Today, Santhera has published the results in the highly prestigious journal, The Lancet, from their successful clinical trial of Raxone®/Catena® . They will present these results later this week, at the annual meeting of the American Academy of Neurology. First, idebenone was safe and well tolerated. Importantly, treatment of study subjects, age 10-18, for one year with Raxone®/Catena® reduced the drop in an important respiratory measurement. The decline in peak expiratory flow was decreased by 66% compared to placebo. In addition, Raxone/Catena had a positive effect on several other respiratory function measures. This is an important and certainly not a modest effect on respiratory function and may well have a substantial effort on quality of life for Duchenne.
This is very exciting news for the Duchenne community on several levels. As the first successful Phase III clinical trial conducted in Duchenne, this is a landmark in and of itself. It also provides an important step for Santhera in seeking regulatory approval and thereby helps provide a path for development of other drugs that address the devastating consequences of Duchenne. Perhaps more importantly, Santhera has demonstrated that trials in the non-ambulatory population are possible, utilizing respiratory measures as primary endpoints. 90% of the young men who participated were in wheelchairs.
To better understand the importance of the respiratory endpoints used in this study, Santhera and PPMD have partnered in a benefit-risk assessment. Benefit-risk assessments include objective studies of the efficacy and risk of therapies, as well as subjective studies of the relative value of these outcomes to the patient. These analyses will help inform regulatory agencies as to the preferences of patients and caregivers for pulmonary outcomes measures, that, in turn, may aid all future trials that assess respiratory function.
Santhera has stated their intent to file for regulatory approval in the U.S. and Europe very soon. PPMD applauds the innovative clinical trial design that Santhera has used and congratulates them on the first successful Phase III clinical trial in Duchenne. We very much look forward to the approval of Raxone®/Catena® and to the potential use of the drug in a combination therapy approach to Duchenne.
Read Santhera's Press Release:
April 21, 2015: Santhera's Positive Phase III Trial (DELOS) in Patients with Duchenne Muscular Dystrophy Published in The Lancet
First successful Phase III trial in DMD shows Raxone®/Catena® preserves respiratory function
Liestal, Switzerland, April 21, 2015 - Santhera Pharmaceuticals (SIX: SANN) announced that the full results of the double-blind placebo-controlled Phase III trial (DELOS) demonstrating efficacy and safety of Raxone®/Catena® (INN: idebenone) in patients with DMD have been published in The Lancet (Lancet 2015; 385: 1748-57. Online publication: http://dx.doi.org/10.1016/S0140-6736(15)60025-3).
The results of the DELOS trial demonstrated that Raxone/Catena significantly reduced the annual decline in Peak Expiratory Flow (PEF as percent predicted, PEF%p) by 66% compared to patients taking placebo. Other respiratory function endpoints such as Forced Vital Capacity (FVC) and Forced Expiratory Volume (FEV1) corroborated these results and showed a consistent pattern with treatment differences supporting efficacy of Raxone/Catena over placebo in the preservation of respiratory function. Researchers concluded that Raxone/Catena represents a new treatment option for DMD patients.
"Publication of the DELOS trial outcome in The Lancet, one of the most prestigious medical journals worldwide, is an extraordinary tribute to this first ever successful phase III trial in DMD", said Gunnar M. Buyse, MD, PhD, Professor of Child Neurology at the University Hospitals Leuven (Belgium) and Principal Investigator for the DELOS trial and lead author of the publication. "It's also a tribute to the hard work of so many scientists, patients and families involved in the 10 years of innovative research in which we have brought idebenone from the lab bench to the patient. Statistically significant and clinically relevant outcomes of primary and secondary endpoints coherently demonstrated that Raxone/Catena reduced the loss of respiratory function and that it was safe and well tolerated. I am very enthusiastic about the positive data from the trial which demonstrate that this drug represents a suitable treatment option to ameliorate a life-threatening complication of the disease."
"With morbidity and mortality in DMD being associated with progressive restrictive lung disease and irreversible loss of lung function, these findings represent an important treatment effect and are of major clinical relevance for patients with DMD", added Craig McDonald, MD, Professor and Chair of the Department of Physical Medicine & Rehabilitation at UC Davis (USA), investigator of the DELOS trial and co-author of the Lancet publication.
"The degree of slowing of respiratory function loss demonstrated in DELOS is of major clinical relevance for patients with DMD", commented Nicholas Coppard, PhD, SVP Development at Santhera. "Based on this benefit and its well-established safety profile, we are very excited about the prospects of Raxone/Catena as a treatment option for DMD patients and we are currently preparing the regulatory filing dossier for application of marketing authorization both in the US and Europe."
About the DELOS trial
DELOS was a Phase III, double-blind, placebo-controlled trial which randomized and treated 64 European and US DMD patients not receiving concomitant corticosteroids. Patients 10-18 years of age received either Raxone/Catena tablets (900 mg/day) or matching placebo for 52 weeks. The primary endpoint was change in Peak Expiratory Flow % predicted (PEF%p) from baseline to week 52. PEF%p declined significantly (-9.01%p; 95% CI: -13.2, -4.8; p<0.001) from baseline to week 52 in the placebo group compared to a non-significant decline (-3.05%p; 95% CI: -7.1, 0.97; p=0.134) in the Raxone/Catena group, resulting in a statistically significant difference between treatment groups of 5.96%p (95% CI: 0.16, 11.8; p=0.044) at week 52 and representing a 66% reduction in loss of PEF%p. A statistically significant treatment effect was also seen at week 26 (p=0.007) and week 39 (p=0.034) and across all assessment timepoints (p=0.018). Data for the primary endpoint were robust across multiple sensitivity analyses and supported by positive outcomes of additional respiratory endpoints.