Drug Trials Snapshot: ALYFTREK
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 ALYFTREK Prescribing Information for all 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).
ALYFTREK (vanzacaftor/tezacaftor/deutivacaftor)
Ah-LIF-trek
Vertex Pharmaceuticals
Original Approval date: December 20, 2024
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
ALYFTREK is a medication for the treatment of cystic fibrosis (CF) in patients 6 years of age and older who have at least one F508del mutation or another responsive mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
How is this drug used?
ALYFTREK is an oral medication that is taken daily.
Who participated in the clinical trials?
The FDA approved ALYFTREK based on evidence from two clinical trials of 971 patients with CF. The trials were conducted at 212 of sites in 23 of countries in North America, Europe, and the rest of the world. Among the 971 patients enrolled in the trials, 39% were from the United States.
How were the trials designed?
ALYFTREK was evaluated in two clinical trials of 971 patients with CF. Both trials were designed as noninferiority trials in which ALYFTREK was compared to a combination drug containing elexacaftor, tezacaftor, and ivacaftor (ELX/TEZ/IVA), a common medication used to treat CF. All patients were treated with ELX/TEZ/IVA for 4 weeks then randomized to receive either ALYFTREK or ELX/TEZ/IVA for 52 weeks. The primary endpoint of both trials evaluated pulmonary function that was measured by the absolute change from baseline in the forced expiratory volume (FEV1) through 24 weeks.
How were the trials designed?
The efficacy and safety of ALYFTREK were evaluated in two phase 3, randomized, double-blind, parallel group, noninferiority trials in patients with CF 12 years of age and older, in which ALYFTREK was compared to ELX/TEZ/IVA. The trials included
a 4-week ELX/TEZ/IVA run-in period. Patients were then randomized in a 1:1 ratio to receive ALYFTREK (vanzacaftor 20 mg daily/tezacaftor 100 mg daily/deutivacaftor 250 mg daily) or ELX/TEZ/IVA (elexacaftor 200 mg daily/tezacaftor 100 mg daily/ivacaftor 150 mg every 12 hours) for a 52-week treatment period. The primary endpoint of both trials was the absolute change from baseline in the FEV1 through 24 weeks. Other endpoints assessed included the rate of CF pulmonary exacerbations and the change from baseline in sweat chloride, a pharmacodynamic measurement used in CF.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female patients were enrolled in the combined clinical trials used to evaluate the efficacy of ALYFTREK.
Figure 1. Baseline Demographics by Sex, Efficacy Population
Source: Adapted from FDA Review
Figure 2 summarizes how many patients by race were enrolled in the combined clinical trials used to evaluate the efficacy of ALYFTREK.
Figure 2. Baseline Demographics by Race, Efficacy Population
Source: Adapted from FDA Review
Figure 3 summarizes how many patients by age were enrolled in the combined clinical trials used to evaluate the efficacy of ALYFTREK.
Figure 3. Baseline Demographics by Age, Efficacy Population
Source: Adapted from FDA Review
Figure 4 summarizes how many patients by ethnicity were enrolled in the combined clinical trials used to evaluate the efficacy of ALYFTREK.
Figure 4. Baseline Demographics by Ethnicity, Efficacy Population
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Baseline Demographics of Efficacy Trials
| Characteristic | ALYFTREK | ELX/TEZ/IVA |
|---|---|---|
| N=480 | N=491 | |
| Sex | ||
| Female | 215 (44.8) | 228 (46.4) |
| Male | 265 (55.2) | 263 (53.6) |
| Age group, years | ||
| <18 | 67 (14.0) | 69 (14.1) |
| 18 to 65 | 411 (85.6) | 420 (85.5) |
| ≥65 | 2 (0.4) | 2 (0.4) |
| Race | ||
| Asian | 2 (0.4) | 1 (0.2) |
| Black or African American | 4 (0.8) | 1 (0.2) |
| Not reported | 10 (2.1) | 23 (4.7) |
| Other | 3 (0.6) | 7 (1.4) |
| White | 461 (96.0) | 459 (93.5) |
| Ethnicity | ||
| Hispanic or Latino | 17 (3.5) | 16 (3.3) |
| Not Hispanic or Latino | 448 (93.3) | 451 (91.9) |
| Not reported | 15 (3.1) | 24 (4.9) |
| Geographic region | ||
| North America | 201 (41.9) | 194 (39.5) |
| Rest of world | 279 (58.1) | 297 (60.5) |
Source: Adapted from FDA Review
What are the benefits of this drug?
