Abstracts / Neuromuscular Disorders 29 (2019) S37–S208 S167 group (1.25, 5 and 20 mg/kg) and one patient in 20 mg/kg group showed high efﬁciency of exon 53 skipping and expression of dystrophin protein (Sci Transl Med. 10, eaan0713 (2018)). Phase I/II dose-ﬁnding, multicenter study (Study No: NS065/NCNP-01-P1/2, JapicCTI-163291) enrolled 16 Japanese DMD patients, age of 5-12 years, amenable to exon 53 skipping. Patients were assigned to 40 or 80mg/kg dose group and received weekly infusions of viltolarsen for 24 weeks. We previously reported that 40 and 80 mg/kg of viltolarsen was well tolerated and no adverse event leading to discontinuation. In addition, western blotting analysis of dystrophin protein in muscle demonstrated signiﬁcant dystrophin protein expression and Exon 53 skipping level showed tendency to increase depend on dose and treatment duration, which corresponded to mechanism of action of viltolarsen. And the correlation analysis showed higher dystrophin tended to suppress the decrease of motor functions (Time to stand and 10m Run/walk). In order to investigate further clinical beneﬁt of viltolarsen, we exploratory performed additional analysis including the assessment of relationships between change of dystrophin and quantitative muscle strength. http://dx.doi.org/10.1016/j.nmd.2019.06.454 P.341 A phase 2 randomized placebo-control trial of domagrozumab in boys with Duchenne muscular dystrophy (DMD) S. Marrafﬁno 1 , M. Binks 1 , J. Palmer 1 , S. Sherlock 2 , V. Purohit 3 , L. Charnas 1 1 Pﬁzer, Inc, Cambridge MA, USA; 2 Pﬁzer, Inc., Cambridge MA, USA; 3 Pﬁzer, Inc., Groton CT, USA Domagrozumab (doma), a myostatin inhibitor, was evaluated in a randomized, blinded, placebo-controlled trial for safety and efﬁcacy as a potential treatment for DMD. Approach: 120 ambulatory boys with DMD (aged 6 to 15 years) were enrolled and treated with doma (n=80) or placebo (n=40). The primary efﬁcacy endpoint was mean change in 4 stair climb (4SC) at week 49. The secondary efﬁcacy endpoints included NSAA, 6MWD, FVC, strength and PUL. Mean (SD) age was 8.4 (1.7) and 9.3 (2.3) years in doma treated patients and placebo respectively. The difference in mean (95% CI) change from baseline (CBL) on 4SC at Week 49 for doma vs placebo was 0.27 (-7.4, 7.9) seconds (P=0.94). The CBL on NSAA total score at Week 49 for doma vs placebo was 1.6 (-0.5, 3.8), P=0.13. Exploratory analyses of the NSAA including the time-to-loss of individual items (survival) and cumulative number of items lost suggest other methods to assess the NSAA. There were no statistically signiﬁcant differences between treatment arms on all other secondary clinical endpoints. 118 patients had adverse events (AEs) on study; 14 had severe AEs. Serious AEs occurred in 5 patients. Mean cardiac troponin I was elevated at baseline and similarly across treatments arms throughout the trial and therefore deemed unrelated to doma treatment. Mean left ventricular ejection fraction (LVEF) declined in all groups, but was greater at Week 97 in patients treated with doma continuously for 96 weeks (CBL - 3.9%) vs patients who received 48 weeks of treatment with doma and 48 weeks of PBO (CBL -1.6% and -0.9%). The systemic exposures of domagrozumab provided adequate target coverage. Doma was generally safe and well tolerated. Efﬁcacy measures did not support a signiﬁcant treatment effect. Based on the totality of evidence, this trial and an open-label extension study were terminated. http://dx.doi.org/10.1016/j.nmd.2019.06.455 P.342 Ataluren for treating Duchenne muscular dystrophy with a nonsense mutation in the dystrophin gene – evaluation through a managed access agreement V. Ayyar-Gupta 1 , D. Ridout 1 , A. Manzur 2 , F. Muntoni 1 , N. Study Group 3 1 University College London, London, UK; 2 Great Ormond Street Hospital, London, UK; 3 Northstar Clinical Network, UK About 10-15% of Duchenne muscular dystrophy (DMD) patients have a nonsense mutation. The drug Ataluren is a mutation speciﬁc therapy developed by PTC therapeutics