Drug Trials Snapshots: EXONDYS 51
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 EXONDYS 51 Prescribing Information for complete information.
EXONDYS 51 (eteplirsen)
(ex-ON-dys)
Serepta Inc.
Approval date: September 19, 2016
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
EXONDYS 51 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.
Duchenne muscular dystrophy is a rare disease that affects primarily boys. It is caused by a low level of one muscle protein (dystrophin). The lack of dystrophin causes progressive muscle weakness and premature death. This particular type of DMD disease affects about 13 percent of the population with DMD.
How is this drug used?
EXONDYS 51 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?
EXONDYS 51 increased dystrophin in the muscles of some patients. It is believed that this increase may predict clinical benefit in patients. More trials are ongoing to assess whether there is a clinical benefit.
What are the benefits of this drug (results of trials used to assess efficacy)?
In Trial 1 and 2, there was no evidence of a clinical benefit of EXONDYS 51 as assessed by 6 minute walk test.
In Trial 3, the primary endpoint was a change in dystrophin level. The table below presents individual patient dystrophin levels from Trial 3.
Table 2. Western Blot Results: EXONDYS 51-Treated (Week 48) vs Pre-treatment Baseline
(% Normal Dystrophin) (Trial 3)
| Patient Number | Baseline % normal dystrophin | Week 48 % normal dystrophin | Change from Baseline % normal dystrophin |
|---|---|---|---|
| 1 | 0.13 | 0.26 | 0.13 |
| 2 | 0.35 | 0.36 | 0.01 |
| 3 | 0.06 | 0.37 | 0.31 |
| 4 | 0.04 | 0.10 | 0.06 |
| 5 | 0.17 | 1.02 | 0.85 |
| 6 | 0.37 | 0.30 | -0.07 |
| 7 | 0.17 | 0.42 | 0.25 |
| 8 | 0.24 | 1.57 | 1.33 |
| 9 | 0.11 | 0.12 | 0.01 |
| 10 | 0.05 | 0.47 | 0.43 |
| 11 | 0.02 | 0.09 | 0.07 |
| 12 | 0.18 | 0.21 | 0.03 |
| Mean | 0.16 | 0.44 | 0.28; p=0.008 |
EXSONDYS 51 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 EXONDYS 51 was too small (12 patients, all boys) to determine if there were any differences in race and age subgroups.
All the patients in the trials were boys. There were insufficient numbers of patients to perform any subpopulation analyses.
What are the possible side effects?
The most common side effects are balance disorder and vomiting.
The table below summarizes adverse reactions that occurred in patients treated with EXONDYS 51 from Trial 1.
Table 3. Adverse Reactions in DMD Patients Treated with 30 or 50 mg/kg/week1 EXONDYS 51 with Incidence of at Least 25% More than Placebo (Trial 1)
| Adverse Reaction | EXONDYS 51 (N=8) % | Placebo (N=4) % |
|---|---|---|
| Balance disorder | 38 | 0 |
| Vomiting | 38 | 0 |
| Dermatitis contact | 25 | 0 |
150 mg/kg/week=1.67 times the recommended dosage
EXONDYS 51 Prescribing Information
Were there any differences in side effects among sex, race and age?
The trials that looked at the side effects of EXONDYS 51 were too small (12 patients, all boys) to determine if there were any differences in race and age subgroups.
All the patients in the trials were boys. There were insufficient numbers of patients to perform any subpopulation analyses.
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the clinical trials?
There were three clinical trials that enrolled patients with a particular type of Duchenne muscular dystrophy. The trials were conducted in the United States.
The figures below summarize, by sex, patients who enrolled in Trial 1 and 2 (Figure 1a), and Trial 3 (Figure 1b).
Figure 1a. Baseline Demographics by Sex (Trial 1 and 2)
Clinical trial data
Figure 1b. Baseline Demographics by Sex (Trial 3)
Clinical trial data
Figure 2a and Table 1a below summarize the percentage of patients by race in Trial 1 and 2.
Figure 2a. Baseline Demographics by Race (Trial 1 and 2)
Table 1a. Baseline Demographics by Race (Trial 1 and 2)
| Race | Number of Patients | Percentage |
|---|---|---|
| White | 11 | 92 |
| Asian | 1 | 8 |
| Black or African American | 0 | 0 |
Clinical trial data
Figure 2b and Table 1b below summarize the percentage of patients by race in Trial 3.
Figure 2b. Baseline Demographics by Race (Trial 3)
Table 1b. Baseline Demographics by Race (Trial 3)
| Race | Number of Patients | Percentage |
|---|---|---|
| White | 13 | 100 |
| Asian | 0 | 0 |
| Black or African American | 0 | 0 |
Clinical trial data
Figures 3a and 3b summarize the percentage of patients by age group in the Trials 1 and 2 and Trial 3, respectively.
Figure 3a. Baseline Demographics by Age (Trials 1 and 2)
Clinical trial data
Figure 3b. Baseline Demographics by Age (Trial 3)
Clinical trial data
The table below summarizes demographics of patients in the clinical trial.
Table 4. Baseline Demographics of Enrolled Patients in the Clinical Trials
| Demographic Parameters | Trial 1 and 2 N=12 n (%) | Trial 3 N=13 n (%) | |
|---|---|---|---|
| Sex | |||
| Male | 12 (100) | 13 (100) | |
| Age | |||
| Mean years | 8.8 | 8.9 | |
| Median (years) | 9 | 8 | |
| Min, max (years) | 7, 10 | 7, 13 | |
| Race | |||
| White | 11 (92) | 13 (100) | |
| Asian | 1 (8) | 0 | |
| Black or African American | 0 | 0 | |
| Region | |||
| Unites States | 12 (100) | 13 (100) | |
Clinical trial data
How were the trials designed?
There were three trials that evaluated the benefit and side effects of EXSONDYS 51.
In Trial 1, patients were randomly assigned to receive either EXONDYS 51 or placebo once a week for 24 weeks. 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 the distance a patient could walk on a flat, hard surface in a period of 6 minutes (called 6-minute walk test).
In Trial 2, all the patients from Trial 1 continued receiving EXONDYS 51 once a week for an additional 4 years. For comparison, FDA looked in the natural history data from Duchenne muscular dystrophy patient registries in Italy and Belgium. The benefit was evaluated by the 6-minute walk test.
In Trial 3, patients received EXONDYS 51 once a week for 48 weeks. The benefit of EXONDYS 51 was evaluated by measuring the level of dystrophin in muscle biopsies before and after 48 weeks of treatment.
The safety and efficacy of EXONDYS 51 were evaluated in three clinical trials. Enrolled patients had a genotypically confirmed DMD diagnosis (a confirmed mutation of the DMD gene that is amenable to exon 51 skipping). Patients were on a stable dose of corticosteroids for at least 6 months.
Trial 1 was a 24-week, randomized, placebo‑controlled, parallel-group trial. The primary clinical efficacy endpoint was the 6-minute walk test (6MWT).
Trial 2 was a 4 year, open-label extension of Trial 1. The primary clinical efficacy endpoint was 6MWT assessed in comparison to historical controls from 2 DMD patient registries.
Trial 3 was a 48-week open-label, baseline-control trial. The primary endpoint was a change in dystrophin level from muscle tissue before and after the treatment as assessed by Western blot.
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