Open-label extension study
Long-term safety and efficacy are being evaluated in an ongoing extension study1,*
The open-label extension study includes prior clinical trial participants and treatment-naive patients (N=194).
Group 1
Continued on DUVYZAT
(n=110)
Previously treated with DUVYZAT + corticosteroids in a phase 2 clinical trial or EPIDYS
Group 2
Switched from placebo
(n=54)
Previously treated with placebo + corticosteroids in EPIDYS
Group 3
Newly enrolled
(n=30)
Screened for prior trials but not enrolled; started on DUVYZAT in open-label extension
Open-label extension study
Received DUVYZAT + corticosteroids (N=194)†
Baseline characteristics and patient demographics in the open-label extension study were consistent with EPIDYS.
Open-label extension study objectives:
Primary objective:
- To evaluate the long-term safety and tolerability of DUVYZAT in patients with DMD
Key secondary endpoints:
-
Change from baseline at end of each year in:
- Timed function tests (TTRF, 10MWT)
- Motor function and muscle strength as assessed by NSAA
- 6-minute walk test
- Knee extension and elbow flexion
Post hoc analysis:
- Efficacy endpoints evaluated patients taking DUVYZAT against natural history cohorts that were propensity score matched for age, disease stage, and corticosteroid usage (CINRG DNHS and ImagingDMD)
PRIMARY ENDPOINT: SAFETY
Long-term safety of DUVYZAT remained consistent with EPIDYS1
Adverse events in the open-label extension
| Received givinostat throughout (n=110) | Received placebo in prior study (n=54) | Not included in prior study (n=30) | |
|---|---|---|---|
| Adverse event, n (%) | 96 (87.3) | 47 (87.0) | 26 (86.7) |
| Hypertriglyceridemia‡ | 23 (20.9) | 11 (20.4) | 2 (6.7) |
| Fall | 22 (20.0) | 5 (9.3) | 4 (13.3) |
| Diarrhea | 20 (18.2) | 15 (27.8) | 11 (36.7) |
| Thrombocytopenia§ | 19 (17.3) | 19 (35.2) | 5 (16.7) |
| Pyrexia | 19 (17.3) | 7 (13.0) | 2 (6.7) |
| Headache | 16 (14.5) | 9 (16.7) | 6 (20.0) |
| Vomiting | 16 (14.5) | 8 (14.8) | 5 (16.7) |
| Abdominal pain | 12 (10.9) | 9 (16.7) | 1 (3.3) |
| Adverse event considered related to treatment, n (%) | 60 (54.5) | 36 (66.7) | 18 (60.0) |
| Hypertriglyceridemia‡ | 21 (19.1) | 10 (18.5) | 2 (6.7) |
| Thrombocytopenia§ | 19 (17.3) | 18 (33.3) | 5 (16.7) |
| Diarrhea | 10 (9.1) | 9 (16.7) | 10 (33.3) |
| Abdominal pain | 5 (4.5) | 5 (9.3) | 1 (3.3) |
| Serious adverse event, n (%) | 12 (10.9) | 8 (14.8) | 3 (10.0) |
| Femur fracture | 3 (2.7) | 3 (5.6) | 0 |
| Tendinous contracture | 2 (1.8) | 0 | 0 |
| Back pain | 1 (0.9) | 1 (1.9) | 0 |
| Dehydration | 1 (0.9) | 1 (1.9) | 0 |
| Serious adverse event considered related to treatment, n (%) | 0 | 1 (1.9) | 0 |
| Life-threatening or fatal adverse event, n (%) |
0 | 0 | 0 |
| Adverse event leading to study treatment discontinuation, n (%) | 1 (0.9) | 2 (3.7) | 0 |
| Adverse event leading to study withdrawal, n (%) | 1 (0.9) | 2 (3.7) | 0 |
‡ Includes blood triglycerides increased or hypertriglyceridemia.
§ Includes platelet count decreased or thrombocytopenia.
DUVYZAT safety results consistent with findings from EPIDYS.
-
Most patients (169/194) experienced ≥1 adverse event
- Serious adverse events occurred in 23/169 patients and included femur fracture (n=6), tendinous contracture (n=2), back pain (n=2), and dehydration (n=2)
- Severe events occurred in 21/169 patients and included femur fracture (n=4), back pain (n=3), and hypertriglyceridemia‡ (n=2)
- No fatal or life-threatening events
- The most common treatment-related adverse events (hypertriglyceridemia, thrombocytopenia, and diarrhea) typically occurred within the first few weeks of treatment and were manageable with dose modification
- In the open-label extension, patients previously treated with DUVYZAT experienced a lower incidence of diarrhea compared with those newly initiating treatment
- Patients in the open-label extension remained on DUVYZAT for a mean duration >18 months
SECONDARY ENDPOINTS
In the secondary endpoints, baseline function declined and disease progression continued as expected in all 3 groups1
No patients in the open-label extension study received placebo, therefore disease progression was not measured against a comparator.
POST HOC ANALYSIS
Long-term data demonstrate how DUVYZAT helps PROTECT against DMD progression1,∥
DUVYZAT + corticosteroids delayed loss of ambulation compared to natural history cohorts taking corticosteroids
Age at persistent loss of ambulation
NOTE: Patients who did not reach a disease milestone or those who were lost to follow-up were censored on the last date they were known to be in the study.2
DUVYZAT + corticosteroids delayed loss of 4SC ability compared to natural history cohorts taking corticosteroids
Age at persistent loss of 4SC ability
NOTE: Patients who did not reach a disease milestone or those who were lost to follow-up were censored on the last date they were known to be in the study.2
DUVYZAT + corticosteroids delayed loss of ability to rise from the floor compared to natural history cohorts taking corticosteroids
Age at persistent loss of ability to rise from the floor
NOTE: Patients who did not reach a disease milestone or those who were lost to follow-up were censored on the last date they were known to be in the study.2
4SC, 4-stair climb.
∥ As measured by the median difference between DUVYZAT and natural history cohorts. Comparisons were conducted using propensity score–matching methodology. Natural history data were obtained prospectively from multicenter studies (CINRG DNHS and ImagingDMD) and matched to key EPIDYS inclusion criteria.1
References: 1. McDonald CM, Guglieri M, Vučinić D, et al. Long-term evaluation of givinostat in Duchenne muscular dystrophy, and natural history comparisons. Ann Clin Transl Neurol. 2025;12(11):2335-2348. 2. Gomez Andres D, Sansone VA, Phan HC, et al. Givinostat efficacy in Duchenne muscular dystrophy: natural history comparison applying propensity score matching. Poster presented at: Muscular Dystrophy Association Clinical & Scientific Conference; March 16-19, 2025; Dallas, TX.