Drug Trials Snapshots: FILSPARI
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.
SSome 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 FILSPARI Prescribing Information for all 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).
FILSPARI (sparsentan)
fil spah' ree
Travere Therapeutics, Inc.
Approval date: February 17, 2023 (Accelerated Approval)
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
FILSPARI is an endothelin type A receptor and angiotensin II type 1 receptor antagonist that is indicated to reduce proteinuria in adults with primary immunoglobulin A (IgA) nephropathy at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) ≥1.5 g/g.
How is this drug used?
FILSPARI is an oral tablet that is taken once daily.
Who participated in the clinical trials?
FDA granted accelerated approved to FILSPARI based on evidence from a clinical trial (PROTECT) of patients with IgA nephropathy. The trial was conducted at 156 sites in 18 countries in North America, Europe, and Asia-Pacific. The same trial was used to assess both efficacy and safety. The efficacy analyses were based on an interim analysis of 281 patients (141 on FILSPARI, 140 on irbesartan) who reached Week 36 in the trial. The safety analyses were based on 404 patients (202 each on FILSPARI and irbesartan) who received at least one dose of either drug.
How were the trials designed?
FILSPARI was evaluated in a randomized, double-blind, active-controlled, clinical trial (PROTECT) in patients with IgA nephropathy. Patients with IgA nephropathy and protein in the urine were randomly assigned to receive either FILSPARI or irbesartan once daily. The primary endpoint for accelerated approval was the mean change in urine protein at Week 36 compared to baseline.
How were the trials designed?
FILSPARI was evaluated in a multicenter, double-blind, randomized, active-controlled study (PROTECT/NCT03762850). Patients with IgA nephropathy, eGFR (a measure of kidney function) ≥30 mL/min/1.73 m2, and total urine protein ≥1.0 g/day on a maximized stable dose of renin-angiotensin system (RAS) inhibitor treatment were enrolled. Patients with other glomerulopathies or those who had been recently treated with systemic immunosuppressants were excluded. Patients were randomized 1:1 to either FILSPARI (400 mg once daily following 200 mg once daily for 14 days) or irbesartan (300 mg once daily following 150 mg once daily for 14 days) and treated for 36 weeks. Rescue immunosuppressive therapy was allowed during the trial but sodium-glucose cotransporter-2 (SGLT2) inhibitors were not allowed. The primary endpoint was the relative change from baseline in UPCR (the amount of protein in the urine) at Week 36.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many males and females were enrolled in the clinical trial used to evaluate the efficacy of FILSPARI.
Figure 1. Baseline Demographics by Sex (Interim Analysis Set)
Source: Adapted from FDA Review
Figure 2 summarizes the percentage of patients by race enrolled in the clinical trial used to evaluate the efficacy of FILSPARI.
Figure 2. Baseline Demographics by Race (Interim Analysis Set)
Source: Adapted from FDA Review
Figure 3 summarizes the percentage of patients by age enrolled in the clinical trial used to evaluate the efficacy of FILSPARI.
Figure 3. Baseline Demographics by Age (Interim Analysis Set)
Source: Adapted from FDA Review
Figure 4 summarizes the percentage of patients by ethnicity enrolled in the clinical trial used to evaluate the efficacy of FILSPARI.
Figure 4. Baseline Demographics by Ethnicity (Interim Analysis Set)
Source: Adapted from FDA Review
Who participated in the trials?
Table 1 summarizes demographics for patients in the clinical trial.
Table 1. Baseline Demographics, Study PROTECT, IAS
| Demographic |
FILSPARI |
Irbesartan |
Total |
|
Sex, n (%) |
|
|
|
|
Female |
50 (35.5) |
37 (26.4) |
87 (31.0) |
|
Male |
91 (64.5) |
103 (73.6) |
194 (69.0) |
|
Age, years |
|
|
|
|
Mean (SD) |
46.8 (13.08) |
45.5 (11.75) |
46.1 (12.43) |
|
Median |
48.0 |
45.0 |
46.0 |
|
IQR |
38.0, 57.0 |
36.5, 54.5 |
37.0, 56.0 |
|
Min, max |
18.0, 73.0 |
19.0, 76.0 |
18.0, 76.0 |
|
Age group, years, n (%) |
|
|
|
|
≤45 |
67 (47.5) |
72 (51.4) |
139 (49.5) |
|
>45 |
74 (52.5) |
68 (48.6) |
142 (50.5) |
|
Race, n (%) |
|
|
|
|
Asian |
59 (41.8) |
38 (27.1) |
97 (34.5) |
|
Black or African American |
1 (<1) |
3 (2.1) |
4 (1.4) |
|
White |
79 (56.0) |
94 (67.1) |
173 (61.6) |
|
Other |
2 (1.4) |
5 (3.6) |
7 (2.5) |
|
Ethnicity, n (%) |
|
|
|
|
Hispanic or Latino |
10 (7.1) |
9 (6.4) |
19 (6.8) |
|
Not Hispanic or Latino |
131 (92.9) |
128 (91.4) |
259 (92.2) |
|
Not reported |
0 |
3 (2.1) |
3 (1.1) |
Source: Adapted from FDA Review
Abbreviations: IAS, interim analysis set; IQR, interquartile range; SD, standard deviation
What are the benefits of this drug?
A trial comparing FILSPARI to irbesartan (a drug that blocks the angiotensin II type 1 receptor) evaluated the mean reduction in protein in the urine compared to baseline after 36 weeks of treatment. Compared to baseline, there was a 45% reduction in the mean urine protein for FILSPARI compared to a 15% reduction for irbesartan.
