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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

Taking DUVYZAT

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

4SC, 4-stair climb; DMD, Duchenne muscular dystrophy; NSAA, North Star Ambulatory Assessment; VLFF, vastus lateralis fat fraction.

* EPIDYS is an acronym for Epigenetic Rescue of Dystrophin Dysfunction trial.1

†The 4SC is a measure of muscle function that tests the time it takes to climb 4 stairs.

VIEW EPIDYS PIVOTAL TRIAL PUBLICATION
Taking DUVYZAT

Ethan, an actual DUVYZAT patient for 4+ years.

PRIMARY ENDPOINT

4SC

KEY SECONDARY ENDPOINTS

NSAA  | 
VLFF

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)

Tap & rotate Tap & Rotate PROTECTION against DMD progression with DUVYZAT
‡ DUVYZAT or placebo was administered in addition to a stable dose of corticosteroids throughout the study.2

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
(-3.46, -0.11)

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
(-3.46, -0.11)

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

DUVYZAT
Placebo
% 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

points
1.91 points down

LESS DECLINE IN MOTOR FUNCTION

Treatment effect: 1.91 (0.30, 3.53)

DUVYZAT (n=81)

-2.66 (-3.56, -1.76)

Placebo (n=39)

-4.58 (-5.89, -3.26)

DUVYZAT favored across multiple functional measures1

Tap & rotate Tap & Rotate
††

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

Zoom
Baseline
18 months
Patient taking placebo
Patient taking placebo baseline
Patient taking placebo 18 months
Patient taking DUVYZAT
Patient taking Duvyzat baseline
Patient taking Duvyzat 18 months
Baseline
18 months

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

Zoom
Baseline
VLFF%
18 mo (EOS)
Mean change from baseline (%, mean; 95% CI)

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

SEE THE FAT FRACTION DATA IN KEY MUSCLES

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

CTCAE, Common Terminology Criteria for Adverse Events.

Diarrhea was defined per CTCAE grade: mild=increase of <4 stools per day over baseline; moderate=increase of 4 to 6 stools per day over baseline; severe=increase of ≥7 stools per day over baseline.4

Significantly lower mean change from baseline vs placebo‡ using 4SC to measure muscle function (P=0.037)
DUVYZAT favored across multiple functional measures

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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.

Indication and Important Safety Information

DUVYZAT is a histone deacetylase inhibitor indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients 6 years of age and older.

Important Safety Information

Warnings and precautions

  • Hematological Changes: DUVYZAT can cause dose-related thrombocytopenia and other signs of myelosuppression, including anemia and neutropenia. Monitor platelets; dosage adjustment or discontinuation may be needed.
  • Increased Triglycerides: An increase in triglycerides can occur; dosage modification may be needed. Discontinuation may be needed.
  • Gastrointestinal Disturbances: Adjust dosage if moderate or severe diarrhea occurs. Antiemetics or antidiarrheal medications may be considered during treatment with DUVYZAT. Discontinue DUVYZAT if the symptoms persist.
  • QTc Prolongation: Avoid use of DUVYZAT in patients who are at an increased risk for ventricular arrhythmias.

Indication

DUVYZAT is a histone deacetylase inhibitor indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients 6 years of age and older.

Important Safety Information

Warnings and precautions

  • Hematological Changes: DUVYZAT can cause dose-related thrombocytopenia and other signs of myelosuppression, including anemia and neutropenia. Monitor platelets; dosage adjustment or discontinuation may be needed.
  • Increased Triglycerides: An increase in triglycerides can occur; dosage modification may be needed. Discontinuation may be needed.
  • Gastrointestinal Disturbances: Adjust dosage if moderate or severe diarrhea occurs. Antiemetics or antidiarrheal medications may be considered during treatment with DUVYZAT. Discontinue DUVYZAT if the symptoms persist.
  • QTc Prolongation: Avoid use of DUVYZAT in patients who are at an increased risk for ventricular arrhythmias.

Recommended Evaluation and Testing Before Initiation of DUVYZAT:

Obtain and evaluate baseline platelet counts and triglycerides prior to initiation of DUVYZAT. Do not initiate DUVYZAT in patients with a platelet count less than 150 x 109/L. Monitor platelet counts and triglycerides as recommended during treatment to determine if dosage modifications are needed.

In addition, in patients with underlying cardiac disease or taking concomitant medications that cause QT prolongation, obtain ECGs when initiating treatment with DUVYZAT, during concomitant use, and as clinically indicated.

Most Common Adverse Reactions:

Most common adverse reactions (≥10% in DUVYZAT-treated patients) are diarrhea, abdominal pain, thrombocytopenia, nausea/vomiting, hypertriglyceridemia, and pyrexia.

To report SUSPECTED ADVERSE REACTIONS, contact ITF Therapeutics LLC at 1-833-582-4312 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full Prescribing Information and Medication Guide.