Drug Trials Snapshots: SKYCLARYS
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 SKYCLARYS 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).
SKYCLARYS (omaveloxolone)
skye klar' is
Reata Pharmaceuticals Inc.
Original Approval date: February 28, 2023
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
SKYCLARYS is a drug that treats adults and adolescent patients aged 16 years and older with Friedreich’s ataxia (FA).
FA is a rare, genetic disease that is caused by a defect in a gene called frataxin. This protein is essential for the functioning of the cells. Lack of this protein leads to balance issues, difficulty speaking, loss of motor skills leading to inability to walk, and heart failure leading to death.
How is this drug used?
SKYCLARYS is taken orally once daily on an empty stomach at least one hour before eating. SKYCLARYS capsules should be swallowed whole and should not be crushed or chewed.
Who participated in the clinical trials?
The FDA approved SKYCLARYS based on evidence from efficacy data from a single clinical trial (Study 1) of 103 patients 16 to 40 years of age with FA. The trial was conducted at 11 sites in the United States, Western Europe, and Australia.
The safety of SKYCLARYS was based on evidence from two trials including 165 patients with FA, including 137 patients exposed for at least 48 weeks, and 112 patients exposed for at least 96 weeks.
How were the trials designed?
The efficacy of SKYCLARYS was evaluated in a single clinical trial in 103 adult and adolescent patients with FA who were randomly assigned to received SKYCLARYS 150 mg or placebo for 48 weeks. Neither the patients nor the healthcare providers knew which treatment was being given. Patients with or without a foot deformity known as pes cavus that causes a high arch of the foot were included in the study. Pes cavus was defined as having a loss of lateral support and was determined if light from a flashlight could be seen under the patient’s arch when barefoot and weight bearing. The benefit was evaluated by measuring modified Friedreich’s Ataxia Rating Scale (mFARS) score and comparing the score to baseline with the score after 48 weeks in patients without pes cavus.
After the study was completed, all patients were entered into an extension study and continued to receive SKYCLARYS for over three years. Patients who remained in the study for three years were compared to similar patients who were untreated in a natural history study of patients with FA.
How were the trials designed?
The efficacy of SKYCLARYS was evaluated in a single trial. The trial was a 48-week, multicenter, randomized, double-blind, placebo-controlled study in patients 16 to 40 years of age with FA. A total of 103 patients were randomized (1:1) to receive SKYCLARYS 150 mg once daily (N=51) or placebo (N=52) for 48 weeks. Enrolled patients had to have a stable mFARS score between 20 and 80, be able to complete maximal exercise testing, and have a left ventricular ejection fraction of at least 40%. The prespecified primary analysis was the change from baseline in the mFARS score compared to placebo at Week 48 in the Full Analysis Population of patients without pes cavus (N=82). The mFARS is a clinical assessment tool to assess patient function, with a lower score on the mFARS signifying lesser physical impairment.
There was a post hoc, propensity-matched analysis that compared the mFARS scores in patients treated with SKYCLARYS after three years relative to a matched set of untreated patients from a natural history study. These exploratory analyses should be interpreted cautiously given the limitations of data collected outside of a controlled study.
DEMOGRAPHICS SNAPSHOT:
Figure 1 summarizes how many male and female patients were enrolled in Study 1 used to evaluate the efficacy of SKYCLARYS.
Figure 1. Baseline Demographics by Sex (Study 1 Safety Population)
Source: Adapted from FDA Review
Figure 2 summarizes the percentage of patients by race enrolled in the single clinical trial used to evaluate the efficacy of SKYCLARYS.
Figure 2. Baseline Demographics by Race (Study 1 Safety population)
Source: Adapted from FDA Review
Figure 3 summarizes how many patients by age were in the single trial used to evaluate the side effects of SKYCLARYS.
Figure 3. Baseline Demographics by Age (Study 1 Safety population)
Source: Adapted from FDA Review
Figure 4 summarizes how many patients by ethnicity were in the single trial used to evaluate the side effects of SKYCLARYS.
Figure 4. Baseline Demographics by Ethnicity (Study 1 Safety population)
Source: Adapted from FDA Review
Who participated in the trials?
Table 1 summarizes the demographics of patients who were randomized and dosed in Study 1 (Efficacy and Safety Population).
Table 1. Baseline Demographics of Patients in the Study 1 (Safety Population)
|
Demographic |
SKYCLARYS N=51 n (%) |
Placebo N=52 n (%) |
Total N=103 n (%) |
|
Age group, years |
|
|
|
|
<18 |
9 (18) |
15 (29) |
24 (23) |
|
≥18 |
42 (82) |
37 (71) |
79 (77) |
|
Sex |
|
|
|
|
Female |
31 (61) |
17 (33) |
48 (47) |
|
Male |
20 (39) |
35 (67) |
55 (53) |
|
Ethnicity |
|
|
|
|
Hispanic or Latino |
2 (4) |
3 (6) |
5 (5) |
|
Not Hispanic or Latino |
49 (96) |
49 (94) |
98 (95) |
|
Race |
|
|
|
|
White |
50 (98) |
50 (96) |
100 (97) |
|
Other |
1 (2) |
2 (4) |
3 (3) |
Source: Adapted from FDA Clinical Review
What are the benefits of this drug?
