Santhera reported positive results from the double-blind, randomized, placebo-controlled Phase III study (DELOS) in 65 Duchenne boys aged between 10 and 18 years who were not using concomitant corticosteroids. The outcomes provide clear evidence of a clinical benefit for Catena®/Raxone® in delaying the loss of respiratory function in patients with DMD compared to placebo.
The DELOS trial met the primary endpoint, the difference between Catena®/Raxone® and placebo in the change from baseline to week 52 in Peak Expiratory Flow (PEF as percent predicted, PEF%p). Peak Expiratory Flow is a measure of respiratory muscle strength, the decline of which is a major contributing factor to morbidity and mortality in DMD. Hospital-based spirometry assessments demonstrated that Catena®/Raxone® significantly reduced the annual decline in PEF%p by 66% compared to patients taking placebo.
Catena®/Raxone® also significantly reduced the annual decline in PEF%p by 80% compared to patients taking placebo as measured weekly by the patient at home using the hand-held ASMA-1 device (secondary endpoint). Furthermore, Catena®/Raxone® significantly reduced the annual decline of Forced Expiratory Volume in 1 second by 78% compared to patients taking placebo. Importantly, the outcome for Forced Vital Capacity, a measure of restrictive lung disease predictive of morbidity and mortality in DMD, also supported a treatment benefit of Catena®/Raxone®. The annual decline in FVC%p was reduced by 37% in Catena®/Raxone®-treated patients.
Catena®/Raxone® (900 mg/day) was safe and well tolerated with adverse event rates comparable to placebo.
For a description of the DELOS results, click here Buyse et al: Efficacy of idebenone on respiratory function in patients with Duchenne muscular dystrophy not using glucocorticoids (DELOS): a double-blind randomised placebo-controlled phase 3 trial. Lancet 2015; 385: 1748-57.
ptct had almost nothing as far as data and also showed very very little help in dmd improvement and they got approved ..huh
PTCT seems to have a very tiny positive effect for about a year but they got it approved...If ever Sarepta gets approved that stock ptct will drop like a rock.r
The so-called six-minute walk test was the primary outcome measure for this 174-person, 48-week trial. At the end of the trial, all participants had lost some walking ability, as measured by the distance they could cover in six minutes.
However, after about a year, those in the low-dose ataluren group were able to walk an average of 29.7 meters (about 97 feet) further than those in the placebo group. The high-dose group, by contrast, walked on average the same distance in six minutes as the placebo group.
Participants were ambulatory males who were at least 5 years old. Thirty-seven trial sites in North America, Europe, Australia and Israel were part of this study.
The low-dose group received oral ataluren at 10 milligrams per kilogram of body weight each morning and at midday and 20 milligrams per kilogram in the evening. The high-dose group received 20 milligrams per kilogram in the morning and at midday and 40 milligrams per kilogram in the evening. The placebo group received a look-alike, inert substance.
The six-minute walk test was the primary outcome measure, but other outcomes were also assessed, including safety, muscle function and strength, and muscle dystrophin levels.
Ataluren was generally well tolerated, and adverse events were similar across all treatment groups. Serious adverse events were infrequent, and none were considered related to the drug.
The trial results suggested "positive trends" in muscle function, as measured by timed function tests, in those receiving the low-dose regimen of ataluren compared to those receiving a placebo, PTC said.
PTC said dystrophin protein expression could not be properly assessed, in part because of technical limitations. The company said no relationship could be established between dystrophin levels and distance covered in the six-minute walk tes
Dystrophin was also restored in the diaphragm and other accessory respiratory muscles, intercostal (IM) and sternomastoid (SM) as well as tibialis anterior (TA) of the lower limb. Again immunohistological staining demonstrated extensive dystrophin protein restoration (Supplementary Fig. 3 A) with exceptionally high recovery scores between 74–104% (Supplementary Fig. 4). The RT-qPCR (Supplementary Fig. 3 B) and western blot quantification (Supplementary Fig. 3 C&6) exhibited similar results with very high dystrophin transcript levels (77–86%) and between 58–101% restoration of dystrophin protein in the diaphragm, TA, IM and SM muscles. RT-PCR also showed complete skipping of exon 23 in these muscles (Supplementary Fig. 5). This demonstrates that the repeated low-dose Pip6f-PMO administration protocol successfully restored high levels of dystrophin in skeletal and cardiac muscles.
