Drugs

Drug Trials Snapshots: ZEJULA

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 ZEJULA Prescribing Information for complete information.

ZEJULA (niraparib)
zuh-JOO-luh
Tesaro, Inc.
Approval date: March 27, 2017


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

ZEJULA is a drug used for the maintenance treatment of adult patients with recurrent ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. It is to be used in patients who have responded to their most recent platinum-based chemotherapy regimen with either complete or partial tumor shrinkage.

How is this drug used?

Three capsules (total of 300 mg) are taken once a day with or without food.

What are the benefits of this drug?

In the trial, women taking ZEJULA experienced a longer time period before their tumors worsened, in comparison to women who took placebo. Information on overall survival of these women is not available at this time.

What are the benefits of this drug (results of trials used to assess efficacy)?

The table below summarizes efficacy results for the clinical trial based on the Intent-To-Treat (ITT) population and presented by germline BRCA gene mutation status (gBRCAmut). Primary endpoint was Progression-Free Survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

Table 2. Efficacy Results - Trial 1 (IRC Assessmenta, Intent-To-Treat Population)

 gBRCAmut Cohortnon-gBRCAmut Cohort
ZEJULA
(N=138)
Placebo
(N=65)
ZEJULA
(N=234)
Placebo
(N=116)
PFS Median in months
(95% CI)
21.0
(12.9, NR)
5.5
(3.8, 7.2)
9.3
(7.2, 11.2)
3.9
(3.7, 5.5)
Hazard Ratio (HR)b
(95% CI)
0.26
(0.17, 0.41)
0.45
(0.34, 0.61)
p-valuec<0.0001<0.0001

a efficacy analysis was based on blinded central independent radiologic and clinical oncology review committee (IRC).
b based on a stratified Cox proportional hazards model
c based on a stratified log-rank test
NR=Not Reached
ZEJULA Prescribing Information

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

All the patients in the trial were women, therefore only race and age differences were analyzed.

  • Race: The majority of patients in the clinical trials were White. Differences in response to ZEJULA among races could not be determined.
  • Age: ZEJULA worked similarly in patients above and below 65 years of age.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

The table below summarizes efficacy results of IRC-PFS by age subgroup.

Table 3. Efficacy Analysis by Age Group

 ZEJULAPlaceboIRC-PFS HR
(95% CI)
n of events/
N of patients
Median
(months)
n of events/
N of patients
Median
(months)
gBRCAmut cohort
Age Group (years)
<6547/11015.532/497.20.32 (0.20, 0.51)
≥6511/28NR12/163.70.23 (0.10, 0.55)
Non-gBRCAmut cohort
Age Group (years)
<6575/1307.452/694.20.58 (0.40, 0.83)
≥6550/10411.136/473.80.40 (0.26, 0.62)

Adapted from FDA Review

What are the possible side effects?

ZEJULA may cause serious side effects including a bone marrow disorder (myelodysplastic syndrome), leukemia, and life-threatening high blood pressure.

Some of the most common side effects of ZEJULA are low blood cell counts (red, white and platelets), nausea, tiredness, constipation, vomiting, and stomach-area pain.

What are the possible side effects (results of trials used to assess safety)

The tables below summarize adverse reactions and electrolyte abnormalities in the clinical trial based on safety population defined as all patients who received at least one dose of the trial drug.

Table 4. Adverse Reactions Reported in ≥10% of Patients Receiving ZEJULA

 Grades 1-4*Grades 3-4*
 Zejula
N=367
%
Placebo
N=179
%
Zejula
N=367
%
Placebo
N=179
%
Blood and lymphatic system disorders
Thrombocytopenia615290.6
Anemia507250
Neutropenia306202
Leukopenia17850
Cardiac Disorders
Palpitations10200
Gastrointestinal Disorders
Nausea743531
Constipation40200.82
Vomiting341620.6
Abdominal pain/distention333922
Mucositis/stomatitis2060.50
Diarrhea20210.31
Dyspepsia181200
Dry mouth1040.30
General disorders and Administration Site Conditions
Fatigue/Asthenia574180.6
Metabolism and Nutrition Disorders
Decreased appetite25150.30.6
Infections and Infestations
Urinary tract infection1380.81
Investigations
AST/ ALT elevation10542
Musculoskeletal and Connective Tissue Disorders
Myalgia19200.80.6
Back pain18120.80
Arthralgia13150.30.6
Nervous system Disorders
Headache26110.30
Dizziness18800
Dysgeusia10400
Psychiatric Disorders
Insomnia2780.30
Anxiety1170.30.6
Respiratory, Thoracic, and Mediastinal Disorders
Nasopharyngitis231400
Dyspnea20811
Cough16500
Skin and Subcutaneous Tissue Disorders
Rash2190.50
Vascular Disorders
Hypertension20592

*CTCAE=Common Terminology Criteria for Adverse Events version 4.02
ZEJULA Prescribing Information

Table 5. Abnormal Laboratory Findings in ≥25% of Patients Receiving ZEJULA

 Grades 1-4Grades 3-4
 ZEJULA
N=367
(%)
Placebo
N= 179
(%)
ZEJULA
N= 367
(%)
Placebo
N= 179
(%)
Decrease in hemoglobin8556250.5
Decrease in platelet count7221350.5
Decrease in WBC count663770.7
Decrease in absolute neutrophil count5325212
Increase in AST362310
Increase in ALT281512

WBC=white blood cells; ALT=Alanine aminotransferase; AST=Aspartate aminotransferase
ZEJULA Prescribing Information

Were there any differences in side effects among sex, race and age?

