Drug Trials Snapshots: TAKHZYRO
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 TAKHZYRO Package Insert for complete information.
TAKHZYRO (lanadelumab-flyo)
tak-ZYE-roe
Dyax Corp.
Approval date: August 23,2018
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
TAKHZYRO is a drug used to prevent attacks of hereditary angioedema in people 12 years and older.
Hereditary angioedema is a rare, inherited and sometimes life-threatening condition with repeat episodes (attacks) of severe swelling in various parts of the body, including stomach, limbs, face and throat.
How is this drug used?
TAKHZYRO is injected under the skin every two weeks.
What are the benefits of this drug?
Patients who received TAKHZYRO had fewer angioedema attacks compared to those receiving the placebo.
What are the benefits of this drug (results of trials used to assess efficacy)?
The table below summarizes efficacy results for the evaluated patients for Trial 1. The main trial endpoint was investigator-confirmed mean hereditary angioedema (HAE) attack rate during the 26-week treatment period (Day 0 through 182).
Table 2. Results of Primary Efficacy Measures- Intent-to-Treat (ITT) Population
| Endpoint Statistics | Placebo (N=41) | TAKHZYRO | ||
|---|---|---|---|---|
| 150mg q4wks (N=28) | 300 mg q4wks (N=29) | 300 mg q2wks (N=27) | ||
| Number of HAE Attacks from Day 0 to 182a | ||||
| LS Mean (95% CI) monthly attack rateb | 1.97 (1.64, 2.36) | 0.48 (0.31, 0.73) | 0.53 (0.36, 0.77) | 0.26 (0.14, 0.46) |
| % Reduction relative to placebo (95% CI)c | 76 (61, 85) | 73 (59, 82) | 87 (76, 93) | |
| Adjusted p-valuesd | > | > | > | |
CI=confidence interval; SD=standard deviation; LS=least squares.
Note: Results are from a Poisson regression model accounting for over dispersion with fixed effects for treatment group (categorical) and normalized baseline attack rate (continuous), and the logarithm of time in days each patient was observed during the treatment period as an offset variable in the model.
aPrimary efficacy endpoint.
bModel-based treatment period HAE attack rate (attacks/4 weeks).
cCalculated as the ratio of the model-based treatment period HAE attack rates (TAKHZYRO/placebo) minus 1 multiplied by 100.
dAdjusted p-values for multiple testing.
TAKHZYRO Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: TAKHZYRO worked similarly in males and females.
- Race: The majority of patients was White. The number of patients of other races was limited; therefore, differences in response among races could not be determined.
- Age: The majority of patients was less than 65 years of age. The number of patients 65 years and older was limited; therefore, differences in response among age groups could not be determined.
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 by sex, race, and age.
Table 3. HAE Attack Rates by Sex, Race, and Age
| Placebo | TAKHZYRO 150mg q4wks | TAKHZYRO 300mg q4wks | TAKHZYRO 300mg q2wks | |||||
|---|---|---|---|---|---|---|---|---|
| n | LSM (95% CI) | n | LSM (95% CI) | n | LSM (95% CI) | n | LSM (95% CI) | |
| Sex | ||||||||
| Male | 7 | 2.2 (1.4-3.5) | 8 | 0.6 (0.3-1.3) | 10 | 0.4 (0.2-0.9) | 12 | 0.2 (0.1-0.6) |
| Female | 34 | 1.9 (1.6-2.4) | 20 | 0.4 (0.2-0.7) | 19 | 0.6 (0.4-0.9) | 15 | 0.3 (0.1-0.6) |
| Race | ||||||||
| White | 39 | 2.0 (1.7-2.4) | 25 | 0.4 (0.2-0.6) | 23 | 0.5 (0.3-0.8) | 26 | 0.3 (0.2-0.5) |
| Other | 2 | 1.1 (0.4-2.7) | 3 | 1.3 (0.7-2.3) | 6 | 0.5 (0.3-1.0) | 1 | NE |
| Age Group (years) | ||||||||
| Age: > | 4 | 0.5 (0.2-1.2) | 1 | NE | 3 | 0.4 (0.1-1.4) | 2 | 0.2 ((0.1-0.8) |
| 18-40 | 14 | 1.7 (1.3-2.3) | 9 | 0.7 (0.4-1.1) | 10 | 0.3 (0.2-0.7) | 12 | 0.3 (0.1-0.5) |
| 41-65 | 21 | 2.4 (1.9-3.0) | 15 | 0.3 (0.2-0.6) | 16 | 0.7 (0.4-1.1) | 13 | 0.2 (0.1-0.6) |
| >65 | 2 | 24.6 (8.1-74.1) | 3 | 0.1 (0.1-0.5) | 0 | 0 | ||
LSM: Least Squares Mean
CI: Confidence Interval
NE: Not Estimable
Clinical Trial Data
What are the possible side effects?
