14 CLINICAL STUDIES

The effect of VYONDYS 53 on dystrophin production was evaluated in one study in DMD patients with a confirmed mutation of the DMD gene that is amenable to exon 53 skipping (Study 1; NCT02310906).

Study 1 Part 1 was a double-blind, placebo-controlled, dose-titration study in 12 DMD patients. Patients were randomized 2:1 to receive VYONDYS 53 or matching placebo. VYONDYS 53-treated patients received four escalating dose levels, ranging from 4 mg/kg/week (less than the recommended dosage) to 30 mg/kg/week, by intravenous infusion for 2 weeks at each dose level.

Study 1 Part 2 was a 168-week, open-label study assessing the efficacy and safety of VYONDYS 53 at a dose of 30 mg/kg/week in the 12 patients enrolled in Part 1, plus 13 additional treatment-naive patients with DMD amenable to exon 53 skipping. At study entry (either in Part 1 or Part 2), patients had a median age of 8 years and were on a stable dose of corticosteroids for at least 6 months. Efficacy was assessed based on change from baseline in the dystrophin protein level (measured as % of the dystrophin level in healthy subjects, i.e., % of normal) at Week 48 of Part 2. Muscle biopsies were obtained at baseline prior to treatment and at Week 48 of Part 2 in all VYONDYS 53-treated patients (n=25), and were analyzed for dystrophin protein level by Sarepta western blot. Mean dystrophin levels increased from 0.10% (SD 0.07) of normal at baseline to 1.02% (SD 1.03) of normal by Week 48 of Study 1 Part 2, with a mean change in dystrophin of 0.92% (SD 1.01) of normal levels (p<0.001); the median change from baseline was 0.88%.

Individual patient dystrophin levels from Study 1 are shown in Table 2.

Table 2: Dystrophin Expression Sarepta Western Blot by Individual Patient From Study 1
Patient Number	Sarepta Western Blot % Normal Dystrophin			Patient number	Sarepta Western Blot % Normal Dystrophin
Patient Number	Baseline	Part 2 Week 48	Change from baseline	Patient number	Baseline	Part 2 Week 48	Change from baseline
1	0.08	0.09	0.01	14	0.22	0.28	0.06
2	0.11	0.11	0.01	15	0.14	0.21	0.07
3	0.21	0.22	0.01	16	0.05	0.42	0.37
4	0.05	0.12	0.08	17	0.07	1.03	0.97
5	0.03	0.12	0.09	18	0.02	1.57	1.55
6	0.06	0.14	0.09	19	0.12	1.17	1.05
7	0.12	0.37	0.25	20	0.03	1.72	1.69
8	0.11	1.06	0.95	21	0.11	1.77	1.66
9	0.06	0.54	0.48	22	0.31	4.30	3.99
10	0.05	0.97	0.92	23	0.11	0.36	0.25
11	0.06	1.55	1.49	24	0.03	0.91	0.88
12	0.07	1.91	1.84	25	0.07	1.29	1.22
13	0.10	3.25	3.15