Drug Trials Snapshots: DUVYZAT

HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.

LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.

Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the DUVYZAT Prescribing Information for all of the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).

Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).

DUVYZAT (givinostat)
doo' vi zat
Italfarmaco SpA
Original Approval date: March 21, 2024

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DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

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

How is this drug used?

DUVYZAT is taken by mouth twice daily with food. The dose is based on weight, and may be decreased, as needed, for certain side effects.

Who participated in the clinical trials?

The FDA approved DUVYZAT based on evidence from a single clinical trial of 179 male patients with DMD who were 6 years of age and older. The trial, Study 1, was conducted at 45 sites in 11 countries in North America and Europe. Twenty-eight of the patients were from the United States.

How were the trials designed?

DUVYZAT was evaluated in one randomized, placebo-controlled clinical trial of 179 male patients with DMD who could walk and were on stable background therapy with steroids.

How were the trials designed?

The effectiveness of DUVYZAT for the treatment of DMD was evaluated in a randomized, double-blind, placebo-controlled 18-month study. A total of 179 patients were randomized 2:1 to receive either DUVYZAT (n=118) or placebo (n=61). A weight-based dose regimen was applied. The study included male patients 6 years of age and older with a confirmed diagnosis of DMD who were ambulatory and on a stable dosage of corticosteroids. At baseline, patients had a mean age of 9.8 years, 90% were White, 3% were Asian, 3% were Black.

The primary analysis population (efficacy population, N=120) was based on a prespecified range of baseline muscle fat fraction as determined by magnetic resonance (MR) spectroscopy.

The primary endpoint was the change from baseline to Month 18 in 4-stair climb (4SC) time for DUVYZAT compared to placebo. The 4SC is a measure of muscle function that tests the time it takes to climb four stairs. A secondary efficacy endpoint was change from baseline to Month 18 in physical function as assessed by the North Star Ambulatory Assessment (NSAA). The primary analysis population was based on a prespecified range of baseline muscle fat fraction as determined by MR spectroscopy. Patients treated with DUVYZAT showed statistically significant less decline in the 4SC compared to placebo. Patients treated with DUVYZAT experienced less worsening on the NSAA compared to placebo, which was nominally significant but not statistically significant based on the prespecified multiplicity adjustment.

DEMOGRAPHICS SNAPSHOT

Figure 1 summarizes how many male and female patients were enrolled in the clinical trial used to evaluate the efficacy of DUVYZAT.

Figure 1. Baseline Demographics by Sex, Efficacy Population

Source: Adapted from FDA Review

Figure 2 summarizes how many patients by race were enrolled in the clinical trial used to evaluate the efficacy of DUVYZAT.

Figure 2. Baseline Demographics by Race, Efficacy Population

Source: Adapted from FDA Review

Figure 3 summarizes how many patients by age were enrolled in the clinical trial used to evaluate the efficacy of DUVYZAT.

Figure 3. Baseline Demographics by Age, Efficacy Population

Source: Adapted from FDA Review

Figure 4 summarizes how many patients by ethnicity were enrolled in the clinical trial used to evaluate the efficacy of DUVYZAT.

Figure 4. Baseline Demographics by Ethnicity, Efficacy Population

Source: Adapted from FDA Review

Who participated in the trials?

Table 1. Baseline Demographics, Efficacy Population

Characteristic	DUVYZAT N=81	Placebo N=39
Sex, n (%)
Male	81 (100)	39 (100)
Age, years
Mean (SD)	9.6 (2)	9.8 (2)
Median (min, max)	9.8 (6.3, 14.2)	9.6 (6.1, 13.5)
Age group, years, n (%)
Children (6 to <12)	72 (88.9)	32 (82.1)
Adolescent (≥12 to <18)	9 (11.1)	7 (17.9)
Race, n (%)
Asian	3 (3.7)	1 (2.6)
Black or African American	0	0
Other	4 (4.9)	2 (5.1)
White	74 (91.4)	36 (92.3)
Ethnicity, n (%)
Hispanic or Latino	6 (7.4)	3 (7.7)
Not Hispanic or Latino	75 (92.6)	36 (92.3)
Country of participation, n (%)
Canada	7 (8.6)	5 (12.8)
Germany	9 (11.1)	1 (2.6)
Spain	13 (16.0)	4 (10.3)
Italy	17 (21.0)	9 (23.1)
United States	17 (21.0)	11 (28.2)
Others	18 (22.2)	9 (23.1)
Is in United States, n (%)
United States	17 (21.0)	11 (28.2)
Non-United States	64 (79.0)	28 (71.8)

Source: Adapted from FDA Review
Abbreviations: SD, standard deviation

What are the benefits of this drug?

Clinical trial evidence from the single controlled study indicates that patients taking DUVYZAT showed less worsening in a test of muscle function than patients taking placebo.

The primary endpoint was the change from baseline to Month 18 in 4SC time for DUVYZAT compared to placebo. The 4SC is a measure of muscle function that tests the time it takes to climb four stairs. Patients taking DUVYZAT had better results on this test compared to those taking the placebo drug.

What are the benefits of this drug (results of trials used to assess efficacy)?

