Drugs Trials Snapshot: Oxlumo
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 the OXLUMO Prescribing Information for complete information.
OXLUMO (lumasiran)
(ox loo’ moe )
Alnylam Pharmaceuticals
Approval date: November 23, 2020
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
OXLUMO is a drug used to lower the level of urine oxalate in children and adults with primary hyperoxaluria type 1 (PH1).
PH1 is a rare, inherited disorder in which the liver makes too much oxalate. Excess oxalate can lead to kidney stones and kidney damage. Over time, oxalate can also build up in the body and damage other organs, including the heart, bones and eyes.
How is this drug used?
OXLUMO is an injection given under the skin (subcutaneously) once a month for the first three months. Some patients can then switch to an injection once every three months depending on their weight.
What are the benefits of this drug?
In one trial, patients treated with OXLUMO had a 65% decrease in urinary oxalate after 6 months of treatment compared with a 12% decrease in patients who received placebo. In a second trial, patients treated with OXLUMO had a decrease in urinary oxalate of 71%.
What are the benefits of this drug? (results of trials used to assess efficacy)?
The figures below summarize efficacy results for individual trials based on the percent reduction from baseline in 24 hour urinary oxalate excretion by month (Trial 1) or the percent reduction from baseline in the spot urinary oxalate:creatinine ratio by month (Trial 2).
Figure 5. Percent Change from Baseline in 24 hour Urinary Oxalate by Month (Trial 1)
Figure 6. Percent Change from Baseline in Spot Urinary Oxalate:Creatinine Ratio by Month-Trial 2
SEM = standard error of mean.
Results are plotted as mean (±SEM) of percent change from baseline.
OXLUMO Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
The trials that looked at the benefit of OXLUMO were too small to determine if there were differences among 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 following figure summarizes efficacy results by demographic subgroups in Trial 1. Efficacy findings appeared to be consistent across subgroups.
Figure 7. Subgroup Analysis of Trial 1
Lumasiran=OXLUMO BSA = body surface area; eGFR = estimated glomerular filtration rate; LS = least squares; N = number of patients in treatment group.
FDA Review
What are the possible side effects?
The most common side effects of OXLUMO are injection site reactions.
What are the possible side effects (result of trials used to assess safety)?
The table below summarizes adverse events in Trial 1.
Table 1. Adverse Reactions Reported in at Least 10% of Patients Treated with OXLUMO and that Occurred at Least 5% More Frequently than in Patients Treated with Placebo in Trial 1 During the 6 Month Double blind Period
|
Adverse Reaction |
OXLUMO |
Placebo |
|---|---|---|
|
Injection site reaction |
10 (38) |
0 (0) |
|
Abdominal pain* |
4 (15) |
1 (8) |
*Grouped term includes abdominal pain, abdominal pain upper, abdominal pain lower, and abdominal discomfort
OXLUMO Prescribing Information
Were there any differences in side effects among sex, race and age?
The trials that looked at the side effects of OXLUMO were too small to determine if there were differences among sex, race, and age subgroups.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
The following tables summarize adverse reactions by demographic subgroups from Trial 1. Given the small sample size for the subgroups, results must be interpreted with caution. Results by race are not shown because most patients enrolled in the trial were White.
Table 2. Analyses of Adverse Reactions by Sex
|
Adverse Reactions |
OXLUMO |
Placebo |
||
|---|---|---|---|---|
|
Male |
Female |
Male |
Female |
|
|
Injection site reaction# |
5 (28) |
5 (63) |
0 |
0 |
|
Abdominal pain* |
2 (11.1) |
2 (25.0) |
0 |
1 (20) |
Table 3. Analyses of Adverse Reactions by Age Group
|
Adverse Reactions |
OXLUMO |
Placebo |
||
|---|---|---|---|---|
|
6 to 17 years |
≥ 18 years |
6 to 17 years |
≥ 18 years |
|
|
Injection site reaction# |
3 (21) |
7 (58) |
0 |
0 |
|
Abdominal pain* |
3 (21) |
1 (8) |
1 (13) |
0 |
#Injection site reaction (grouped term) includes injection site reaction, Injection site erythema, injection site pain, and injection site discomfort.
