Pivotal clinical trial
DUVYZAT was studied in EPIDYS, one of the largest, most inclusive, phase 3 DMD studies to date1,*
EPIDYS was a global, 18-month, double-blind, randomized, placebo-controlled trial that included patients with a broad range of genetic mutations.1,2
Ethan, an actual DUVYZAT patient for 4+ years.
Patients were:
- Ambulant boys aged ≥6 years with genetically confirmed DMD (median age of 9.8 years)2
- No restrictions on genetic mutations, but these were generally balanced across both groups1,2
- All patients completed two 4SC assessments with a mean of 8 seconds or less and were ambulatory and able to get up from the floor within 10 seconds1
- Patients were on a stable dose and regimen of corticosteroids, which was continued throughout the study1
Efficacy was assessed using multiple measures, including 4SC,† NSAA (including time-to-rise from the floor), VLFF, and a muscle strength assessment.1,2
Recruitment was prespecified in 2 groups:Baseline VLFF >5% but ≤30%1
(Efficacy and safety analysis group, n=120)
Composed of patients unlikely to lose mobility suddenly but expected to show measurable decline in function, strength, and fat fraction when on placebo.1
Baseline VLFF ≤5% or >30%1
(Safety analysis only, n=59)
Recruited to assess the safety of DUVYZAT in a broader population of patients with DMD.1
Ethan, an actual DUVYZAT patient for 4+ years.
PROTECTION against DMD progression with DUVYZAT1-3
DUVYZAT slowed functional decline by ~40% over 18 months as measured by 4SC
Significantly lower mean change from baseline vs placebo‡ using 4SC to measure muscle function (P=0.037)
Benefit of DUVYZAT over placebo was observed from week 481
Patients treated with DUVYZAT were able to complete 4SC faster than patients taking placebo2
Change in time to perform 4SC vs placebo‡
| DUVYZAT (n=81) | Placebo (n=39) | |
|---|---|---|
|
Mean baseline 4SC (seconds) |
3.39 |
3.48 |
|
Mean change from baseline |
1.25 |
3.03 |
|
Treatment difference from placebo (95% Cl) |
-1.78 |
|
|
P value |
0.037 |
|
| Mean baseline 4SC (seconds) | Mean change from baseline | Treatment difference from placebo (95% Cl) | P value | |
|---|---|---|---|---|
|
DUVYZAT (n=81) |
3.39 |
1.25 |
-1.78 |
0.037 |
|
Placebo (n=39) |
3.48 |
3.03 |
‡ DUVYZAT or placebo was administered in addition to a stable dose of corticosteroids throughout the study.2
Greater preservation of motor function vs placebo as shown by NSAA1,2,#
Fewer failed NSAA test items for patients on DUVYZAT vs placebo1,#,**
Loss of NSAA items at 18 months—target population5
% of patients with failure in NSAA items
# Nominally significant but not statistically significant based on the prespecified multiplicity adjustment.1
**
The NSAA is a DMD-specific assessment scale measuring lower limb function in ambulant children with DMD, comprising 17 items scored on a scale of 0 to 2.
A score of 2 indicates the activity is performed without difficulty; 1 indicates the activity is performed with some compensation; 0 indicates the activity cannot be performed independently.1,2,6
Slower decline and fewer failed test items across NSAA vs placebo1,2,#,**
Change from baseline in total NSAA item score over 18 months1
1.91
LESS DECLINE IN MOTOR FUNCTION
Treatment effect: 1.91 (0.30, 3.53)
-2.66 (-3.56, -1.76)
-4.58 (-5.89, -3.26)
DUVYZAT favored across multiple functional measures1
All patients were also receiving systemic corticosteroids in a dose and regimen that were to remain unchanged over the follow-up period.1
Less change in elbow flexion and knee extension over time1,‡‡
At baseline and at every visit, participants completed muscle strength assessment in the form of knee extension and elbow flexion by standardized, hand-held myometry.1
‡‡ Statistical significance was not achieved for knee extension or elbow flexion.
Compared with placebo at 18 months, DUVYZAT reduced new fat infiltration in key muscle groups required for ambulation2,7,§§
DUVYZAT reduced new fat infiltration
in the quadriceps and hamstrings7
MRS imaging showing VLFF increase from baseline after 18 months. The difference in fat fraction between the 2 groups is evident.7,||||
EOS, end of study; MRS, magnetic resonance spectroscopy.