TAKHZYRO may cause serious allergic reactions.
The most common side effects of TAKHZYRO are injection site reactions, upper respiratory infections, headache, rash, muscle pain, dizziness, and diarrhea.
What are the possible side effects (results of trials used to assess safety)?
The table below summarizes adverse reactions in patients with hereditary angioedema (Trial 1).
Table 4. Adverse Reactions Observed in ≥10% of Patients Treated with TAKHZYRO in Trial 1
| Adverse Reaction | TAKHZYRO | ||||
|---|---|---|---|---|---|
| Placebo (N = 41) | 150 mg q4wks (N=28) | 300 mg q4wks (N=29) | 300 mg q2wks (N=27) | Total (N=84) | |
| n (%) | n (%) | n (%) | n (%) | n (%) | |
| Injection site reactionsa | 14 (34) | 16 (57) | 13 (45) | 15 (56) | 44 (52) |
| Upper respiratory infectionb | 13 (32) | 3 (11) | 9 (31) | 12 (44) | 24 (29) |
| Headachec | 9 (22) | 3 (11) | 6 (21) | 9 (33) | 18 (21) |
| Rashd | 2 (5) | 2 (7) | 3 (10) | 1 (4) | 6 (7) |
| Myalgia | 0 | 1 (4) | 0 | 3 (11) | 4 (5) |
| Dizziness | 0 | 1 (4) | 3 (10) | 1 (4) | 5 (6) |
| Diarrhea | 2 (5) | 3 (11) | 0 | 1 (4) | 4 (5) |
N= number of patients; n =number of patients experiencing the event; q2wks = every 2 weeks; q4wks = every 4 weeks
aInjection site reactions include: pain, erythema, bruising, hematoma, hemorrhage, pruritus, swelling, induration, paraesthesia, reaction, warmth, edema and rash.
bIncludes upper respiratory infection, viral upper respiratory infection
cIncludes headache, tension headache, sinus headache
dIncludes rash, rash maculopapular, rash erythematous
TAKHZYRO Prescribing Information
Were there any differences in side effects among sex, race and age?
- Sex: The occurrence of side effects was similar in males and females.
- Race: The majority of patients was White. The number of patients of other races was limited; therefore, differences in the occurrence of side effects among races could not be determined.
- Age: The majority of patients was less than 65 years of age. The number of patients 65 years and older was limited; therefore, differences in the occurrence of 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?
The table below summarizes the occurrence of the most common adverse reaction, injection site reactions, by subgroup.
Table 5. Pooled Subgroup Analysis of Injection Site Reactions (Trial 1)
| Demographic Characteristic | Placebo n/N (%) | TAKHZYRO n/N (%) |
|---|---|---|
| Sex | ||
| Male | 2/7 (29) | 11/30 (37) |
| Female | 12/34 (35) | 33/54 (61) |
| Race | ||
| White | 14/39 (36) | 36/74 (49) |
| Black or African American | 0/2 (0) | 7/8 (88) |
| Asian | 0/0(0) | 1/2 (50) |
| Age Group | ||
| 65=""> | 14/39 (36) | 43/82 (52) |
| > 65 years | 0/2 (0) | 1/3 (33) |
Clinical Trial Data
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the clinical trials?
The FDA approved TAKHZYRO based on evidence from one clinical trial (Trial 1 /NCT02586805) of 125 patients with hereditary angioedema. The trial was conducted at 41 sites in Canada, Europe, Jordan, and the United States.
Figure 1 summarizes how many males and females were in the clinical trial used to evaluate safety and efficacy.
Figure 1. Baseline Demographics by Sex
FDA Review
Figure 2 summarizes the percentage of patients by race in the clinical trial used to evaluate safety and efficacy.
