Featured Research

from universities, journals, and other organizations

Ataluren Phase 3 trial results in nonsense mutation cystic fibrosis

Date:
May 16, 2014
Source:
University Hospitals Case Medical Center
Summary:
The results of a Phase 3 study of ataluren in patients with nonsense mutation cystic fibrosis have been published, demonstrating positive trends in both the primary endpoint, lung function as measured by relative change in percent predicted FEV1 (forced expiratory volume in one second) and in the secondary outcome measure, rate of pulmonary exacerbations.

PTC Therapeutics, Inc. (NASDAQ: PTCT) today announced that the results of a Phase 3 study of ataluren in patients with nonsense mutation cystic fibrosis (nmCF) were published in Lancet Respiratory Medicine. The results demonstrated positive trends in both the primary endpoint, lung function as measured by relative change in % predicted FEV1 (forced expiratory volume in one second) and in the secondary outcome measure, rate of pulmonary exacerbations. The collective data from this trial, including retrospective and subgroup analyses support the conclusion that ataluren was active and showed clinically meaningful improvements over placebo in these trials.

Related Articles


"The overall data from this trial are promising. Patients on ataluren experienced fewer pulmonary exacerbations and showed a stabilization in their FEV1 results, particularly in the subgroup of patients that did not use chronic inhaled aminoglycosides. Such stabilization of disease is an important clinical endpoint, particularly for this patient population that has one of the most severe forms of CF. CF patients with nonsense mutations do not produce any functional CFTR protein and therefore generally have a more severe form of cystic fibrosis. Current treatments for nonsense mutation cystic fibrosis focus on alleviating symptoms and reducing infections, whereas ataluren targets the underlying cause of disease," stated Michael Konstan, M.D., lead study investigator and Chairman of Pediatrics at from University Hospitals Rainbow Babies and & Children's Hospital in Cleveland, Ohio.

The Phase 3 double-blind, placebo-controlled study, which was conducted across 11 countries, compared ataluren (n=116) to placebo (n=116) in nmCF patients. The primary endpoint, the relative change from baseline in %-predicted FEV1 at 48 weeks, showed a positive trend favoring ataluren versus placebo, and a larger effect in patients not receiving chronic inhaled tobramycin. In the intent-to-treat population, there was a 3% difference in the relative change from baseline in %-predicted FEV1 between the ataluren and placebo groups at Week 48 (-2.5% change on ataluren vs. -5.5% change on placebo; p=0.12) which was not statistically significant. An analysis of the relative change from baseline in %-predicted FEV1 across all post-baseline study visits demonstrated an average difference between ataluren and placebo of 2.5% (-1.8% average change on ataluren vs. -4.3% average change on placebo; p= 0.048). There were 23% fewer pulmonary exacerbations in the ataluren group compared to placebo (p=0.0992). Further results from a post hoc analysis of the subgroup of patients not receiving chronic inhaled tobramycin showed a 5.7% difference in relative change from baseline in % predicted FEV1 favoring ataluren, with a mean change from baseline of -0.7% in the ataluren arm, and -- 6.4% in the placebo arm (nominal p=0.0082). In addition, there were 40% fewer exacerbations in ataluren-treated patients in this subgroup. The outcomes observed in multiple endpoints between the subgroup of patients who were not prescribed chronic inhaled tobramycin and the subgroup of patients who were prescribed chronic inhaled tobramycin as well as post-hoc in vitro testing showing the interference of aminoglycoside antibiotics with ataluren activity support the hypothesis that inhaled tobramycin may interfere with ataluren's mechanism of action.

Safety results indicate that ataluren was generally well tolerated. The overall incidence of adverse events through Week 48 was similar in the ataluren and placebo groups, except for the occurrence of creatinine elevations that occurred more frequently in the ataluren group in connection with concomitant treatment with systemic aminoglycosides. Most treatment emergent adverse events were of mild (Grade 1) or moderate (Grade 2) severity, and no life-threatening adverse events were reported. Most serious adverse events reported in this study were CF pulmonary exacerbations and were considered unrelated to ataluren treatment. Eight patients in the ataluren arm and three patients in the placebo arm discontinued treatment due to an adverse event.