Exercised mdx mice exhibit dilated cardiomyopathy
The cardiac phenotype in 6 month old mdx mice is mild, but may be aggravated by exercise33, 34. A forced exercise regimen was undertaken in control wild type C57BL/10 mice (n = 10) and mdx mice both untreated (n = 9) and treated with Pip6f-PMO (n = 10). From 12 weeks of age, mice were exercised on a treadmill 3 times every 2 weeks for 45 minutes (Supplementary Fig. 2). 10 mdx and 10 C57BL/10 unexercised mice were used as controls to monitor the effects of exercise alone. Mdx mice failed to run consistently, as they stopped intermittently and required constant encouragement (Supplementary Video 1). Indeed, 3 untreated mdx mice were removed from the study as they exhibited severe aversions to running, thereby reducing the sample size from 12 to 9 mice, which demonstrates their poor running capacity. C57BL/10 mice were markedly more active than their mdx counterparts (Supplementary Video 2).
All groups of mice underwent cine-MRI at 24 weeks of age, 5 days after the last exercise event in the exercised groups.
American Academy of Neurology [AAN] Washington D. C. April 18-25
From the program listing - site says over 2500 abstracts - these are one's I picked out using the search term "duchenne".
Meeting schedule - Thursday April 23
Developing Antisense Oligomers as a Genetic Therapy for Duchenne Muscular Dystrophy
Francesco Muntoni, MD University College London Institute of Child Health, London, United Kingdom
Poster Session II Tuesday April 21
P2.006 Utrophin Modulators to Treat Duchenne Muscular Dystrophy (DMD): Phase 1b Clinical Trial Results of SMT C1100 Jon Tinsley, Francesco Muntoni, Stefan Spinty, Helen Roper, Imelda Hughes, Valeria Ricotti, Alison Bracchi, Bina Tejura, David Roblin, Gary Layton, Kay Davies
P2.230 Drisapersen: An Overview of the Exon-51 Skipping Antisense Oligonucleotide Clinical Program to Date in Duchenne Muscular Dystrophy (DMD) Craig McDonald, Nathalie Goemans, Thomas Voit, Rosamund Wilson, Claire Wardell, Giles Campion
P2.238 Evaluating the Progression of Physical Impairment, Activity Limitation and Quality of Life in Duchenne Muscular Dystrophy (DMD): A Prospective Natural History Study Nathalie Goemans, Brenda Wong, Craig McDonald, Ali Jones, Caroline Mason, Giles Campion
P2.240 Pooled Analyses of Efficacy Parameters in Patients with Duchenne Muscular Dystrophy (DMD): Results from the Drisapersen (DRIS) Clinical Trial Program Nathalie Goemans, Thomas Voit, Craig McDonald, Rosamund Wilson, Claire Wardell, Giles Campion
Poster Session V Wednesday April 22
P5.052 Skeletal Muscle, Cardiac, and Pulmonary Imaging Biomarkers of Disease Activity in a Trial of Exon-skipping for Boys with Duchenne Muscular Dystrophy Ami Mankodi, Robert Janiczek, Noura Azzabou, Lasya Gaur, Courtney Bishop, Harmen Reyngoudt, Martijn Froeling, Rexford Newbould, Andrew Arai, Pierre Carlier, Kenneth Fischbeck
P5.061 In Vitro Pharmacokinetic Evaluation of Eteplirsen, SRP-4045, and SRP-4053;
Biotech is super growing and it is hard to get anyone these days.You will see many mergers and many biotechs will be bought out over the next few years even sarepta.