FILSPARI 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.
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 2 summarizes the efficacy results of the trial.
Table 2. Efficacy Analyses (PROTECT Study), IAS
| Endpoint |
FILSPARI N=141 |
Irbesartan N=140 |
|
Adjusted GM of UPCR1, g/g |
|
|
|
Baseline |
1.2 (n=141) |
1.2 (n=140) |
|
Week 36 |
0.7 (n=135) |
1.0 (n=128) |
|
Adjusted GMPC from baseline in UPCR at Week 36 (95% CI) |
-45% (-51, -38) |
-15% (-24, -4) |
|
FILSPARI versus Irbesartan: Ratio of adjusted GM relative to baseline at Week 36 (95% CI) |
0.65 (0.55, 0.77) |
|
|
p-value |
<0.0001 |
|
Source: FILSPARI Prescribing Information
1 Adjusted GM of UPCR was based on MMRM stratified by screening eGFR and total urine protein excretion. MMRM analysis includes UPCR data during the double-blind period up to Week 36 from the first 281 randomized and treated subjects at the interim analysis. Baseline was defined as the last non-missing observation on or prior to the start of dosing.
Missing data were imputed using multiple imputation under the missing at random assumption. Data observed while on randomized treatment and after treatment discontinuation were included in the analysis regardless of treatment discontinuation and initiation of rescue therapy (treatment policy strategy). Rescue immunosuppressive treatment was initiated in 1.4% and 5.7% of FILSPARI and irbesartan patients, respectively.
Abbreviations: CI, confidence interval; eGFR, estimated glomerular filtration rate; GM, geometric mean; GMPC, geometric mean percent change; IAS, interim analysis set; MMRM, mixed model repeated measures; N, number of subjects in each group; n, number of subjects with available data at the time of analysis; UPCR, urine protein-to-creatinine ratio
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: FILSPARI worked similarly in males and females.
- Race: FILSPARI worked similarly in Whites and Asians. The number of patients of other races was small; therefore, differences in how FILSPARI worked in those races could not be determined.
- Age: FILSPARI worked similarly in patients younger and older than 45 years of age.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 3. Subgroup Analysis: Geometric Mean Ratio of Urine Protein to Creatinine Ratio at Week 36 Relative to Baseline in Efficacy Trial
|
Demographic |
Ratio of GM Relative to Baseline at Week 36 (FILSPARI vs. Irbesartan) |
95% CI |
|
Sex |
|
|
|
Male |
0.65 |
0.47, 0.84 |
|
Female |
0.70 |
0.44, 0.95 |
|
Race |
|
|
|
White |
0.67 |
0.47, 0.86 |
|
Asian |
0.69 |
0.46, 0.92 |
|
Age group, years |
|
|
|
≤45 |
0.69 |
0.47, 0.92 |
|
>45 |
0.62 |
0.42, 0.82 |
Source: Adapted from FDA Review
Note: Ratios and credible intervals include the relevance of outcomes from other subgroups.
Abbreviations: CI, confidence interval; GM, geometric mean
What are the possible side effects?
FILSPARI is available only through a restricted program called the FILSPARI Risk Mitigation and Evaluation Strategy (REMS). Under the FILSPARI REMS, prescribers, patients, and pharmacies must enroll in the program.
FILSPARI can cause changes in liver tests. Some medicines that are like FILSPARI can cause liver failure. Patients should undergo testing to monitor their liver before starting FILSPARI, then monthly for the first 12 months, and then every 3 months during treatment with FILSPARI.
FILSPARI can cause serious birth defects if taken during pregnancy and should not be started in someone who is pregnant. Patients who can become pregnant should undergo pregnancy testing prior to starting FILSPARI, monthly during treatment with FILSPARI, and one month after stopping treatment with FILSPARI.
Other potential risks of FILSPARI include low blood pressure, injury to the kidney, high potassium in the blood, and fluid retention.
In the PROTECT study, the most common side effects with FILSPARI were swelling of the extremities, low blood pressure, dizziness, high blood potassium, anemia, injury to the kidney, and increased liver enzymes in the blood.
What are the possible side effects (results of trials used to assess safety)?
Table 4 summarizes common adverse reactions that occurred in ≥2% of patients treated with FILSPARI.
Table 4. Adverse Reactions1 Reported in ≥2% of Subjects Treated With FILSPARI
|
Adverse Reaction |
FILSPARI N=202 n (%) |
Irbesartan N=202 n (%) |
|
Peripheral edema |
29 (14) |
19 (9) |
|
Hypotension (including orthostatic hypotension) |
28 (14) |
12 (6) |
|
Dizziness |
27 (13) |
11 (5) |
|
Hyperkalemia |
27 (13) |
21 (10) |
|
Anemia |
10 (5) |
5 (2) |
|
Acute kidney injury |
9 (4) |
2 (1) |
|
Transaminase elevations2 |
5 (2.5) |
4 (2) |
Source: FILSPARI Prescribing Information
1 Data presented include all treatment-emergent adverse events reported
2 Elevations in ALT or AST >3-fold ULN reported as adverse events of interest
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ULN, upper limit of normal
Were there any differences in side effects among sex, race and age?
- Sex: The occurrence of side effects with FILSPARI was similar in males or females.
- Race: The occurrence of side effects with FILSAPRI was similar in Whites or Asians. The number of patients of races other than White or Asian was small; therefore, differences in side effects for other races could not be determined.
- Age: The occurrence of side effects with FILSAPRI was similar in patients younger and older than 45 years of age.
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.
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