*Abdominal pain (grouped term) includes abdominal pain, abdominal pain upper, abdominal pain lower, and abdominal discomfort.
Clinical Trial Data
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the trials?
The FDA approved OXLUMO based on two clinical trials (Trial 1/ NCT03681184 and Trial 2/ NCT03905694) of 55 patients with PH1. The trials were conducted at 25 centers in the United States, Europe, and the Middle East.
Figure 1 summarizes how many male and female patients were in the clinical trials.
Figure 1. Demographics by Sex (efficacy population)
Adapted from FDA Review
Figure 2 summarizes by race how many patients were in the clinical trials.
Figure 2. Demographics by Race (efficacy population)
Adapted from FDA Review
The figure below summarizes the age groups of patients in the clinical trials.
Figure 3. Demographics by Age (efficacy population)
Adapted from FDA Review
The figure below summarizes the patients by ethnicity in the clinical trials.
Figure 4. Demographics by Ethnicity (efficacy population)
Adapted from FDA Review
Who participated in the trials?
The table below summarizes demographics for the trials that supported the approval of OXLUMO.
Table 4. Trials Demographics (efficacy population)
|
Demographic Parameters |
Trial 1 |
Trial 2 |
TOTAL |
|---|---|---|---|
|
Sex, n (%) |
|||
|
Male |
26 (67) |
7 (44) |
33 (60) |
|
Female |
13 (33) |
9 (56) |
22 (40) |
|
Race, n (%) |
|||
|
White |
30 (77) |
14 (88) |
44 (80) |
|
Black or African American |
0 |
0 |
0 |
|
Asian |
6 (15) |
0 |
6 (11) |
|
Other |
3 (8) |
2 (12) |
5 (9) |
|
Age (years) |
|||
|
Median |
14.0 |
3.5 |
9.0 |
|
Min, max |
6.0, 60.0 |
0.2, 5.0 |
0.2, 60.0 |
|
Age Group, n (%) |
|||
|
<6 years |
0 |
16 (100) |
16 (29) |
|
6 -11 years |
16 (41) |
0 |
16 (29) |
|
≥12 - 17 years |
6 (15) |
0 |
6 (11) |
|
≥ 18 years |
17 (44) |
0 |
17 (31) |
|
Ethnicity , n (%) |
|||
|
Hispanic or Latino |
1 (3) |
1(6) |
2 (4) |
|
Not Hispanic or Latino |
38 (97) |
15 (94) |
53 (96) |
|
Region, n (%) |
|||
|
United States |
13 (33) |
1 (6) |
14 (25) |
|
Europe |
18 (46) |
8 (50) |
26 (47) |
|
Middle East |
8 (21) |
7 (44) |
15 (27) |
Adapted from FDA Review
How were the trials designed?
Trial 1 enrolled patients with PH1 who were 6 years of age or older. Patients randomly received either OXLUMO or placebo injections once a month for the first three months and then once every three months. Neither the patients nor the healthcare providers knew which treatment was being given until after the trial was completed. The benefit of OXLUMO was assessed by measuring the amount of oxalate in the urine over 24 hours and comparing it to placebo.
Trial 2 enrolled pediatric patients with PH1 who were younger than 6 years. All patients received OXLUMO for 6 months. The benefit of OXLUMO was assessed by measuring the amount of oxalate in a urine sample.
How were the trials designed?
OXLUMO was studied in two trials of patients with PH1.
Trial 1 was a randomized, double blind, placebo-controlled trial that enrolled patients 6 years of age and older with PH1 and an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2. Patients received 3 loading doses of 3 mg/kg OXLUMO or placebo administered once monthly followed by quarterly maintenance doses of 3 mg/kg OXLUMO or placebo. The primary endpoint was the percent reduction from baseline in 24 hour urinary oxalate excretion averaged over Months 3 through 6.
Trial 2 was a single arm trial in 16 patients <6 years of age with PH1 and an eGFR >45 mL/min/1.73 m2 for patients ≥12 months of age or a normal serum creatinine for patients <12 months of age. All patients received OXLUMO. The primary endpoint was the percent reduction from baseline in the spot urinary oxalate:creatinine ratio averaged over Months 3 through 6.
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.