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Drug Trials Snapshots: VYONDYS 53

HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race, and age 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 health provider about the risks and benefits of a drug. Refer to VYONDYS 53 Prescribing Information for complete information.

VYONDYS 53 (golodirsen)
vy-ON-dys
Serepta Therapeutics Inc.
Approval date: December 12, 2019


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

VYONDYS 53 is a drug for the treatment of a particular type of Duchenne muscular dystrophy (DMD). It is to be used only in patients who have a specific mutation of the dystrophin gene.

DMD is a rare disease that primarily affects boys. It is caused by low levels of a muscle protein called dystrophin. The lack of dystrophin causes progressive muscle weakness and premature death.

How is this drug used?

VYONDYS 53 is given by a health care professional once every week directly into the bloodstream through a needle in the vein. This is known as an intravenous, or IV infusion.

What are the benefits of this drug?

VYONDYS 53 increased levels of dystrophin in the muscles of most patients. It is believed that this increase may predict clinical benefit in patients.

VYONDYS 53 was approved under FDA’s accelerated approval program, which provides earlier patient access to a promising new drug while the company continues to conduct clinical trials to confirm that the drug works well.

More trials are ongoing to assess whether there is a clinical benefit of VYONDYS 53.

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

The table below presents individual patient dystrophin levels at baseline prior to treatment and at Week 48 of Part 2 from Trial 1.

Table 1. Dystrophin Expression by Individual Patient from Trial 1



Patient Number
Western Blot % Normal Dystrophin

Patient Number
Western Blot % Normal Dystrophin
Baseline Part 2 Week 48 Change from baseline Baseline Part 2 Week 48 Change from baseline
1 0.08 0.09 0.01 14 0.22 0.28 0.06
2 0.11 0.11 0.01 15 0.14 0.21 0.07
3 0.21 0.22 0.01 16 0.05 0.42 0.37
4 0.05 0.12 0.08 17 0.07 1.03 0.97
5 0.03 0.12 0.09 18 0.02 1.57 1.55
6 0.06 0.14 0.09 19 0.12 1.17 1.05
7 0.12 0.37 0.25 20 0.03 1.72 1.69
8 0.11 1.06 0.95 21 0.11 1.77 1.66
9 0.06 0.54 0.48 22 0.31 4.30 3.99
10 0.05 0.97 0.92 23 0.11 0.36 0.25
11 0.06 1.55 1.49 24 0.03 0.91 0.88
12 0.07 1.91 1.84 25 0.07 1.29 1.22
13 0.10 3.25 3.15        

VYONDYS 53 Prescribing Information

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

The trial that looked at the benefit of VYONDYS 53 consisted of boys only who were of similar age and predominantly White. It was not possible to determine if there were any differences in how well the drug worked in sex, race and age subgroups.

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

The population for this trial was both small and relatively homogeneous; therefore, no subpopulation efficacy analyses were conducted.

What are the possible side effects?

VYONDYS 53 may cause serious allergic reactions. Additionally, kidney damage was observed in animal studies.

The most common side effects of VYONDYS 53 are headache, fever, falling, abdominal pain, common cold, cough, vomiting, and nausea.

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

The table below summarizes adverse reactions that occurred in patients treated with VYONDYS 53 from Trials 1 and 2.

Table 2. Adverse Reactions That Occurred in At Least 20% of VYONDYS 53-Treated Patients and at a Rate Greater than Placebo in Trials 1 and 2

Adverse Reaction VYONDYS 53
(N = 41)
%
Placebo
(N = 21)
%
Headache 41 10
Pyrexia 41 14
Fall 29 19
Abdominal pain 27 10
Nasopharyngitis 27 14
Cough 27 19
Vomiting 27 19
Nausea 20 10

VYONDYS 53 Prescribing Information

Were there any differences in side effects among sex, race and age?

The trials that looked at the side effects of VYONDYS 53 consisted of boys only, who were of similar age and predominantly White. It was not possible to determine if there were any differences in side effects in sex, race and age subgroups.

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

The safety population consisted of boys, predominately White; therefore, no subpopulation analyses of side effects for sex and race were conducted. Limited analysis of age groups is presented below.

Table 3. Subgroup Analysis of TEAE by Age Group (safety population)

Adverse Event < 12 years
N=54
≥12 years
N=8
VYONDYS 53 Placebo VYONDYS 53 Placebo
Any TEAE 34/36 (94.4) 18/18 (100) 5/5(100) 2/3 (66.7)
Severe TEAE 2/36 (5.6) 0/18 (0) 4/5 (80) 1/3 (33.3)
Serious TEAE 4/36 (11.1) 0/18 (0) 1/5 (20) 1/3 (33.3)

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

There were two clinical trials that enrolled patients with DMD (Trial 1/NCT02310906 and Trial 2/NCT0250381). The trials were conducted in the United States and Europe.

