Drug Trial Snapshot: GAMIFANT
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 GAMIFANT Prescribing Information for complete information.
GAMIFANT (emapalumab-lzsg)
gam’ i fant
Novimmune SA
Approval date:November 20, 2018
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
GAMIFANT is used to treat patients with primary hemophagocytic lymphohistiocytosis (HLH) who have been previously treated for the disease and whose disease
- has come back or progressed, or
- other medicines have not worked well enough or cannot be tolerated.
Primary HLH is an inherited form of HLH- a rare and life-threatening disorder. Patients with primary HLH have cells of the immune system called T and NK cells that don’t work properly causing too much inflammation.
How is this drug used?
GAMIFANT is an injection. It is given by a healthcare provider as an intravenous infusion (directly into blood stream) two times per week. It takes about 1 hour to receive GAMIFANT infusion.
What are the benefits of this drug?
After 8 weeks of treatment, sixty three percent of 27 patients achieved complete or partial improvement of HLH abnormalities.
What are the benefits of this drug (results of trials used to assess efficacy)?
The table below summarizes efficacy results established on the basis of overall response rate (ORR) at the end of treatment, defined as achievement of either a complete or partial response or HLH improvement. Efficacy was assessed in the population that received previous treatments for HLH.
Table 2. Overall Response Rate at End of Treatment
|
|
GAMIFANT |
|---|---|
|
Overall Response Rate |
|
|
N (%) |
17 (63) |
|
(95% CI) |
(0.42, 0.81) |
|
p-value† |
0.013 |
|
Overall Response by Category |
|
|
Complete response, n (%) |
7 (26) |
|
Partial response |
8 (30) |
|
HLH improvement |
2 (7.4) |
†p-value based on Exact Binomial Test at a one-sided significance level of 2.5% comparing proportion of patients with overall response to hypothesized null hypothesis of 40%.
CI = confidence interval
GAMIFANT Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: Differences in how well GAMIFANT worked between males and females could not be determined because of the small number of patients.
- Race: The majority of patients in the clinical trial were White. Differences among races could not be determined due to small number of patients of other races.
- Age: Differences in how well GAMIFANT worked among age groups could not be determined because of the small number of patients per group.
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 based on overall response rate (ORR) by sex, race and age. Because of the small sample size, these exploratory analyses should be interpreted with caution.
Table 3. Overall Response Rate by Baseline Demographics
|
Subgroups |
Sex |
Race |
Age |
||||
|---|---|---|---|---|---|---|---|
|
|
Female |
Male N=11 |
White |
Other N=10 |
0-6 months |
6-24 months N=10 |
>=2 years N=12 |
|
Overall response, n (%) |
9 (56) |
8 (73) |
13 (76) |
4 (40) |
2 (40) |
6 (60) |
9 (75) |
Adapted from Clinical Trial Data
What are the possible side effects?
GAMIFANT can cause serious infections and infusion-related allergic reactions.
The most common side effects of GAMIFANT are infections, high blood pressure, infusion-related reactions, and fever.
What are the possible side effects (results of trials used to assess safety)?
The table below summarize adverse reactions in the clinical trial. Presented is safety population which includes all patients who received at least one dose of GAMFIANT (all previously treated and treatment-naïve patients).
Table 4. Adverse Reactions Reported in ≥ 10% of Patients with Primary HLH
|
Adverse Reactions |
GAMIFANT (N = 34) |
|---|---|
|
Infectionsa |
56 |
|
Hypertensionb |
41 |
|
Infusion-related reactionsc |
27 |
|
Pyrexia |
24 |
|
Hypokalemia |
15 |
|
Constipation |
15 |
|
Rash |
12 |
|
Abdominal pain |
12 |
|
Cytomegalovirus infection |
12 |
|
Diarrhea |
12 |
|
Lymphocytosis |
12 |
|
Cough |
12 |
|
Irritability |
12 |
|
Tachycardia |
12 |
|
Tachypnea |
12 |
aIncludes viral, bacterial, fungal, and infections in which no pathogen was identified
bIncludes secondary hypertension
cIncludes events of drug eruption, pyrexia, rash, erythema, and hyperhidrosis
GAMIFANT Prescribing Information
Were there any differences in side effects among sex, race and age?
- Sex: Differences in the occurrence of side effects between males and females could not be determined because of the small number of patients.
- Race: The majority of patients in the clinical trial were White. Differences in side effects among races could not be determined due to small number of patients of other races.
