exhaled nitric oxide, thymus and activation regulated chemokine, immunoglobulin E and eotaxin-3, confirming the biologic activity of dupilumab.

Side effects occurring more frequently in the patients receiving the monoclonal antibody vs. placebo included injection site reactions, nasopharyngitis, nausea and headache, but were not considered severe.

According to Dr. Wenzel, the current study, exhibited a "magnitude and breadth" of efficacy that exceeded other studies of cytokine inhibition in asthma. She and her investigator colleagues speculate that the stronger outcome came as a result of blocking two cytokines, IL-4 and IL-13, rather than a single one.

They called for further studies to confirm these observations and better define the target population, dosing regimen, and long-term efficacy and safety

The trial was sponsored by Sanofi and Regeneron.


Story Source:

The above story is based on materials provided by American Thoracic Society (ATS). Note: Materials may be edited for content and length.


Journal Reference:

  1. Sally Wenzel, Linda Ford, David Pearlman, Sheldon Spector, Lawrence Sher, Franck Skobieranda, Lin Wang, Stephane Kirkesseli, Ross Rocklin, Brian Bock, Jennifer Hamilton, Jeffrey E. Ming, Allen Radin, Neil Stahl, George D. Yancopoulos, Neil Graham, Gianluca Pirozzi. Dupilumab in Persistent Asthma with Elevated Eosinophil Levels. New England Journal of Medicine, 2013; 130521051515005 DOI: 10.1056/NEJMoa1304048

Cite This Page:

American Thoracic Society (ATS). "Monoclonal antibody appears effective and safe in asthma phase IIa trial." ScienceDaily. ScienceDaily, 21 May 2013. <www.sciencedaily.com/releases/2013/05/130521105216.htm>.
American Thoracic Society (ATS). (2013, May 21). Monoclonal antibody appears effective and safe in asthma phase IIa trial. ScienceDaily. Retrieved July 26, 2014 from www.sciencedaily.com/releases/2013/05/130521105216.htm
American Thoracic Society (ATS). "Monoclonal antibody appears effective and safe in asthma phase IIa trial." ScienceDaily. www.sciencedaily.com/releases/2013/05/130521105216.htm (accessed July 26, 2014).

Share This




More Health & Medicine News

Saturday, July 26, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

AFP (July 24, 2014) A so-called drugs rehab 'clinic' is closed down in Pakistan after police find scores of ‘patients’ chained up alleging serial abuse. Duration 03:05 Video provided by AFP
Powered by NewsLook.com
Too Few Teens Receiving HPV Vaccination, CDC Says

Too Few Teens Receiving HPV Vaccination, CDC Says

Newsy (July 24, 2014) The Centers for Disease Control and Prevention is blaming doctors for the low number of children being vaccinated for HPV. Video provided by Newsy
Powered by NewsLook.com
New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins