Drug Trials Snapshots: DAKLINZA
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 DAKLINZA Prescribing Informationfor complete information.
DAKLINZA (daclatasvir)
(dak lin za)
Bristol-Myers-Squibb
Approval date: July 24, 2015
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
DAKLINZA is a drug for the treatment of a specific type of Hepatitis C, called chronic Hepatitis C genotype 3 infection. It is to be used in combination with another drug called sofosbuvir.
Hepatitis C is a virus that causes inflammation of the liver that can lead to decreased liver function or liver failure. Approximately 10% of Hepatitis C infections in the United States result from genotype 3 infection.
How is this drug used?
DAKLINZA is a tablet that is taken once a day together with sofosbuvir.
What are the benefits of this drug?
DAKLINZA in combination with sofosbuvir may show that the hepatitis C virus is no longer detected in the blood at least 12 weeks after finishing treatment (called a sustained virologic response), suggesting HCV infection has been cured.
What are the benefits of this drug?
The table below summarizes the percentage of subjects who achieved the primary efficacy endpoint for treatment-naïve and treatment-experienced (previously-treated) patients. The primary endpoint was Sustained Virologic Response (SVR) at post-treatment week 12 and was defined as HCV RNA below the lower limit of quantification of 25 IU per mL.
Table 2. Summary of Efficacy Results
| Treatment Outcomes | Treatment- Naive N=101 |
Treatment- Experienced N=51 |
Total N=152 |
|---|---|---|---|
|
SVR* All |
90% (91/101) |
86% (44/51) |
89% (135/152) |
|
Outcomes for subjects without SVR |
1% (1/101) |
0 |
0.7% (1/152) |
*SVR =Sustained Virologic Response
a Includes 11 subjects with missing or inconclusive cirrhosis status.
b One subject had quantifiable HCV RNA at end of treatment.
c Relapse rates are calculated with a denominator of subjects with HCV RNA not detected at the end of treatment.
Source: DAKLINZA Prescribing Information Section 14, Table 8
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
Subgroup analyses were conducted for sex, race, and age.
- Sex: DAKLINZA worked similarly in men and women.
- Race: Most of the patients in the trial were white. Differences in response to DAKLINZA among races could not be determined.
- Age: Most of the patients in the trial were less than 65 years of age. DAKLINZA worked similarly in patients younger than 65 years and patients 65 years and older.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
The table below summarizes the primary endpoint by subgroup.
Table 3. Subgroup Analysis of Primary Endpoint
| Subgroup | Total (N=152) n/N, (%) |
|---|---|
| Overall Response/All patients | 135/152 ( 89) |
| Sex | |
| Male | 77/90 ( 86) |
| Female | 58/62 ( 94) |
| Age Group | |
| 17 - 64 years | 128/142 ( 90) |
| >=65 years | 7/10 ( 70) |
| Race | |
| White | 120/137 ( 88) |
| Black or African American | 6/6 (100) |
| Asian | 7/7 (100) |
| American Indian or Alaska Native | 2/2 (100) |
Source: Company Trial Data
What are the possible side effects?
The most common side effects are headache and tiredness.
What are the possible side effects?
The table below summarizes adverse reactions from the trial.
Table 4. Adverse Reactions Reported at ≥5% Frequency
| Adverse reaction | DAKLINZA (N= 152 ) n (%) |
|---|---|
| Headache | 21 (14%) |
| Fatigue | 21 (14%) |
| Nausea | 12 (8%) |
| Diarrhea | 7 (5%) |
Source: DAKLINZA Prescribing Information Section 6, Table 2
Were there any differences in side effects among sex, race and age?
Subgroup analyses were conducted for sex, race, and age.
- Sex: The risk of overall side effects appeared to be similar in men and women.
- Race: Most of the patients in the trial were white. Differences in side effects among races could not be determined.
- Age: Most of the patients in the trial were younger than 65 years. The risk of overall side effects appeared to be similar in patients younger than 65 years and patients 65 years and older.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
The tables below summarize adverse events, including headache and fatigue, by subgroup.
Table 5. Subgroup Analysis of Any Adverse Event
| Subgroup | Total (N=152) n/N, (%) |
|---|---|
|
Any On-treatment AEs |
107/152 ( 70) |
| Sex | |
|
Male |
62/90 ( 69) |
|
Female |
45/62 ( 73) |
| Age Group | |
|
17 - 64 years |
100/142 ( 70) |
|
>=65 years |
7/10 ( 70) |
| Race | |
|
White |
98/137 ( 72) |
|
Black or African American |
3/6 ( 50) |
|
Asian |
4/7 ( 57) |
|
American Indian or Alaska Native |
2/2 (100) |
Source: Company Trial Data
Table 6. Subgroup Analysis of Adverse Event-Headache
| Subgroup | Total (N=152) n/N, (%) |
|---|---|
|
Any On-treatment Headache |
30/152 ( 20) |
| Sex | |
|
Male |
17/90 ( 19) |
|
Female |
13/62 ( 21) |
| Age Group | |
|
17 - 64 years |
29/142 ( 20) |
|
>=65 years |
1/10 ( 10) |
| Race | |
|
White |
25/137 ( 18) |
|
Black or African American |
2/6 ( 33) |
|
Asian |
1/7 ( 14) |
|
American Indian or Alaska Native |
2/2 (100) |
Source: Company Trial Data
Table 7. Subgroup Analysis of Adverse Event-Fatigue
| Subgroup | Total (N=152) n/N, (%) |
|---|---|
| Any On-treatment Fatigue | 107/152 ( 70) |
| Sex | |
| Male | 62/90 ( 69) |
| Female | 45/62 ( 73) |
| Age Group | |
| 17 - 64 years | 100/142 ( 70) |
| >=65 years | 7/10 ( 70) |
| Race | |
| White | 98/137 ( 72) |
| Black or African American | 3/6 ( 50) |
| Asian | 4/7 ( 57) |
| American Indian or Alaska Native | 2/2 (100) |
Source: Company Trial Data
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the clinical trials?
The FDA approved DAKLINZA primarily based on evidence from a clinical trial of 152 patients with hepatitis C genotype 3 infection. In this trial, some patients were previously treated for hepatitis C and some were never treated before. Some patients had cirrhosis and some did not. The trial was conducted in the United States and Puerto Rico.
This Snapshot focuses on the demographics of this trial. Additional data from other clinical trials were considered by FDA to approve DAKLINZA that are not included in this Snapshot.
The figure below summarizes how many men and women were enrolled in the clinical trial.
Figure 1. Baseline Demographics by Sex
Source: Company Trial Data
The figure and table below summarize the percentage of patients by race enrolled in the clinical trial.
Figure 2. Baseline Demographics by Race
Source: Company Trial Data
Table 1. Demographics of Efficacy Trials by Race
| Race | Number of Patients | Percentage of Patients |
|---|---|---|
| White | 137 | 90% |
| Black or African American | 6 | 4% |
| Asian | 7 | 5% |
| American Indian or Alaska Native | 2 | 1% |
Source: Company Trial Data
The figure below summarizes how many patients by age participated in the clinical trial.
Figure 3. Baseline Demographics by Age
Source: Company Trial Data
Who participated in the trial?
The table below summarizes baseline demographics.
Table 8. Baseline Demographics for the Trial
| Demographic Parameters | Total (N=152) n (%) |
|---|---|
| Sex | |
| Male | 90 (59) |
| Female | 62 (41) |
| Age | |
| Mean years (SD) | 52.3 (9.94) |
| Median (years) | 55 |
| Min, Max (years) | 24, 73 |
| Age Group | |
| 17 - 64 years | 142 ( 93) |
| >=65 years | 10 (7) |
| Race | |
| White | 137 ( 90) |
| Black or African American | 6 (4) |
| Asian | 7 (5) |
| American Indian or Alaska Native | 2 (1) |
| Ethnicity | |
| Hispanic or Latino | 25 (16) |
| Not Hispanic or Latino | 127 (84) |
| Region | |
| United States | 146 ( 96) |
| Puerto Rico | 6 (3) |
Source: Company Trial Data
How were the trials designed?
In the genotype 3 trial, all patients received DAKLINZA in combination with sofosbuvir once daily for 12 weeks and were followed up for 24 weeks post treatment. The trial measured the blood level of hepatitis virus C before and after treatment.
How were the trials designed?
The efficacy and safety of DAKLINZA in combination with sofosbuvir were evaluated in an open-label trial that included 152 subjects with chronic HCV genotype 3 infection and compensated liver disease. Both treatment-naïve and previously-treated patients were included.
Patients received DAKLINZA plus sofosbuvir once daily for 12 weeks and were monitored for 24 weeks post treatment.
The primary endpoint was Sustained Virologic Response (SVR) at post-treatment week 12 and was defined as HCV RNA below the lower limit of quantification of 25 IU per mL.
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