***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: This 48-week , r and omized , placebo-controlled phase 3 study ( DMD114044 ; NCT01254019 ) evaluated efficacy and safety of subcutaneous drisapersen 6 mg/kg/week in 186 ambulant boys aged ≥5 years , with Duchenne muscular dystrophy ( DMD ) result ing from an exon 51 skipping amenable mutation  . Drisapersen was generally well tolerated , with injection-site reactions and renal events as most commonly reported adverse events . A nonsignificant treatment difference ( P = 0.415 ) in the change from baseline in six-minute walk distance ( 6MWD ; primary efficacy endpoint ) of 10.3 meters in favor of drisapersen was observed at week 48 . Key secondary efficacy endpoints ( North Star Ambulatory Assessment , 4-stair climb ascent velocity , and 10-meter walk/run velocity ) gave consistent findings . Lack of statistical significance was thought to be largely due to greater data variability and subgroup heterogeneity . The increased st and ard deviation alone , due to less stringent inclusion /exclusion criteria , reduced the statistical power from pre-specified 90 % to actual 53 % . Therefore , a post-hoc analysis was performed in 80 subjects with a baseline 6MWD 300 - 400 meters and ability to rise from floor . A statistically significant improvement in 6MWD of 35.4 meters ( P = 0.039 ) in favor of drisapersen was observed in this sub population . Results suggest that drisapersen could have benefit in a less impaired population of DMD subjects Summary Background We report clinical safety and biochemical efficacy from a dose-ranging study of intravenously administered AVI-4658 phosphorodiami date morpholino oligomer ( PMO ) in patients with Duchenne muscular dystrophy . Method We undertook an open-label , phase 2 , dose-escalation study ( 0·5 , 1·0 , 2·0 , 4·0 , 10·0 , and 20·0 mg/kg bodyweight ) in ambulant patients with Duchenne muscular dystrophy aged 5–15 years with amenable deletions in DMD . Participants had a muscle biopsy before starting treatment and after 12 weekly intravenous infusions of AVI-4658 . The primary study objective was to assess safety and tolerability of AVI-4658 . The secondary objectives were pharmacokinetic properties and the ability of AVI-4658 to induce exon 51 skipping and dystrophin restoration by RT-PCR , immunohistochemistry , and immunoblotting . The study is registered , number NCT00844597 . Findings 19 patients took part in the study .  AVI-4658 was well tolerated with no drug-related serious adverse events  . AVI-4658  induced exon 51 skipping in all cohorts and new dystrophin protein expression in a significant dose-dependent ( p=0·0203 ) , but variable , manner in boys from cohort 3 ( dose 2 mg/kg ) onwards . Seven patients responded to treatment , in whom mean dystrophin fluorescence intensity increased from 8·9 % ( 95 % CI 7·1–10·6 ) to 16·4 % ( 10·8–22·0 ) of normal control after treatment ( p=0·0287 ) . The three patients with the greatest responses to treatment had 21 % , 15 % , and 55 % dystrophin-positive fibres after treatment and these findings were confirmed with western blot , which showed an increase after treatment of protein levels from 2 % to 18 % , from 0·9 % to 17 % , and from 0 % to 7·7 % of normal muscle , respectively . The dystrophin-associated proteins α-sarcoglycan and neuronal nitric oxide synthase were also restored at the sarcolemma . Analysis of the inflammatory infiltrate indicated a reduction of cytotoxic T cells in the post-treatment muscle biopsies in the two high-dose cohorts . Interpretation The safety and biochemical efficacy that we present show the potential of AVI-4658 to become a disease-modifying drug for Duchenne muscular dystrophy . Funding UK Medical Research Council ; AVI BioPharma BACKGROUND Cardiorespiratory failure is the leading cause of death in Duchenne muscular dystrophy . Based on pre clinical and phase 2 evidence , we assessed the efficacy and safety of idebenone in young patients with Duchenne muscular dystrophy who were not taking concomitant glucocorticoids . METHODS In a multicentre phase 3 trial in Belgium , Germany , the Netherl and s , Switzerl and , France , Sweden , Austria , Italy , Spain , and the USA , patients ( age 10 - 18 years old ) with Duchenne muscular dystrophy were r and omly assigned in a one-to-one ratio with a central interactive web response system with a permuted block design with four patients per block to receive idebenone ( 300 mg three times a day ) or matching placebo orally for 52 weeks . Study personnel and patients were masked to treatment assignment . The primary endpoint was change in peak expiratory flow ( PEF ) as percentage predicted ( PEF%p ) from baseline to week 52 , measured with spirometry . Analysis was by intention to treat ( ITT ) and a modified ITT ( mITT ) , which was prospect ively defined to exclude patients with at least 20 % difference in the yearly change in PEF%p , measured with hospital-based and weekly home-based spirometry . This study is registered with Clinical Trials.gov , number NCT01027884 . FINDINGS 31 patients in the idebenone group and 33 in the placebo group comprised the ITT population , and 30 and 27 comprised the mITT population . Idebenone significantly attenuated the fall in PEF%p from baseline to week 52 in the mITT ( -3·05%p [ 95 % CI -7·08 to 0·97 ] , p=0·134 , vs placebo -9·01%p [ -13·18 to -4·84 ] , p=0·0001 ; difference 5·96%p [ 0·16 to 11·76 ] , p=0·044 ) and ITT population s ( -2·57%p [ -6·68 to 1·54 ] , p=0·215 , vs -8·84%p [ -12·73 to -4·95 ] , p<0·0001 ; difference 6·27%p [ 0·61 to 11·93 ] , p=0·031 ) . Idebenone also had a significant effect on PEF ( L/min ) , weekly home-based PEF , FVC , and FEV1 . The effect of idebenone on respiratory function outcomes was similar between patients with previous corticosteroid use and steroid-naive patients . Treatment with idebenone was safe and well tolerated with adverse event rates were similar in both groups . Nasopharyngitis and headache were the most common adverse events ( idebenone , eight [ 25 % ] and six [ 19 % ] of 32 patients ; placebo , nine [ 26 % ] and seven [ 21 % ] of 34 patients ) . Transient and mild diarrhoea was more common in the idebenone group than in the placebo group ( eight [ 25 % ] vs four [ 12 % ] patients ) . INTERPRETATION Idebenone reduced the loss of respiratory function and represents a new treatment option for patients with Duchenne muscular dystrophy . FUNDING Santhera Pharmaceuticals BACKGROUND Local intramuscular administration of the antisense oligonucleotide PRO051 in patients with Duchenne 's muscular dystrophy with relevant mutations was previously reported to induce the skipping of exon 51 during pre-messenger RNA splicing of the dystrophin gene and to facilitate new dystrophin expression in muscle-fiber membranes . The present phase 1 - 2a study aim ed to assess the safety , pharmacokinetics , and molecular and clinical effects of systemically administered PRO051 . METHODS We administered weekly abdominal subcutaneous injections of PRO051 for 5 weeks in 12 patients , with each of four possible doses ( 0.5 , 2.0 , 4.0 , and 6.0 mg per kilogram of body weight ) given to 3 patients . Changes in RNA splicing and protein levels in the tibialis anterior muscle were assessed at two time points . All patients subsequently entered a 12-week open-label extension phase , during which they all received PRO051 at a dose of 6.0 mg per kilogram per week . Safety , pharmacokinetics , serum creatine kinase levels , and muscle strength and function were assessed . RESULTS The most common adverse events were irritation at the administration site and , during the extension phase , mild and variable proteinuria and increased urinary α(1)-microglobulin levels ; there were no serious adverse events . The mean terminal half-life of PRO051 in the circulation was 29 days . PRO051 induced detectable , specific exon-51 skipping at doses of 2.0 mg or more per kilogram . New dystrophin expression was observed between approximately 60 % and 100 % of muscle fibers in 10 of the 12 patients , as measured on post-treatment biopsy , which increased in a dose-dependent manner to up to 15.6 % of the expression in healthy muscle . After the 