All the patients in the trial were women, therefore only race and age differences were analyzed.

  • Race: The majority patients in the clinical trials were White. Differences in side effects among races could not be determined.
  • Age: The occurrence of side effect was similar between patients below and above 65 years of age.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

The table below summarizes adverse events Grade 1- 4 (G1-4) during the clinical trial by age subgroup.

Table 5. Subgroup Analysis of Adverse Events by Age Group

Common G1-4 Adverse
Events by Preferred Term
ZELUJA
n=367
Age <50
N= 55 (%)
Age 50- <65
N= 183 (%)
Age ≥ 65
N= 129 (%)
Anemia25 (45)92 (50)65 (50)
Thrombocytopenia33 (60)81 (44)85 (66)
Neutropenia18 (33)59 (32)34 (26)
Nausea41 (75)143 (78)86 (66)
Constipation19 (35)73 (40)57 (44)
Abdominal pain15 (27)77 (42)44 (34)
Vomiting23 (42)68 (37)35 (27)
Diarrhea15 (27)37 (20)19 (15)
Decreased appetite11 (20)39 (21)43 (33)
Fatigue/ Asthenia32 (58)116 (63)71 (55)
Headache18 (33)54 (30)28 (22)
Insomnia9 (16)49 (27)33 (26)
Anxiety2 (4)18 (10)11 (9)
Hypertension7 (13)53 (29)26 (20)

Adapted from FDA Clinical review

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The benefit and side effects of ZEJULA were evaluated based on evidence from 553 women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.

The trial was conducted in the USA, Canada, Europe, and Israel.

Figure 1 summarizes how many women were in the clinical trial.

Figure 1. Baseline Demographics by Sex

Pie chart summarizing how many women were in the clinical trial of the drug ZEJULA . In total, 5533 women (100%) participated in the clinical trial.

Adapted from FDA review

Figure 2 and Table 1 below summarize the percentage of patients by race in the clinical trial.

Figure 2. Baseline Demographics by Race

Pie chart summarizing the percentage of patients by race in clinical trial. In total, 480 Whites (87%), 19 Asians (3%), 7 Blak or African Americans (1%) and 47 Other (9%), participated in the clinical trial

Adapted from FDA review

Table 1. Baseline Demographics by Race

RaceNumber of Patients              Percentage
White48087
Asian193
Black or African American71
American Indian or Alaska Native1less than 1
 Unknown469

Adapted from FDA review

Figure 3 below summarizes the percentage of patients by age in the clinical trial.

Figure 3. Baseline Demographics by Age

Pie charts summarizing how many individuals of certain age groups were in the clinical trial. In total, 358 patients  were younger than 65 years (65%), and  195 patients were  65 years and older (35 %)

Adapted from FDA review

Who participated in the trials?

The table below summarizes demographics of patients in the clinical trial.

Table 6. Baseline Demographics of Patients in the Clinical Trial (ITT population)

DemographicgBRCAmut cohort
N= 203
Non-gBRCAmut cohort
N=350
 ZEJULA N=138
n(%)
Placebo N= 65
n(%)
ZEJULA N=234
n(%)
Placebo N=116
n(%)
Age (years)
Mean (SD)56.9 (9.3)57.2 (9.2)62 (9.4)59 (9.6)
Median57586360
Range36,8338, 7333, 8434, 82
Age Group (years)
18-64110 (80)49 (75)130 (56)69 (59)
≥ 6528 (20)16 (25)104 (44)47 (41)
≥ 754 (3)019 (8)16 (14)
Race
White123 (89)55 (84)201 (86)101 (87)
Black or African American1 (0.7)1 (2)4 (2)1 (1)
Asian2 (1.4)3 (6)10 (4)4 (3)
American Indian/ Alaska Native1 (0.7)000
Unknown11 (8)6 (8)19 (8)10 (9)
Geographic Region
US, Canada53 (38)28 (43)96 (41)44 (28)
Europe, Israel53 (38)28 (43)96 (41)44 (28)

Adapted from FDA review

How were the trials designed?

The benefit and side effects of ZEJULA were evaluated in one clinical trial of women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer. All patients had received at least two prior platinum regimens and had responded most recently (within 8 months) to a platinum-based therapy with either complete or partial tumor shrinkage.

Patients were tested with an FDA-approved test to determine whether they had a specific gene mutation, called a deleterious or germline BRCA mutation and then received either ZEJULA or placebo capsules once a day. Neither the patients nor the health care providers knew which treatment was being given until the trials were completed. The treatment continued until the disease progressed or the side effects became too toxic.

The benefit of ZEJULA was evaluated by measuring the duration of time in each group before the tumors worsened.

How were the trials designed?

There was one double-blind, placebo-controlled trial of women with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer within 8 weeks of the last therapy. All patients were in complete or partial response to their most recent platinum-based regimen and assigned to one of two cohorts based on the test results of the germline BRCA mutation.

The efficacy outcome measures was progression-free survival (PFS) assessed by the central independent radiologic and clinical oncology review committee (IRC) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

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

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Page Last Updated: 04/12/2017
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