§§ Nominally significant but not statistically significant based on the prespecified multiplicity adjustment.1
|||| MRS imaging from a single patient; may not be representative of all patients.
Changes in mean fat fraction over
18 months from baseline1,7
At 18 months, for the patients with VLFF baseline in the range of >5% to ≤30%, the mean increase (absolute difference from baseline levels) of VLFF was 7.48% in the DUVYZAT-treated patients compared to a 10.89% increase in patients who received placebo.2
PROTECTION with a well-characterized safety profile2
DUVYZAT safety was established across multiple clinical trials including 222 patients, many of whom were treated with DUVYZAT for more than 2 years.§
Adverse reactions reported in >5% of DUVYZAT-treated patients and at least 5% greater than placebo in the EPIDYS trial
| DUVYZAT n=118 % |
Placebo n=61 % |
|
|---|---|---|
| Diarrhea | 37 | 20 |
| Abdominal pain | 34 | 25 |
| ThrombocytopeniaII | 33 | 0 |
| Nausea/vomiting | 32 | 18 |
| Hypertriglyceridemia | 23 | 7 |
| Pyrexia | 13 | 8 |
| Myalgia | 9 | 3 |
| Rash | 9 | 2 |
| Arthralgia | 8 | 2 |
| Fatigue | 8 | 0 |
| Constipation | 7 | 2 |
| Decreased appetite | 7 | 0 |
§ Controlled and uncontrolled trials in patients with confirmed DMD aged 6 years and older treated with DUVYZAT, including 210 patients treated for ≥6 months, 187 patients for ≥12 months, and 105 patients for ≥24 months.2
II Thrombocytopenia includes platelet count decreased and thrombocytopenia.2
Diarrhea, the most common adverse reaction, usually occurred within the first few weeks of treatment and resolved with continued dosing.2,7
-
Majority of cases reported were classified as mild¶
- 3 patients experienced moderate diarrhea
- 1 patient experienced severe diarrhea
- 1 patient had interruption in treatment due to diarrhea
- No patients discontinued treatment due to diarrhea
Hypothyroidism and/or thyroid-stimulating hormone increase occurred in 5% of patients treated with DUVYZAT compared to 2% of patients on placebo.2
Thrombocytopenia occurred in 33% of patients treated with DUVYZAT compared to no patients on placebo.2
- Low platelet counts resulted in DUVYZAT dose reduction in 28% of patients
- The maximum decrease in platelets occurred within the first 2 months of therapy and remained low throughout the course of therapy
- In a few patients, thrombocytopenia was associated with bleeding events including epistaxis, hematoma, or contusions
In EPIDYS clinical trial, 2% of patients on DUVYZAT discontinued due to triglyceride levels >300 mg/dL.2
DUVYZAT reduced new fat infiltration in the quadriceps and hamstrings6
Changes in mean fat fraction over 18 months from baseline2
DUVYZAT reduced new fat infiltration in 5 key muscles important for ambulation2,7
- This suggests that DUVYZAT may slow muscle deterioration
References: 1. Mercuri E, Vilchez JJ, Boespflug-Tanguy O, et al; EPIDYS Study Group. Safety and efficacy of givinostat in boys with Duchenne muscular dystrophy (EPIDYS): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2024;23(4):393-403. 2. DUVYZAT. Prescribing information. ITF Therapeutics; 2024. 3. Mercuri EM, Brogna C, Zaidman CM, et al. Givinostat study in DMD: supportive results. Poster presented at: 2024 Muscular Dystrophy Association Clinical & Scientific Conference; March 3-5, 2024; Orlando, FL. 4. Data on file, ITF Therapeutics. 5. Mercuri E, Brogna C, Mah JK, et al. Givinostat in DMD: results of the Epidys study with particular attention to NSAA. Poster presented at: 2023 World Muscle Society Conference; October 2023; Charleston, SC. 6. Gupta V, Pitchforth JM, Domingos J, et al. Determining minimal clinically important differences in the North Star Ambulatory Assessment (NSAA) for patients with Duchenne muscular dystrophy. PLoS One. 2023;18(4):e0283669. 7. Vandenborne K. Givinostat in DMD: results of the Epidys study with particular attention to MR measures of muscle fat fraction. Oral presentation at Muscular Dystrophy Association Clinical & Scientific Conference; March 19-22, 2023; Dallas, TX, USA.