Figure 2. Baseline Demographics by Race
FDA Review
Table 1. Demographics of Trial 1 by Race
| Race | Number of Patients | Percentage of Patients |
|---|---|---|
| White | 113 | 90% |
| Black or African American | 10 | 8% |
| Asian | 2 | 2% |
FDA Review
Figure 3. Baseline Demographics by Age
FDA Review
Who participated in the trials?
The table below summarizes demographics of all patients in the clinical trial.
Table 6. Baseline Characteristics of Trial 1
| Demographic Parameters | Placebo (N=41) n (%) | TAKHZYRO Treatment Groups (N=84) | Total (N= 125) n (%) | ||
|---|---|---|---|---|---|
| 150 mg Q 4 weeks (N=28) n (%) | 300mg Q 4 weeks (N=29) n (%) | 300 Q 2 weeks (N=27) n (%) | |||
| Sex | |||||
| Male | 7 (17) | 8 (29) | 10 (35) | 12 (44) | 37 (30) |
| Female | 34 (83) | 20 (71) | 19 (66) | 15 (56) | 88 (70) |
| Race | |||||
| White | 39 (95) | 25 (89) | 23 (79) | 26 (96) | 113 (94) |
| Black or African American | 2 (5) | 1 (4) | 6 (21) | 1 (4) | 10 (8) |
| Asian | 0 | 2 (7) | 0 | 0 | 2 (2) |
| Age | |||||
| Mean years (SD) | 40 (17) | 43 (15) | 39 (13) | 40 (13) | 40 (15) |
| Median (years) | 42 | 45 | 40 | 38 | 42 |
| Min, max (years) | 12, 70 | 15, 73 | 12, 59 | 15, 61 | 12, 73 |
| Age Group | |||||
| 18=""> | 4 (10) | 1 (4) | 3 (10) | 2 (7) | 10 (8) |
| ≥ 18 to 65> | 35 (85) | 24 (86) | 26 (90) | 25 (93) | 110 (88) |
| ≥ 65 years | 2 (5) | 3 (11) | 0 | 0 | 5 (4) |
| Ethnicity | |||||
| Hispanic | 3 (7) | 1 (4) | 2 (7) | 3 (11) | 9 (7) |
| Not Hispanic | 38 (93) | 27 (96) | 38 (93) | 23 (85) | 115 (92) |
| Unknown | 0 | 0 | 0 | 1 (4) | 1 (1) |
| Region | |||||
| United States | 25 (61) | 20 (71) | 23 (79) | 18 (67) | 86 (69) |
| Canada | 3 (7) | 1 (4) | 1 (3) | 2 (7) | 7 (6) |
| Europe | 12 (29) | 6 (21) | 4 (14) | 7 (26) | 29 (23) |
| Jordan | 1 (2) | 1 (4) | 1 (3) | 0 | 3 (2) |
FDA Review
How were the trials designed?
The benefit and side effects of TAKHZYRO were evaluated in one clinical trial. Trial investigators observed patients 12 years and older with hereditary angioedema (HAE) to determine the number of attacks for each patient. The trial enrolled patients with at least 1 attack during the 4-week period. Patients were assigned to receive one of three doses of TAKHZYRO once every 2 or 4 weeks, or placebo once every 2 weeks for 26 weeks. Neither the patients nor the investigators knew which treatment was being given until after the trial was completed. All patients could use other medications for treatment of acute attacks.
Trial investigators recorded the number of angioedema attacks in all treated groups over the 26 weeks. The benefit of TAKHZYRO was assessed by comparing the reduction rate of HAE attacks to placebo over a 26-week treatment period.
How were the trials designed?
The efficacy and safety of TAKHZYRO were established in one randomized, double-blind, placebo-controlled trial. The trial evaluated TAKHZYRO for the prevention of angioedema attacks in adult and adolescent patients with Type I or II hereditary angioedema who experienced at least one investigator-confirmed attack per 4 weeks, during the run-in period. Patients were randomized into one of four parallel treatment arms, stratified by baseline attack rate (placebo, TAKHZYYRO 150 mg every 4 weeks, TAKHZYYRO 300 mg every 4 weeks, or TAKHZYYRO 300 mg every 2 weeks by subcutaneous injection) for 26 weeks. All patients could use rescue medications for treatment of breakthrough angioedema attacks.
The primary efficacy endpoint was the reductions in the mean HAE attack rate compared to placebo during the 26-week treatment period.
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