- Age: Differences in occurrence of side effects among age groups could not be determined because of the small number of patients per group.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
The table below summarizes adverse events during the clinical trial by sex, race and age subgroups. Because of the small sample size, these exploratory analyses should be interpreted with caution.
Table 5. Subgroup Analysis of Treatment -Emerging Adverse Events
|
|
Sex |
Race |
Age |
||||
|---|---|---|---|---|---|---|---|
|
Males |
Females N=18 |
White |
Other |
0-6 months |
6-24 months |
>2 years |
|
|
Any TEAE, n (%) |
15 (93.8) |
17(94.4) |
21 (95.5) |
11 (91.7) |
8 (100) |
12 (92.3) |
12 (92.3) |
|
Infections, n (%) |
12 (75) |
7 (38.9) |
12 (54.5) |
7 (58.3) |
4 (50) |
8 (61.5) |
7 (53.8) |
Clinical Trial Data
WHO WAS IN THE STUDIES?
Who participated in the clinical trials?
The FDA approved GAMIFANT based on evidence from one clinical trial (NCT01818492) of 34 patients with primary HLH. The trial was conducted at 12 sites in the United States, Italy Spain and Germany.
Figure 1 summarizes how many males and females were in the clinical trial.
Figure 1. Baseline Demographics by Sex (safety population)
Clinical Trial Data
Figure 2 and Table 1 below summarize the percentage of patients by race in the clinical trial.
Figure 2. Baseline Demographics by Race (safety population)
Clinical Trial Data
Table 1. Baseline Demographics by Race
|
Race |
Number of Patients |
Percentage |
|---|---|---|
|
White |
22 |
64 |
|
Asian |
5 |
15 |
|
Black or African American |
3 |
9 |
|
Other |
4 |
12 |
Clinical Trial Data
Figure 3. Baseline Demographics by Age (safety population)
Clinical Trial Data
Who participated in the trials?
The table below summarizes demographics of safety population in the clinical trial.
Table 6. Baseline Demographics of Patients in the Clinical Trial-safety population
|
Parameter |
GAMIFANT |
|---|---|
|
Sex, n (%) |
|
|
Female |
18 (52.9) |
|
Male |
16 (47.1) |
|
Race, n (%) |
|
|
White |
22 (64.7) |
|
Asian |
5 (14.7) |
|
Black or African American |
3 (8.8) |
|
Other |
4 (11.8) |
|
Age at parental/family Informed Consent |
|
|
Mean (SD) |
2.24 (2.992) |
|
Median |
1.00 |
|
Min, Max |
0.1, 13.0 |
|
Age Group, n (%) |
|
|
< 2 years |
21 (61.8%) |
|
2 - < 12 years |
12 (35.3%) |
|
12 - < 18 years |
1 (2.9%) |
|
Ethnicity-Not reported |
|
|
Country of Origin |
|
|
US |
8 (23.5) |
|
Italy |
4 (11.8) |
|
Others |
16 (47.1) |
|
Missing |
6 (17.6) |
Clinical Trial Data
How were the trials designed?
There was one trial that evaluated benefit and side effects of GAMIFANT in patients with primary HLH. Most of the patients have received previous HLH treatments. GAMIFANT was administered two to three times a week for up to eight weeks.
The benefit of GAMIFANT was evaluated after 8 weeks of treatment by measuring normalization of all HLH abnormalities.
Following initial 8 weeks of treatment patients could continue treatment in the extension trial.
How were the trials designed?
The safety and efficacy of GAMIFANT were established in one trial of patients with primary HLH.
This was a multicenter, open-label, single-arm trial in pediatric patients with suspected or confirmed primary HLH with either refractory, recurrent, or progressive disease during conventional HLH therapy or who were intolerant of conventional HLH therapy. GAMIFANT was administrated vis intravenous infusion two to three times a week for up to eight weeks.
The primary endpoint was overall response rate (ORR), defined as the proportion of patients who achieved either a complete or partial response or HLH improvement. ORR was evaluated using an algorithm that included the following objective clinical and laboratory parameters: fever, splenomegaly, central nervous system symptoms, complete blood count, fibrinogen and/or D-dimer, ferritin, and soluble CD25 (also referred to as soluble interleukin-2 receptor) levels.
Safety was evaluated in 34 patients who received GAMIFANT. Safety population includes all previously treated patients (efficacy population) and 7 treatment naïve patients from the same trial.
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