Drug Trials Snapshot: ATTRUBY
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 ATTRUBY 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).
ATTRUBY (acoramidis)
ah-troo-be
BridgeBio Pharma, Inc.
Original Approval date: November 22, 2024
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
ATTRUBY is a transthyretin stabilizer that is indicated for the treatment of the cardiomyopathy of wild-type or variant transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular (CV) death and CV-related hospitalization.
How is this drug used?
ATTRUBY is a tablet that is taken orally twice daily.
Who participated in the clinical trials?
The FDA approved ATTRUBY based on evidence of efficacy and safety from a clinical trial of 611 patients with wild-type or variant (hereditary or de novo) transthyretin cardiomyopathy (ATTR CM). The safety population comprised of 421 trial participants.
The trial was conducted at 95 sites in 18 countries including the United States, United Kingdom, Australia, Italy, Spain, Denmark, Canada, Czech Republic, New Zealand, Belgium, Israel, Netherlands, Greece, Brazil, Ireland, South Korea, Poland, and Portugal.
Of the 632 randomized patients in the trial, 126 (20%) patients (80 on ATTURBY, 46 on placebo) were from the United States.
How were the trials designed?
ATTRUBY was evaluated in a single phase 3 clinical trial of 611 patients with ATTR-CM.
Trial AG10-301 was a two-arm, double-blind, parallel design trial with 632 subjects randomized in a 2:1 ratio to ATTRUBY 712 mg twice daily (equivalent to 800 mg acoramidis HCl) or matching placebo (421 to ATTRUBY and 211 to placebo) and followed for 30 months at which time all randomized subjects were eligible to enroll in the open-label extension trial (AG10-304).
The trial featured an embedded design with Part A cohort consisting of a 12-month functional and health-related quality of life endpoints, and Part B cohort consisting of a 30-month mortality, morbidity, and functional endpoints. Part A did not meet its primary endpoint of change from baseline in 6-Minute Walk Distance (6MWD) at Month 12 (difference in least-squares [LS] mean: -2 meters, p=0.76) and Part B continued as specified in the protocol. The efficacy analyses are based on the results from AG10-301 Part B.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female patients were enrolled in the clinical trial used to evaluate the efficacy of ATTRUBY.
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 clinical trial used to evaluate the efficacy of ATTRUBY.
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 clinical trial used to evaluate the efficacy of ATTRUBY.
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 clinical trial used to evaluate the efficacy of ATTRUBY.
Figure 4. Baseline Demographics by Ethnicity, Efficacy Population
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Baseline Demographics, Trial AG10-301
Subgroup | ATTRUBY N=409 n (%) | Placebo N=202 n (%) | Overall N=611 n (%) |
---|---|---|---|
Sex | |||
Male | 374 (91.4) | 181 (89.6) | 555 (90.8) |
Female | 35 (8.6) | 21 (10.4) | 56 (9.2) |
Age group, years | |||
<78 | 198 (48.4) | 101 (50.0) | 299 (48.9) |
≥78 | 211 (51.6) | 101 (50.0) | 312 (51.1) |
Race | |||
White | 358 (87.5) | 179 (88.6) | 537 (87.9) |
Black or African American | 19 (4.7) | 10 (5.0) | 29 (4.8) |
Asian | 10 (2.4) | 3 (1.4) | 13 (2.1) |
Other* | 22 (5.4) | 10 (5.0) | 32 (5.2) |
Ethnicity | |||
Hispanic or Latino | 7 (1.7) | 4 (2.0) | 11 (1.8) |
Not Hispanic or Latino | 391 (95.6) | 191 (94.6) | 582 (95.3) |
Not reported or Unknown | 11 (2.7) | 7 (3.4) | 18 (2.9) |
Source: Adapted from FDA Review
* Includes: American Indian or Alaska Native (n=1), Multiple (n=2), Native Hawaiian (n=1), and not reported (n=22)
What are the benefits of this drug?
Trial AG10-301 demonstrated that ATTRUBY reduces the risk of CV death and CV-related hospitalization and improves functional capacity and symptoms in patients with ATTR-CM. ATTRUBY belongs to the same drug class as the already approved drug, tafamidis. Hence, ATTRUBY represents another treatment option for patients with ATTR-CM.
What are the benefits of this drug (results of trials used to assess efficacy)?
The primary efficacy endpoint for AG10-301 Part B was a hierarchical combination of all-cause mortality, cumulative frequency of CV-related hospitalization, change from baseline in NT-proBNP, and change from baseline in 6MWD over a 30-month fixed treatment duration.
AG10-301 Part B met its primary endpoint (hierarchical combination of all-cause mortality, cumulative frequency of CV-related hospitalization, change from baseline in NT-proBNP, and change from baseline in 6MWD over the 30-month trial duration) demonstrating a treatment effect of ATTRUBY relative to standard of care (win ratio [96% CI]: 1.77 [1.4, 2.2], p<0.0001). All components of the composite primary endpoint also demonstrated consistent positive trends in favor of ATTRUBY compared to placebo over the 30-month trial period.
Analysis of the first two components of the primary efficacy endpoint, all-cause mortality and frequency of CV-related hospitalizations, over the 30-month trial duration also demonstrated a treatment effect of ATTRUBY compared to placebo (p=0.018).