Patients treated with SKYCLARYS experienced less decline in function compared to placebo as measured by a neurological exam-based assessment that evaluates motor function, including the ability to swallow and speak, upper limb coordination, lower limb coordination, and upright stability.
What are the benefits of this drug (results of trials used to assess efficacy)?
The efficacy of SKYCLARYS was evaluated in a 48-week, randomized, double-blind, placebo-controlled study in patients 16 to 40 years of age with FA (Study 1). A total of 103 patients were randomized (1:1) to receive SKYCLARYS 150 mg once daily (N=51) or placebo (N=52). Patients with or without pes cavus (a foot deformity that causes a high arch) were included in Study 1. Pes cavus was determined if light from a flashlight could be seen under the patient’s arch when barefoot and weight bearing. The prespecified primary analysis was the change from baseline in the modified Friedreich’s ataxia rating scale (mFARS) score compared to placebo at Week 48 in patients without pes cavus. Lower scores indicate less impairment in function.
Treatment with SKYCLARYS resulted in statistically significant lower mFARS scores (less impairment) relative to placebo (see Table 2) at Week 48.
Table 2. mFARS Least Squares (LS) Mean Change From Baseline at Week 48
|
Parameter |
SKYCLARYS N=40 |
Placebo N=42 |
|
Mean (SD) baseline mFARS total score |
40.95 (10.39) |
38.78 (11.03) |
|
LS mean change from baseline at Week 48 |
-1.56 |
0.85 |
|
Treatment difference (95% CI) |
-2.41 (-4.32, -0.51) |
|
|
p-value |
0.0138 |
|
Source: SKYCLARYS Prescribing Information
Abbreviations: CI, confidence interval; LS, least square; mFARS, modified Friedreich’s Ataxia Rating Scale; SD, standard deviation
In a post hoc, propensity-matched analysis, lower mFARS scores were observed in patients treated with SKYCLARYS after three years relative to a matched set of untreated patients from a natural history study. These exploratory analyses should be interpreted cautiously given the limitations of data collected outside of a controlled study, which may be subject to confounding.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: The observed effect of SKYCLARYS appeared larger in males compared to females. Because of limited data, this difference may be due to chance.
- Race: The number of patients of races other than White was small; therefore, differences in how SKYCLARYS worked among races could not be determined.
- Age: The observed effect of SKYCLARYS was similar in patients in all age groups.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
In the Study 1 population, only 3% of the randomized patients were of races other than White, 53% of patients were male, and 23% were <18 years of age. Therefore, the power for detecting differential treatment effects by subgroup is limited due to the small numbers.
A difference by gender was observed in the primary efficacy analysis, change from baseline in mFARS scores; however, the observed difference is likely due to the small number of randomized males (N=55) and females (N=48) in the study population.
What are the possible side effects?
The most common adverse reactions experiences with SKYCLARYS were elevated liver enzymes, increase in cholesterol, headache, nausea, abdominal pain, fatigue, diarrhea, and musculoskeletal pain.
Maximum increases in liver enzymes occurred within 12 weeks after starting SKYCLARYS. Increases were generally not associated with any symptoms and were reversible following discontinuation of SKYCLARYS.
Increases in cholesterol were observed within two weeks of initiation of SKYCLARYS and returned to baseline within four weeks of discontinuing treatment.
Treatment with SKYCLARYS can cause an increase in B-type natriuretic peptide (BNP), a marker of cardiac function. Cardiac failure is common in patients with FA, and it is unclear if the increase in BNP is related to SKYCLARYS or the cardiac disease related to FA.
What are the possible side effects (results of trials used to assess safety)?
Table 3 shows the adverse reactions that occurred in 10% or more of patients treated with SKYCLARYS and greater than placebo.
Table 3. Adverse Reactions Reported in 10% or More of Patients Treated With SKYCLARYS and Greater Than Placebo
|
Adverse Reactions |
SKYCLARYS % |
Placebo % |
|
Elevated liver enzymes |
37 |
2 |
|
Headache |
37 |
25 |
|
Nausea |
33 |
13 |
|
Abdominal pain |
29 |
6 |
|
Fatigue |
24 |
14 |
|
Diarrhea |
20 |
10 |
|
Musculoskeletal pain |
20 |
15 |
|
Oropharyngeal pain |
18 |
6 |
|
Influenza |
16 |
6 |
|
Vomiting |
16 |
12 |
|
Muscle spasms |
14 |
6 |
|
Back pain |
13 |
8 |
|
Decreased appetite |
12 |
4 |
|
Rash |
10 |
4 |
Source: SKYCLARYS Prescribing Information
Were there any differences in side effects among sex, race, and age?
- Sex: The occurrence of side effects was similar in males and females.
- Race: The number of patients of races other than White was small; therefore, differences in the side effects of SKYCLARYS among races could not be determined.
- Age: The occurrence of side effects was similar in patients of all age groups.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Increases in liver enzymes and cholesterol were also observed in patients younger than 18 years of age but the magnitude of increase was lower in these patients.
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