Drug Trials Snapshots: ZILBRYSQ
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 ZILBRYSQ 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).
ZILBRYSQ (zilucoplan)
ZIL-brisk
UCB, Inc.
Original Approval date: October 17, 2023
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
ZILBRYSQ is a drug for the treatment of generalized myasthenia gravis (gMG) in adult patients. It is used by patients whose blood has antibodies against the acetylcholine receptor (AChR).
Myasthenia gravis is a rare disease that causes weakness in muscles, especially muscles that control the eyes, face, neck, mouth, swallowing, breathing, and limbs.
How is this drug used?
A healthcare provider, or after receiving proper training a patient or a caregiver, injects ZILBRYSQ underneath the skin of the lower right or left part of the abdomen, the upper outer arm, or thighs using a pre-filled syringe. This is known as subcutaneous injection.
ZILBRYSQ is given once daily. The amount of ZILBRYSQ depends on the patient’s body weight.
Who participated in the clinical trials?
The FDA approved ZILBRYSQ based on evidence from Study 1 in 174 adult patients with gMG whose blood had antibodies against AChR. The study was conducted at 68 sites in 10 countries including the United States, Canada, France, Germany, Italy, Japan, Norway, Poland, Spain, and the United Kingdom.
How were the trials designed?
The efficacy and safety of ZILBRYSQ were established in one multicenter, randomized, double-blind, placebo-controlled trial (Study 1). The study evaluated ZILBRYSQ for the treatment of gMG in adult patients whose blood had antibodies against AChR.
Patients were randomized to receive weight-tiered doses of ZILBRYSQ equivalent to 0.3 mg/kg or placebo subcutaneous injection once daily for 12 weeks.
The primary efficacy endpoint was the comparison of the change from baseline after 12 weeks of treatment on the Myasthenia Gravis Activities of Daily Living (MG-ADL) total score between patients treated with ZILBRYSQ and patients who received placebo in Study 1. MG-ADL is a scale reported by patients that assesses the impact of gMG on daily function.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female patients were enrolled in the clinical trial used to evaluate the efficacy of ZILBRYSQ.
Figure 1. Baseline Demographics by Sex
Source: Adapted from FDA Review
Figure 2 summarizes how many patients by race were enrolled in the trial used to evaluate the side effects of ZILBRYSQ.
Figure 2. Baseline Demographics by Race
Source: Adapted from FDA Review
Figure 3 summarizes how many patients by age were enrolled in the trial used to evaluate the efficacy of ZILBRYSQ.
Figure 3. Baseline Demographics by Age
Source: Adapted from FDA Review
Figure 4 summarizes how many patients by ethnicity were enrolled in the trial used to evaluate the efficacy of ZILBRYSQ.
Figure 4. Baseline Demographics by Ethnicity
Source: Adapted from FDA Review
Who participated in the trials?
Table 1 summarizes the demographic data for patients enrolled in Study 1 to evaluate the efficacy and safety of ZILBRYSQ.
Table 1. Baseline Demographic Characteristics
|
Demographic |
ZILBRYSQ |
Placebo |
Total |
|---|---|---|---|
|
Age group, years |
|||
|
18 to <65 |
64 (74.4) |
62 (70.5) |
126 (72.4) |
|
≥65 |
22(25.6) |
26 (29.5) |
48 (27.6) |
|
Sex |
|||
|
Female |
52 (60.5) |
47 (53.4) |
99 (56.9) |
|
Male |
34 (39.5) |
41 (46.6) |
75 (43.1) |
|
Race |
|||
|
American Indian or Alaska Native |
0 |
1 (1.1) |
1 (0.6) |
|
Asian |
7 (8.1) |
14 (15.9) |
21 (12.1) |
|
Black or African American |
6 (7.0) |
7 (8.0) |
13 (7.5) |
|
White |
66 (70.5) |
62 (76.7) |
128 (73.6) |
|
Missing |
7 (8.1) |
4 (4.5) |
11 (6.3) |
|
Ethnicity |
|||
|
Hispanic or Latino |
7 (8.1) |
5 (5.7) |
12 (7) |
|
Not Hispanic or Latino |
72 (83.7) |
79 (89.8) |
151 (87) |
|
Not reported |
1 (1.2) |
1 (1.1) |
2 (1.1) |
|
Unknown |
2 (2.3) |
0 |
2 (1.1) |
|
Missing |
4 (4.7) |
3 (3.4) |
7 (4) |
|
Region |
|||
|
East Asia |
7 (8.1) |
9 (10.2) |
16 (9.2) |
|
Europe |
34 (39.5) |
33 (37.5) |
67 (38.5) |
|
North America |
45 (52.3) |
46 (52.3) |
91 (52.3) |
Source: Adapted from FDA Review
What are the benefits of this drug?
The patients who received ZILBRYSQ experienced less weakness affecting their activities of daily living compared to those receiving placebo.
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 2 summarizes the efficacy results for the patients who were evaluated in Study 1. The primary outcome measure was the change from baseline to 12 weeks on the MG-ADL scale. The MG-ADL measures how patients feel about the effect of the disease on their daily activities. The total score ranges from 0 to 24. Higher scores represent greater severity of the disease.