In patients with CF over the age of 12 years with a response CFTR mutation, ALYFTREK was demonstrated to be noninferior to, or not worse than, ELX/TEZ/IVA. This was measured by the primary endpoint of the absolute change from baseline in percent predicted FEV1 through 24 weeks of treatment.
What are the benefits of this drug (results of trials used to assess efficacy)?
The two phase 3 trials demonstrated that treatment with ALYFTREK was noninferior to ELX/TEZ/IVA in CF patients ages 12 years and older with a responsive CFTR mutation. This was measured by the primary endpoint of the absolute change from baseline in percent predicted FEV1 through 24 weeks. The efficacy was also supported by other endpoints including the rate of CF pulmonary exacerbations, results of the CF Questionnaire, Revised, respiratory domain, and the change from baseline in sweat chloride (a pharmacodynamic measurement used in CF).
Table 2. Absolute Change From Baseline in Percent Predicted FEV1 Through 24 Weeks, Efficacy Population
| Parameter | Trial 1 |
Trial 2 |
||
|---|---|---|---|---|
| ALYFTREK | ELX/TEZ/IVA | ALYFTREK | ELX/TEZ/IVA | |
| N=196 | N=202 | N=284 | N=289 | |
| n | 187 | 193 | 268 | 276 |
| LS mean (SE) | 0.5 (0.3) | 0.3 (0.3) | 0.2 (0.3) | 0.0 (0.2) |
| LS mean difference (95% CI) | 0.2 (-0.7, 1.1) | 0.2 (-0.5, 0.9) | ||
Source: Adapted from FDA Review
Abbreviations: CI, confidence interval; ELX, elexacaftor; FEV1, forced expiratory volume in 1 second; IVA, ivacaftor; LS, least squares; SE, standard error; TEZ, tezacaftor
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: The effect of ALYFTREK was similar for females and males.
- Race: The number of patients of races other than White was small; therefore, differences in how ALYFTREK worked among races could not be determined.
- Age: The number of patients older than 65 years of age was small; therefore, differences in how ALFTREK worked in patients younger and older than 65 years of age could not be determined.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Subgroup analyses of the primary endpoint based on age and gender at birth were performed. In general, there were no significant differences in the efficacy of ALYFTREK based on the demographic subgroups. The subgroup efficacy analysis data are included in Table 3.
Table 3. Efficacy Results by Subgroup, Efficacy Population
| Subgroup | Trial 1 |
Trial 2 |
||
|---|---|---|---|---|
| n[A], n[E] | LS Mean Difference (95% CI) | n[A], n[E] | LS Mean Difference (95% CI) | |
| Age at screening, years | ||||
| <18 | 23, 28 | -1.3 (-3.9, 1.3) | 38, 33 | 0.9 (-1.2, 3) |
| ≥18 | 164, 165 | 0.4 (-0.5, 1.4) | 230, 243 | 0 (-0.7, 0.8) |
| Sex | ||||
| Male | 114, 114 | -0.1 (-1.3, 1.1) | 138, 134 | 0.3 (-0.6, 1.3) |
| Female | 73, 79 | 0.5 (-0.9, 1.8) | 130, 142 | 0.1 (-0.9, 1.2) |
Source: Adapted from FDA Review
Abbreviations: CI, confidence interval; ELX, elexacaftor; IVA, ivacaftor; LS, least squares; n[A], number of subjects included in the analysis in the ALYFTREK arm; n[E], number of subjects included in the analysis in the ELX/TEZ/IVA arm; TEZ, tezacaftor
What are the possible side effects?