12-week extension phase , there was a mean ( ±SD ) improvement of 35.2±28.7 m ( from the baseline of 384±121 m ) on the 6-minute walk test . CONCLUSIONS Systemically administered PRO051 showed dose-dependent molecular efficacy in patients with Duchenne 's muscular dystrophy , with a modest improvement in the 6-minute walk test after 12 weeks of extended treatment . ( Funded by Prosensa Therapeutics ; Netherl and s National Trial Register number , NTR1241 . ) Despite long-st and ing critiques of the conduct of underpowered clinical trials , the practice not only remains widespread , but also has garnered increasing support . Patients and healthy volunteers continue to participate in research that may be of limited clinical value , and authors recently have offered 2 related arguments to support the validity and value of underpowered clinical trials : that meta- analysis may " save " small studies by providing a means to combine the results with those of other similar studies to enable estimates of an intervention 's efficacy , and that although small studies may not provide a good basis for testing hypotheses , they may provide valuable estimates of treatment effects using confidence intervals . In this article , we examine these arguments in light of the distinctive moral issues associated with the conduct of underpowered trials , the disclosures that are owed to potential participants in underpowered trials so they may make autonomous enrollment decisions , and the circumstances in which the prospect s for future meta-analyses may justify individually underpowered trials . We conclude that underpowered trials are ethical in only 2 situations : small trials of interventions for rare diseases in which investigators document explicit plans for including their results with those of similar trials in a prospect i ve meta- analysis , and early-phase trials in the development of drugs or devices , provided they are adequately powered for defined purpose s other than r and omized treatment comparisons . In both cases , investigators must inform prospect i ve subjects that their participation may only indirectly contribute to future health care benefits Objective : We aim ed to perform an observational study of age at loss of independent ambulation ( LoA  ) and side-effect profiles associated with different glucocorticoid corticosteroid ( GC ) regimens in Duchenne muscular dystrophy ( DMD ) . Methods : We studied 340 participants in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study ( CINRG-DNHS ) . LoA was defined as continuous wheelchair use . Effects of prednisone or prednisolone (PRED)/deflazacort ( DFZ ) , administration frequency , and dose were analyzed by time-varying Cox regression . Side-effect frequencies were compared using χ2 test . Results : Participants treated ≥1 year while ambulatory ( n = 252/340 ) showed a 3-year median delay in LoA ( p < 0.001 ) . Fourteen different regimens were observed . Nondaily treatment was common for PRED ( 37 % ) and rare for DFZ ( 3 % ) . DFZ was associated with later LoA than PRED ( hazard ratio 0.294 ± 0.053 vs 0.490 ± 0.08 , p = 0.003 ; 2-year difference in median LoA with daily administration , p < 0.001 ) . Average dose was lower for daily PRED ( 0.56 mg/kg/d , 75 % of recommended ) than daily DFZ ( 0.75 mg/kg/d , 83 % of recommended , p < 0.001 ) . DFZ showed higher frequencies of growth delay ( p < 0.001 ) , cushingoid appearance ( p = 0.002 ) , and cataracts ( p < 0.001 ) , but not weight gain . Conclusions : Use of DFZ was associated with later LoA and increased frequency of side effects . Differences in st and ards of care and dosing complicate interpretation of this finding , but stratification by PRED/DFZ might be considered in clinical trials . This study emphasizes the necessity of a r and omized , blinded trial of GC regimens in DMD . Classification of evidence 
    Output:
    
Conclusions Current available data do not show evidence that exon-skipping drugs are effective in DMD .
Despite potential effectiveness when used at a specific dose , significant side effects were reported with drisapersen .