"We are very encouraged by the data from this trial. Given spirometry and pulmonary exacerbation results in the subgroup of patients not receiving chronic inhaled tobramycin, and a favorable safety profile, this study supports further clinical testing of ataluren as a potential first-in-class treatment for nmCF patients not receiving chronic inhaled tobramycin," stated Stuart W. Peltz, Ph.D., Chief Executive Officer of PTC Therapeutics, Inc. "We look forward to initiating a confirmatory ataluren trial in nmCF patients later this year."


Story Source:

The above story is based on materials provided by University Hospitals Case Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Eitan Kerem, Michael W Konstan, Kris De Boeck, Frank J Accurso, Isabelle Sermet-Gaudelus, Michael Wilschanski, J Stuart Elborn, Paola Melotti, Inez Bronsveld, Isabelle Fajac, Anne Malfroot, Daniel B Rosenbluth, Patricia A Walker, Susanna A McColley, Christiane Knoop, Serena Quattrucci, Ernst Rietschel, Pamela L Zeitlin, Jay Barth, Gary L Elfring, Ellen M Welch, Arthur Branstrom, Robert J Spiegel, Stuart W Peltz, Temitayo Ajayi, Steven M Rowe. Ataluren for the treatment of nonsense-mutation cystic fibrosis: a randomised, double-blind, placebo-controlled phase 3 trial. The Lancet Respiratory Medicine, 2014; DOI: 10.1016/S2213-2600(14)70100-6

Cite This Page:

University Hospitals Case Medical Center. "Ataluren Phase 3 trial results in nonsense mutation cystic fibrosis." ScienceDaily. ScienceDaily, 16 May 2014. <www.sciencedaily.com/releases/2014/05/140516203344.htm>.
University Hospitals Case Medical Center. (2014, May 16). Ataluren Phase 3 trial results in nonsense mutation cystic fibrosis. ScienceDaily. Retrieved December 22, 2014 from www.sciencedaily.com/releases/2014/05/140516203344.htm
University Hospitals Case Medical Center. "Ataluren Phase 3 trial results in nonsense mutation cystic fibrosis." ScienceDaily. www.sciencedaily.com/releases/2014/05/140516203344.htm (accessed December 22, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Monday, December 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Christmas Kissing Good for Health

Christmas Kissing Good for Health

Reuters - Innovations Video Online (Dec. 22, 2014) Scientists in Amsterdam say couples transfer tens of millions of microbes when they kiss, encouraging healthy exposure to bacteria. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Brain-Dwelling Tapeworm Reveals Genetic Secrets

Brain-Dwelling Tapeworm Reveals Genetic Secrets

Reuters - Innovations Video Online (Dec. 22, 2014) Cambridge scientists have unravelled the genetic code of a rare tapeworm that lived inside a patient's brain for at least four year. Researchers hope it will present new opportunities to diagnose and treat this invasive parasite. Matthew Stock reports. Video provided by Reuters
Powered by NewsLook.com
Touch-Free Smart Phone Empowers Mobility-Impaired

Touch-Free Smart Phone Empowers Mobility-Impaired

Reuters - Innovations Video Online (Dec. 21, 2014) A touch-free phone developed in Israel enables the mobility-impaired to operate smart phones with just a movement of the head. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Earthworms Provide Cancer-Fighting Bacteria

Earthworms Provide Cancer-Fighting Bacteria

Reuters - Innovations Video Online (Dec. 21, 2014) Polish scientists isolate bacteria from earthworm intestines which they say may be used in antibiotics and cancer treatments. Suzannah Butcher reports. Video provided by Reuters
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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