Table 2. Change From Baseline in MG-ADL Total Score at Week 12 in Adults With gMG Who are Anti-AChR Antibody Positive in Study 1
|
MG-ADL Total Score |
ZILBRYSQ |
Placebo |
|---|---|---|
|
LS mean (95% CI) |
-4.4 (-5.3, -3.5) |
-2.3 (-3.2, -1.4) |
|
Difference from placebo (95% CI) |
-2.1 (-3.2, -0.9) |
|
|
p-value |
<0.001 |
|
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: ZILBRYSQ worked similarly in males and females.
- Race: The number of patients of races other than White was small; therefore, differences in how ZILBRYSQ worked among races could not be determined.
- Age: ZILBRYSQ worked similarly in patients younger and older than 65 years of age.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 3 summarizes the results of the subgroup analysis by sex and age. ZILBRYSQ worked similarly in males and females, and in patients younger and older than age 65 years. Differences in how well the drug worked among some racial groups could not be determined due to small number of patients enrolled in the study.
Table 3. Change From Baseline in MG-ADL Total Score at Week 12 in Adults With gMG Who are Anti-AChR Antibody Positive in Study 1
|
Demographic |
ZILBRYSQ |
Placebo |
Difference (95% CI) |
||
|---|---|---|---|---|---|
|
N |
LS Mean (95% CI) |
N |
LS Mean (95% CI) |
||
|
Sex |
|||||
|
Female |
52 |
-4.1 (-5.4, -2.9) |
47 |
-2.4 (-3.6, -1.1) |
-1.8 (-3.4, -0.1) |
|
Male |
34 |
-5.0 (-6.3, -3.7) |
41 |
-2.2 (-3.4, -1.0) |
-2.8 (-4.5, -1.1) |
|
Age group, years |
|||||
|
18 to <65 |
64 |
-4.3 (-5.4, -3.2) |
62 |
-2.1 (-3.2, -1.0) |
-2.2 (-3.7, -0.8) |
|
≥65 |
22 |
-4.4 (-6.1, -2.7) |
26 |
-2.4 (-4.0, -0.8) |
-2.0 (-3.9, -0.1) |
Source: Adapted from FDA Review
Abbreviations: AChR, acetylcholine receptor; CI, confidence interval; gMG, generalized myasthenia gravis; LS, least square; MG ADL, myasthenia gravis activities of daily living scale; NA, not applicable
What are the possible side effects?
ZILBRYSQ may increase the risk for infections. ZILBRYSQ may cause meningococcal meningitis. ZILBRYSQ is associated with pancreatitis and pancreatic cysts. The most common side effects of ZILBRYSQ are injection site reactions, upper respiratory tract infections, and diarrhea.
What are the possible side effects (results of trials used to assess safety)?
Table 4 summarizes the most common side effects of ZILBRYSQ that occurred in Study 1.
Table 4. Adverse Reactions in at least 5% of Patients Treated With ZILBRYSQ and More Frequently Than in Patients Who Received Placebo in Study 1
|
Adverse Reaction |
ZILBRYSQ |
Placebo |
|---|---|---|
|
Injection site reactions |
29 |
16 |
|
Upper respiratory tract infection |
14 |
7 |
|
Diarrhea |
11 |
2 |
|
Urinary tract infection |
8 |
5 |
|
Nausea or vomiting |
8 |
7 |
|
Lipase increased |
7 |
0 |
|
Amylase increased |
5 |
1 |
Source: ZILBRYSQ Prescribing Information
Were there any differences in side effects of the clinical trials 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 side effects among races could not be determined.
- Age: The number of patients aged 65 years and older was small; therefore, the differences in the side effects among age groups could not be determined.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 5 summarizes the results of the subgroup analysis by sex, age, and race. The majority of patients who received ZILBRYSQ in the study were female. Differences in side effects among some age and racial groups could not be determined due to the small number of patients enrolled in the study.
Table 5 . Side Effects Occurring in at Least 5% of Patients Treated With ZILBRYSQ and More Frequently Than in Patients Who Received Placebo in Study 1
|
Demographic |
ZILBRYSQ |
Placebo |
|---|---|---|
|
Sex |
||
|
Female |
45/52 (86) |
32/47 (68) |
|
Male |
21/34 (62) |
30/41 (73) |
|
Age group, years |
||
|
18 to <65 |
53/64 (83) |
47/62 (76) |
|
≥65 |
13/22 (59) |
15/26 (58) |
|
Race |
||
|
American Indian or Alaska Native |
0 (0) |
1/1 (100) |
|
Asian |
4/7 (57) |
9/14 (64) |
|
Black or African American |
4/6 (67) |
5/7 (71) |
|
White |
51/66 (77) |
43/62 (69) |
|
Missing |
7/7 (100) |
4/4 (100) |
|
Ethnicity, n (%) |
||
|
Hispanic or Latino |
3/7 (42.9) |
4/5 (80.0) |
|
Not Hispanic or Latino |
56/72 (77.8) |
54/79 (68.4) |
|
Not reported |
1/1 (100) |
1/1 (100) |
|
Unknown |
2/2 (100) |
0/0 (NA) |
|
Missing |
4/4 (100) |
3/3 (100) |
Source: Adapted from FDA Review
Abbreviation: N, number of patients in treatment arm; n, number of patients meeting criteria; NA, not applicable; Ns, total number of patients for each specific subgroup and were assigned to that specific arm
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 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.