The primary endpoint was the change from baseline to Month 18 in 4SC time for DUVYZAT compared to placebo. A secondary efficacy endpoint was change from baseline to Month 18 in physical function as assessed by NSAA. Patients treated with DUVYZAT showed statistically significant less decline in the 4SC compared to placebo (mean change from baseline 1.25 for the DUVYZAT group and 3.03 for placebo, p-value 0.037). Patients treated with DUVYZAT experienced less worsening on the NSAA compared to placebo, which was nominally significant but not statistically significant based on the prespecified multiplicity adjustment.

Table 2. Change From Baseline to Month 18 on 4SC Compared to Placebo¹, Efficacy Population

Endpoint	DUVYZAT N=81	Placebo N=39
Mean baseline 4SC (seconds)	3.39	3.48
Mean change from baseline	1.25	3.03
Treatment difference (95% CI)	-1.78 (-3.46, -0.11)
p-value	0.037

Source: Adapted from DUVYZAT Prescribing Information
¹ DUVYZAT or placebo were administered in addition to a stable dose of corticosteroids throughout the study Abbreviations: 4SC, 4-stair climb; CI, confidence interval

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

• Sex: The study only included males because DMD is an X-linked recessive disease and female manifesting carriers are very rare. Therefore, differences in sex could not be determined.
• Race: Because almost all participants were White, differences between races in how DUVYZAT worked could not be determined.
• Age: DUVYZAT was tested in subjects ranging from 6 to 14 years of age at baseline, with a median of 9.7 years of age. Subgroup analyses suggest possible inconsistency in subgroups younger and older than 9.7 years of age, with trends toward less treatment effect in higher ages. However, the study was not powered to detect differences between age groups.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

Table 3. Subgroup Analyses for Primary Endpoint by Age Group, Efficacy Population

Age, Years	Treatment Group	Baseline Mean (SD)	Month 18 LS Mean 4SC (95% CI)	LS Mean Difference (95% CI)
≤9.7	DUVYZAT, n=40	3.72 (1.3)	3.96 (1.92, 6.00)	-3.62 (-6.82, -0.42)
	Placebo, n=20	3.90 (1.2)	7.58 (4.91, 10.24)
>9.7	DUVYZAT, n=41	3.06 (0.9)	4.58 (2.65, 6.51)	0.24 (-1.13, 1.61)
	Placebo, n=19	3.04 (1.0)	4.34 (2.23, 6.44)

Source: Adapted from FDA Review
Abbreviations: 4SC, 4-stair climb; CI, confidence interval; LS, least squares; SD, standard deviation

What are the possible side effects?

The most common adverse reactions (≥10% for DUVYZAT-treated patients) are diarrhea, abdominal pain, low platelets (thrombocytopenia), nausea or vomiting, increased triglycerides (hypertriglyceridemia), and fever. The label includes warnings for low platelets, elevated triglycerides, and diarrhea, for which the dose may need to be adjusted. DUVYZAT also carries a warning of possible QT prolongation.

See associated Medication Guide and IFU for instructions on how to take DUVYZAT and monitor for side effects.

What are the possible side effects (results of trials used to assess safety)?

Table 4. Adverse Reactions Reported in >5% of DUVYZAT-Treated Patients and at Least 5% Greater Than Placebo, Safety Population

Adverse Reaction	DUVYZAT N=118 %	Placebo N=61 %
Diarrhea	37	20
Abdominal pain	34	25
Thrombocytopenia1	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

Source: DUVYZAT Prescribing Information
¹ Thrombocytopenia includes platelet count decreased and thrombocytopenia

Were there any differences in side effects of the clinical trials among sex, race, and age?

• Sex: The study included only males because DMD is an X-linked recessive disease and female manifesting carriers are rare.
• Race: The majority of subjects were White, which makes it difficult to detect any differences among races in occurrence of side effects.
• Age: The occurrence of side effects was similar in patients younger and older than 12 years of age.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

Table 5. Side Effects by Sex, Race, Age, and Ethnicity, Safety Population

Characteristic	DUVYZAT N=118 n/Ns (%)	Placebo N=61 n/Ns (%)	Risk Difference % (95% CI)
Sex
Male	112/118 (94.9)	57/61 (93.4)	1.5 (‑5.9, 8.8)
Age group, years
Children (6 to <12)	95/100 (95.0)	45/49 (91.8)	3.2 (‑5.6, 11.9)
Adolescent (≥12 to <18)	17/18 (94.4)	12/12 (100)	‑5.6 (‑16.1, 5.0)
Race
Asian	4/4 (100)	2/2 (100)	0 (0, 0)
Black or African American	3/3 (100)	0/0 (NA)	NA
Other	5/5 (100)	2/2 (100)	0 (0, 0)
White	100/106 (94.3)	53/57 (93.0)	1.4 (‑6.6, 9.3)
Ethnicity
Hispanic or Latino	8/9 (88.9)	2/3 (66.7)	22.2 (‑34.9, 79.4)
Not Hispanic or Latino	104/109 (95.4)	55/58 (94.8)	0.6 (‑6.3, 7.5)

Source: Adapted from FDA Review
Abbreviations: CI, confidence interval; N, number of patients in treatment arm; n, number of patients with adverse event; NA, not applicable; Ns, total number of patients for each specific subgroup and were assigned to that specific arm

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.

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