to target this mutation to treat the underlying cause of DMD. Based on the clinical and economic evidence from the evaluation of the drug, and the signiﬁcance of the beneﬁts placed by patients, carers and clinical experts, a managed access agreement (MAA) was established with NICE, NHS England, PTC therapeutics, patient community and clinical experts to evaluate the long term effects of the drug and review continued use of the treatment. The Northstar clinical network collects and holds the data for review for this MAA. This abstract aims to describe the characteristics of the current patient cohort in the MAA. The MAA enrols DMD patients with nonsense mutation aged 5 years and over who are able to walk 10 steps unaided, from 15 centres across England. Upon signing the MAA consent, Ataluren is prescribed to patients with the criteria to stop the treatment within six months of reaching a non-ambulatory status. Patient’s age, steroid use, NSAA, quality of life data (CUH9, EQ5D) and details of the drug are collected at six monthly intervals. 77 patients have been enrolled into the MAA since August 2016. At enrolment (baseline), the mean age of the patients was 8 years, 56 patients were on an intermittent or daily regime of steroids, with an average of 41 months of steroid use. The mean NSAA at baseline was 20.7. This is an observational study without randomisation. Propensity score matching will be used to minimise bias in comparing the change in the NSAA total score, over a 4-year period between the Ataluren cohort and concurrent control patients. Baseline matching factors will include age, steroid use duration (< 1 year, or >1 year), steroid regimen, steroid type, and baseline NSAA total score; with an aim for a 1-1 match. Availability of Ataluren as treatment for DMD in the NHS will be based on the ﬁndings of this MAA, and subsequent recommendations from NICE. http://dx.doi.org/10.1016/j.nmd.2019.06.456 FUKUYAMA CONGENITAL MUSCULAR DYSTROPHY P.343 Complications of Fukuyama congenital muscular dystrophy revealed from a nationwide registry K. Ishigaki 1 , C. Ihara 2 , H. Nakamura 3 , M. Mori-Yoshimura 4 , K. Maruo 5 , T. Murakami 1 , T. Sato 1 , M. Shichiji 1 , K. Ishiguro 1 , S. Nagata 1 , H. Kaiya 2 , M. Osawa 1 1 Tokyo Women’s Medical University, Tokyo, Japan; 2 JMDA, Tokyo, Japan; 3 NCNP, Tokyo, Japan; 4 National Center Hospital, NCNP, Tokyo, Japan; 5 University of Tsukuba, Ibaraki, Japan Fukuyama congenital muscular dystrophy (FCMD), the most common CMD in Japan, features cortical migration defects. In 2013, the Japan Muscular Dystrophy Association developed an FCMD patient registry. From October 2011 through September 2013, 207 Japanese FCMD patients (104 males, 103 females) in total were registered (aged 0-42 years). A homozygous founder 3-kb insertion mutation in the FKTN gene was present in 80% of registrants, while 20% had a compound heterozygous mutation. We retrospectively analyzed complications and clinical care based on the registry database. Thirty-three percent of patients (69/207) experienced febrile seizures and/or epilepsy, and 24.6% (51/207) had been treated with antiepileptic drugs. Ocular abnormalities were reported in 28.5% (59/207) of patients. Myopia was the most frequently detected abnormality, present (8.7%), followed by strabismus (5.9%), cataracts (1.1%), retinal detachment, optic nerve atrophy and others. Cardiac dysfunction was detected in 16% (33/207) of patients. Overall, 12.6% of patients (26/207) were treated for cardiac dysfunction; 73% of patients received angiotensin-converting enzyme (ACE) inhibitors, 50% received beta-blockers, 19.2% received diuretics, and 7.7% received angiotensin II receptor blockers. Sixteen percent of patients (34/207) required respiratory support. Non-invasive positive pressure ventilation was initiated in 14% (29/207); only 6.8% of these patients (2/29) depended on 24-h ventilator support, and the other 90% (27/29) needed ventilation only during sleep. Overall, 2.4% of patients (5/207) required a