TABLE 1.
Compounds discontinued during clinical development for DMD.
| Compound | Mechanism | Route | Phase | N | Cohort age | Primary efficacy endpoint | Reason of discontinuation | Signal of efficacy | Identifier (clinicaltrials.gov) |
|---|---|---|---|---|---|---|---|---|---|
| drisapersen/PRO051/BMN051/GSK2402968 (or Kyndrisa) | skipping of exon 51 | SC | III | 186 | ≥5 | 6MWT | safety/efficacy | improvements in 6MWT in population with a baseline 6MWT of 300–400 m | NCT01254019 |
| PRO044/BMN044 | skipping of exon 44 | IV/SC | I/II | 18 | 5–16 | safety, dystrophin expression | linked with drisapersen | - | NCT01037309 |
| PRO045/BMN045 | skipping of exon 45 | SC | I/II | 15 | 5–18 | 6MWT | linked with drisapersen | - | NCT01826474 |
| PRO053/BMN053 | skipping of exon 53 | IV/SC | I/II | 9 | 5–18 | 6MWT | linked with drisapersen | - | NCT01957059 |
| suvodirsen/WVE-210201 | skipping of exon 51 | IV | II/III | 6 | 5–12 | dystrophin expression, NSAA | PK | - | NCT03907072 |
| domagrozumab/PF-06252616 | myostatin inhibition | IV | II | 121 | 6–15 | safety, 4SC | efficacy | increased muscle mass, improvement on NSAA | NCT02310763 |
| ACE-031 | myostatin inhibition | SC | II | 24 | ≥4 | safety | safety | increased lean body mass, improvement on 6MWT | NCT01099761 |
| talditercept alfa/RG6206/ RO7239361 |
myostatin inhibition | SC | II/III | 166 | 6–11 | NSAA | efficacy | increased lean body mass | NCT03039686 |
| tadalafil | vasodilation | oral | III | 331 | 7–14 | LVESV on CMR imaging | efficacy | decreased decline on PUL in older subjects | NCT01865084 |
| sidenafil | vasodilation | oral | II | 20* | 18–50 | FVC %predicted | safety | - | NCT01168908 |
| idebenone | Q10 analogue/antioxidant action | oral | III | 256 | ≥10 | FVC | efficacy | improved respiratory function in steroid-naïve population | NCT02814019 |
| ezutromid/SMT C1100 | utrophin upregulation | oral | II | 40 | ≥5 | MRI-T2 and fat fraction for leg muscles | efficacy/PK | improved parameters on imaging, increased utrophin levels on biopsies | NCT02858362 |
| edasalonexent/CAT-1004 | NF-kB inhibitor/anti-inflammatory action | oral | III | 131 | 4–7 | safety, NSAA | efficacy | improvements in NSAA in younger population | NCT03703882 |
| MNK-1411/cosyntropin | anti-inflammatory action | SC | II | 44 | 4–8 | 10 MW/R | slow recruitment | - | NCT03400852 |
| HT-100/halofuginone | anti-inflammatory/anti-fibrotic action | oral | I/II | 17 | 6–20 | safety | safety | - | NCT01847573 |
| P-188NF | membrane stability | SC | II | 10 | 12–25 | FVC | drug supply | - | NCT03558958 |
*including patients with Becker muscular dystrophy.
CMR, cardiac magnetic resonance; SC, subcutaneous; IV, intravenous; 6MWT, 6-Minute Walk Test; NSAA, North Star Ambulatory Assessment; 4SC, 4 Stair Climb Time; LVESV, left ventricular end-systolic volume; FVC, forced vital capacity; MRI-T2, transverse relaxation time on MRI; 10MW/R, 10 Meter Walk/Run; PK, pharmacokinetics.