Treatment effect favoring ATTRUBY was also observed on the secondary endpoints of change from baseline in 6MWD (difference in LS mean [95% CI]: 40 [21, 58] m) and change from baseline in Kansas City Cardiomyopathy Questionnaire overall summary (KCCQ-OS; difference in LS mean [95% CI]:10 [6, 14] points) at Month 30.
Were there any differences in how well the drug worked in clinical trials among sex, race, age, and ethnicity?
- Sex: The effect of ATTURUBY was similar for males and females.
- Race: The number of patients of races other than White was small; therefore, differences in how ATTURUBY worked among races could not be determined.
- Age: The effect of ATTURUBY was similar in patients younger and older than 78 years of age.
- Ethnicity: The number of patients of ethnicities other than Not Hispanic or Latino was small; therefore, differences in how ATTURUBY worked according to ethnicity could not be determined.
Were there any differences in how well the drug worked in clinical trials among sex, race, age, and ethnicity groups?
The benefit of ATTURUBY was consistent across subgroups of sex and age.
Table 2 summarize how well ATTURUBY worked in the trial among sex, race, age, and ethnicity groups.
Table 2. Effect of ATTRUBY on Reducing the Risk of Primary Composite Outcomea by Subgroups, Trial AG10-301
Subgroup | Total Patients N=611 n (%) | Win Ratio (95% CI) |
---|---|---|
Sex | ||
Male | 555 (90.8) | 1.5 (1.1, 1.9) |
Female | 56 (9.2) | 1.7 (1.0, 3.4) |
Age | ||
<78 | 299 (48.9) | 1.8 (0.8, 2.8) |
≥78 | 312 (51.1) | 1.1 (0.5, 1.6) |
Race | ||
White | 537 (87.9) | 1.4 (1.0, 1.7) |
Black or African American | 29 (4.8) | 2.0 (1.0, 5.9) |
Asian | 13 (2.1) | - |
Other | 32 (5.2) | 1.7 (1.0, 5.1) |
Ethnicity | ||
Hispanic or Latino | 11 (1.8) | - |
Not Hispanic or Latino | 582 (95.3) | 1.5 (1.1, 1.9) |
Not reported or Unknown | 18 (2.9) | - |
Source: Adapted from FDA Review
a Primary composite outcome includes all-cause mortality and frequency of CV-related hospitalization
Abbreviations: CI, credible interval; CV, cardiovascular
What are the possible side effects?
The key safety risks with ATTRUBY are mild, gastrointestinal adverse reactions such as diarrhea and upper abdominal pain that generally do not require treatment discontinuation.
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 were White. The number of patients of other races was limited; therefore, differences in side effects among races could not be determined.
- Age: The occurrence of side effects was similar in patients younger and older than 65 years of age.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 3 shows subgroup analysis of gastrointestinal adverse reactions by subgroups based on safety population from the AG10-301.
Table 3. Subgroup Analysis of Gastrointestinal Adverse Reactions, Safety Population, AG10-301a
Demographic Characteristic | ATTRUBY N=421 n/Ns (%) | Placebo N=211 n/Ns (%) |
---|---|---|
Diarrhoea | ||
Total | 49/421 (11.6) | 16/211 (7.6) |
Sex | ||
Female | 4/37 (10.8) | 2/25 (8.0) |
Male | 45/384 (11.7) | 14/186 (7.5) |
Age group, years | ||
<65 | 2/12 (16.7) | 2/9 (22.2) |
≥65 | 47/409 (11.5) | 14/202 (6.9) |
Race | ||
White | 44/368 (12.0) | 15/187 (8.0) |
Black or African American | 2/20 (10.0) | 1/10 (10.0) |
Not reported | 3/16 (18.8) | 0/8 (0) |
Ethnicity | ||
Hispanic or Latino | 0/8 (0) | 0/4 (0) |
Not Hispanic or Latino | 47/401 (11.7) | 16/199 (8.0) |
Not reported or Unknown | 2/12 (16.7) | 0/8 (0) |
Upper abdominal pain | ||
Total | 23/421 (5.5) | 3/211 (1.4) |
Sex | ||
Female | 5/37 (13.5) | 0/25 (0) |
Male | 18/384 (4.7) | 3/186 (1.6) |
Age group, years | ||
<65 | 1/12 (8.3) | 0/9 (0) |
≥65 | 22/409 (5.4) | 3/202 (1.5) |
Race | ||
White | 20/368 (5.4) | 3/187 (1.6) |
Black or African American | 1/20 (5.0) | 0/10 (0) |
Not reported | 2/16 (12.5) | 0/8 (0) |
Ethnicity | ||
Hispanic or Latino | 1/8 (12.5) | 0/4 (0) |
Not Hispanic or Latino | 21/401 (5.2) | 3/199 (1.5) |
Not reported or Unknown | 1/12 (8.3) | 0/8 (0) |
Source: FDA Reviewer’s Analysis
a Duration is up to 30 months.
Abbreviations: N, number of subjects in treatment arm; n, number of subjects with adverse event; Ns, total number of subjects 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 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.