The most common side effects of ALYFTREK included cough, pain or swelling of the nose or throat (nasopharyngitis), upper respiratory tract infection (common cold) including stuffy and runny nose, headache, mouth or throat pain, flu (influenza), tiredness, increase liver enzymes, rash, and sinus congestion.
Elevated liver enzymes have been observed in patients taking ALYFTREK. Cases of serious liver damage and liver failure leading to transplantation and death have been seen in some people with or without a history of liver problems taking ELX/TEZ/IVA, which has the same or similar active ingredients as ALYFTREK. Close monitoring of blood tests to check your liver is recommended when starting ALYFTREK.
What are the possible side effects (results of trials used to assess safety)?
The safety profile of ALYFTREK was based on the combined safety population from the two noninferiority phase 3 trials. The overall safety profile of ALYFTREK was similar to ELX/TEZ/IVA. ALYFTREK contains ingredients that are the same or similar to the ingredients in another combination drug containing ELX/TEZ/IVA, which can cause serious liver damage and liver failure in patients with and without a history of liver disease. Increases in liver function tests have been observed with ALYFTREK treatment. Close monitoring of liver function tests is recommended when starting ALYFTREK.
The most common side effects, those that occurred in greater than 5% of treated subjects and greater than 1% more frequently with ALYFTREK than ELX/TEZ/IVA, are reviewed in Table 4.
Table 4. Safety Results, Safety Population
| Adverse Reactions | ALYFTREK | ELX/TEZ/IVA |
|---|---|---|
| N=480 | N=491 | |
| n (%) | n (%) | |
| Cougha | 120 (25) | 116 (24) |
| Nasopharyngitis | 102 (21) | 95 (19) |
| Upper respiratory tract infectionb | 101 (21) | 97 (12) |
| Headache | 76 (16) | 69 (13) |
| Oropharyngeal pain | 69 (14) | 60 (12) |
| Influenza | 52 (11) | 26 (5) |
| Fatigue | 51 (11) | 46 (9) |
| ALT increased | 38 (8) | 29 (6) |
| Rash | 37 (8) | 22 (4) |
| AST increased | 33 (7) | 27 (6) |
| Sinus congestion | 32 (7) | 15 (3) |
Source: Adapted from ALYFTREK Prescribing Information
a Cough is composed of several similar terms including productive cough
b Upper respiratory tract infection is composed of several similar terms including viral upper respiratory tract infection
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ELX, elexacaftor; IVA, ivacaftor; TEZ, tezacaftor
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 number of patients of races other than White was small. Therefore, Differences in the occurrence of side effects among races could not be determined
- Age: The occurrence of side effects was similar in patients younger and older than18 years of age. Differences in the occurrence of side effects in patients younger and older than 65 years of age could not be determined because of the small number of enrolled patients over 65 years of age.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
A safety analysis by key demographic subgroups including age, gender at birth, and region (United States versus outside the United States) was performed. There were no significant differences noted between subgroups. The side effects by demographic subgroups are reviewed in Table 5.
Table 5. Side Effects by Subgroup, Safety Population
| Subgroup | ALYFTREK | ELX/TEZ/IVA | |
|---|---|---|---|
| N=480 | N=491 | ||
| n/Ns (%) | n/Ns (%) | ||
| Sex | |||
| Female | 201/215 (93.5) | 215/228 (94.3) | |
| Male | 258/265 (97.4) | 254/263 (96.6) | |
| Age group, years | |||
| <18 | 60/67 (89.6) | 63/69 (91.3) | |
| ≥18 | 399/413 (96.6) | 406/422 (96.2) | |
| Region | |||
| United States | 183/189 (96.8) | 173/177 (97.7) | |
| Non-United States | 276/291 (94.8) | 296/314 (94.3) | |
Source: Adapted from FDA Review
Abbreviations: ELX, elexacaftor; IVA, ivacaftor; N, number of patients in treatment arm; n, number of patients with adverse event; Ns, total number of patients for each specific subgroup and were assigned to that specific arm; TEZ, tezacaftor
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.
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