20150080311 03/19/15 Compound and treating myotonic dystrophy
2 20150080340 03/19/15 Boronic acid conjugates of oligonucleotide analogues
3 20150073140 03/12/15 Oligonucleotide analogues having modified intersubunit linkages and/or terminal groups
4 20150038462 02/05/15 Oligonucleotide analog and treating flavivirus infections
5 20140329762 11/06/14 Compositions for treating muscular dystrophy
6 20140329772 11/06/14 Induced exon inclusion in spinal muscle atrophy
7 20140329881 11/06/14 Exon skipping compositions for treating muscular dystrophy
8 20140330006 11/06/14 Functionally-modified oligonucleotides and subunits thereof
9 20140323544 10/30/14 Exon skipping compositions for treating muscular dystrophy
10 20140315862 10/23/14 Compositions for treating muscular dystrophy
11 20140315977 10/23/14 Exon skipping compositions for treating muscular dystrophy
12 20140303073 10/09/14 Antisense antiviral compound and treating influenza viral infection
13 20140303238 10/09/14 Oligonucleotides for treating expanded repeat diseases
14 20140296321 10/02/14 Methods and compositions for manipulating translation of protein isoforms from alternative initiation of start sites
15 20140287983 09/25/14 Antisense compositions and methods for modulating contact hypersensitivity or contact dermatitis
16 20140213737 07/31/14 Antibacterial antisense oligonucleotide and method
17 20140194612 07/10/14 Immunosuppression compound and treatment method
18 20140107013 04/17/14 Compound and treating myotonic dystrophy
19 20140094500 04/03/14 Multiple exon skipping compositions for dmd
20 20140045916 02/13/14 Splice-region antisense composition and method
21 20140024821 01/23/14 Oligonucleotide analogues targeting human lmna
22 20130288369 10/31/13 Dsrna molecules comprising oligonucleotide analogs having modified intersubunit linkages and/or terminal groups
23 20130190390 07/25/13 Multiple exon skipping compositions for dmd
OLIGONUCLEOTIDE ANALOGUES HAVING MODIFIED INTERSUBUNIT LINKAGES AND/OR TERMINAL GROUPS
Application number: 20150073140
Abstract: Oligonucleotide analogues comprising modified intersubunit linkages and/or modified 3? and/or 5?-end groups are provided. The disclosed compounds are useful for the treatment of diseases where inhibition of protein expression or correction of aberrant mRNA splice products produces beneficial therapeutic effects.
Filed: June 6, 2014
Issued: March 12, 2015
Assignee: Sarepta Therapeutics, Inc.
''all belongs to Sarepta''
and don't care about nothing but their pennies.
This will confirm 100 percent what the FDA is looking for ''same as the old 12 boy trial path.Could be the end of may but june for sure.
The FDA was looking for data like this ''class approval''drug the same ,only the sequence is different..It is the same safety as well.
-------------XXXX----DMD is a rare, X-linked recessive, degenerative neuromuscular disorder that causes severe progressive muscle loss leading to premature death. The disease is caused by mutations in the DMD gene that disrupt the reading frame of the encoded dystrophin mRNA resulting in a lack of dystrophin, a protein that plays a key structural role in muscle fibers. Sarepta’s Phosphorodiamidate Morpholino Oligomer (PMO) chemistry and exon-skipping technology directs alternative splicing of the dystrophin pre-mRNA to restore the mRNA reading frame and enable translation of an internally truncated yet functional dystrophin protein. Eteplirsen, Sarepta’s lead investigational exon-skipping drug candidate, is designed to address deletion mutations amenable to exon 51 skipping (13[percnt] of total DMD population). SRP-4045 and SRP-4053 are additional exon skipping drug candidates in development designed to skip exons 45 or 53 respectively, addressing an additional 16[percnt] of the total DMD population (~8[percnt] each). DESIGN/METHODS: Studies conducted to evaluate the in vitro pharmacokinetic properties of each PMO include plasma protein binding and metabolic stability in hepatic microsomes of mice, rats, monkeys, and humans. Induction and inhibition of cytochrome P450 isoenzymes were also evaluated. RESULTS: Pharmacokinetic profiles for the three PMOs were similar. Each exhibited low protein binding in all species, no evidence of in vitro metabolism by hepatic microsomes, no extensive inhibition of the major drug metabolizing cytochrome P450 isoenzymes CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP3A4/5, and no induction of CYP1A2, CYP2B6, or CYP3A4 at biologically relevant concentrations in vitro. CONCLUSIONS: The in vitro pharmacokinetic profiles of eteplirsen, SRP-4045 and SRP-4053 were similar and showed no significant interaction with total serum protein or metabolic enzymes. Study Supported by: Sarepta Therapeutics XXXXX----XXXXXX---XXXXXXXXX-----
April 22, 2015
Neuromuscular Disease: Pathogenesis and Pathology
In Vitro Pharmacokinetic Evaluation of Eteplirsen, SRP-4045, and SRP-4053; Three Phosphorodiamidate Morpholino Oligomers (PMO) for the Treatment of Patients with Duchenne Muscular Dystrophy (DMD) (P5.061)