Demographics of the combined populations from both trials that provided data for evaluation of side effects (called safety population) are presented below and in Table 4 under MORE INFO.

Only one part of Trial 1 provided data for evaluation of VYONDYS 53 benefits. Demographics of that population (called efficacy population) are presented in Table 5 under MORE INFO.

The figure below summarizes patients in combined Trials 1 and 2, by sex.

Figure 1. Baseline Demographics by Sex (safety population)

Pie chart summarizing how many men and women were in the clinical trial. In total, 62 men (100%) participated in the clinical trial.

Clinical Trial Data

Figure 2 summarizes the percentage of patients by race in Trials 1 and 2.

Figure 2. Baseline Demographics by Race (safety population)

Pie chart summarizing the percentage of patients by race enrolled in the clinical trial. In total,  White 53 (86%), 4 Asian (6%) and 5 Other (8%).

*Includes Black or African American, American Indian or Alaska Native and Other

Clinical Trial Data

Figure 3 summarizes the percentage of patients by age in Trials 1 and 2.

Figure 3. Baseline Demographics by Age (safety population)

Pie charts summarizing how many individuals of certain age groups were enrolled in the clinical trial. In total, 62 patients (100%) were 6-13 years

Clinical Trial Data

Who participated in the trials?

The table below summarizes demographics of patients in both clinical trials.

Table 4. Baseline Demographics of Enrolled Patients in the Clinical Trials (safety population)

Demographic Parameter VYONDYS 53
(N = 41)
n (%)
Placebo
(N = 21)
n (%)
Total
(N=62)
n (%)
Sex
Male 41 (100) 21(100) 62(100)
Race
White 35 (85.4) 18 (85.7) 53 (85.5)
Asian 3 (7.3) 1 (4.8) 4 (6.5)
Other 1 (2.4) 2 (9.5) 3 (4.8)
Black or African American 1 (2.4) 0 1 (1.6)
American Indian or Alaska Native 1 (2.4) 0 1(1.6)
Age (years)
Median (min, max) 8 (7,13) 8 (6,13) 8 (6,13)
Ethnicity
Hispanic or Latino 6 (14.6) 4 (19) 10 (16.1)
Not Hispanic or Latino 31 (75.6) 14 (66.7) 45 (72.6)
Not reported 4 (9.7) 3 (14.3) 7 (11.3)
Geographic Region
US 33 17 50 (80.6)
Europe 8 4 12 (19.4)

Clinical Trial Data

Table 5. Baseline Demographics of Patients in the Clinical Trial 1 (efficacy population)

  Total
N=25
n (%)
Sex
  Male 25 (100)
Race
  White 23 (92)
  Other 2 (8)
Age
  Median (years) 8
  Min, max (years) 6 - 13
Ethnicity
  Hispanic or Latino 4 (16)
  Not Hispanic or Latino 9 (36)
  Not Reported 12 (48)
Geographic Region
  US 1 (4)
  Europe 24 (96)

FDA Review

How were the trials designed?

There were two trials that evaluated VYONDYS 53 for DMD. Data from Trial 1 was used to evaluate the benefit and side effects of VYONDYS 53 and data from Trial 2 to evaluate side effects only. All patients were on a stable dose of corticosteroids for at least 6 months before entering the trials.

In Trial 1, patients were randomly assigned to receive either VYONDYS 53 or placebo once a week. Neither the patients nor the health care providers knew which treatment was being given until after the trial was completed. The benefit was evaluated by measuring the level of dystrophin in muscle biopsies before and after 48 weeks of treatment.

In Trial 2, patients received VYONDYS 53 or placebo once a week for up to 96 weeks. Neither the patients nor the health care providers knew which treatment was being given. Collected data was used for side effects assessment.

How were the trials designed?

The safety and efficacy of VYONDYS 53 were evaluated in two clinical trials. Enrolled patients had a genotypically confirmed DMD diagnosis (a confirmed mutation of the DMD gene that is amenable to exon 53 skipping). Patients were on a stable dose of corticosteroids for at least 6 months prior to enrollment.

Trial 1/Part 1 was a double-blind, placebo-controlled, dose-titration trial in 12 DMD patients. Patients were randomized 2:1 to receive VYONDYS 53 or matching placebo. Trial 1/Part 2 was a 168-week, open-label study assessing the efficacy and safety of VYONDYS 53 at a dose of 30 mg/kg/week in the 12 patients enrolled in Part 1, plus 13 additional treatment-naive patients with DMD amenable to exon 53 skipping. The primary efficacy endpoint was the change from baseline in the dystrophin protein level (measured as % of normal) at Week 48 of Part 2.

Trial 2 was a double-blind, placebo-controlled trial where patients received VYONDYS 53 at 30 mg/kg or placebo IV once weekly for up to 96 weeks, after which all patients received VYONDYS 53 at a dose of 30 mg/kg.

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 used in clinical trials 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.

PRESCRIBING INFORMATION

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