Drugs

Drug Trials Snapshots: ORKAMBI

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 ORKAMBI Prescribing Information for complete information.

ORKAMBI (lumacaftor/ivacaftor)
(or KAM bee)
Vertex Pharmaceuticals, Inc.
Approval date: July 2, 2015


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

ORKAMBI is a treatment for cystic fibrosis (CF) in patients 12 years and older with two copies of a specific gene mutation called F508del. Having two copies of this mutation (one inherited from each parent) is the leading cause of CF.

CF is a serious genetic disorder that results in the formation of thick mucus that builds up in the lungs and other parts of the body. This can lead to severe breathing problems.

How is this drug used?

ORKAMBI is a tablet that is taken every 12 hours.

What are the benefits of this drug?

ORKAMBI improved lung function by allowing air to move easier.

What are the benefits of this drug (results of trials used to assess efficacy)?

The figures below summarize the primary endpoint results for the trials percent predicted FEV1 (ppFEV1). The population represents all randomized patients who were treated.

Figure 4. Summary of Efficacy in Trial 1

Figure summarizing the primary endpoint results for the trials. The population represents all randomized patients who were treated.

LS = least squares

 ORKAMBI least squaresORKAMBI

 Placebo least squares Placebo

Source: ORKAMBI Prescribing Information, Section 14, Figure 1

Figure 5. Summary of Efficacy in Trial 2

Figure summarizing the primary endpoint results for the trials. The population represents all randomized patients who were treated.

 

LS = least squares

 ORKAMBI least squaresORKAMBI

 Placebo least squares Placebo

Source: ORKAMBI Prescribing Information, Section 14, Figure 1

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:  ORKAMBI worked similarly in males and females.
  • Race:  Most of the patients in the trials were White. Differences in response to ORKAMBI among races could not be determined.
  • Age:  ORKAMBI worked similarly in all age groups studied.

Were there any differences in how well the drug worked in clinical trials among sex, race1, and age groups?

The tables below summarize the primary endpoint results by subgroup.

Table 2. Subgroup Analysis of Primary Endpoint*, Trial 1


Subgroup
ORKAMBIPlaceboDifference vs. placebo95 % CI
LS Mean (SE)Total, nLS Mean
(SE)
Total, nLLUL
All patients2.16 (0.530)172-0.44 (0.524)1802.601.184.01
Sex
Male2.09 (0.725)94-0.53 (0.730)962.620.654.59
Female2.34 (0.784)78-0.30 (0.758)842.640.574.71
Age Group
>=12 to <18 years3.67 (1.208)49-0.45 (1.217)494.120.757.50
>=18 years1.41 (0.555)123-0.61 (0.541)1312.020.553.50

1Race not included due to small number of non-white patients
*Primary Endpoint=absolute change in percent predicted forced expiratory volume (ppFEV1) from baseline
LL=lower limit, UL=upper limit
Source: Company Clinical Trial Data

Table 3. Subgroup Analysis of Primary Endpoint*, Trial 2


Subgroup
ORKAMBIPlaceboDifference vs. placebo95 % CI
LS Mean
(SE)
Total, nLS Mean
(SE)
Total, nLLUL
All patients2.85 (0.540)180-0.15 (0.539)1833.001.564.44
Sex
Male3.24 (0.844)84-0.50 (0.839)873.751.525.98
Female2.45 (0.703)960.14 (0.705)962.320.434.20
Age Group
>=12 to <18 years2.43 (1.282)440.77 (1.326)421.66-1.955.27
>=18 years2.75 (0.570)136-0.71 (0.560)1413.461.924.99

1Race not included due to small number of non-white patients
*Primary Endpoint=absolute change in percent predicted forced expiratory volume (ppFEV1) from baseline
LL=lower limit, UL=upper limit
Source: Company Clinical Trial Data

What are the possible side effects?

The most commonly reported side effects associated with ORKAMBI are shortness of breath, common cold, nausea, diarrhea, vomiting, and gas.

What are the possible side effects (results of trials used to assess safety)?

The table below summarizes side effects in the clinical trials. The population represented is any patient who received at least one dose of study drug.

Table 4. Adverse Drug Reactions in ≥5% of ORKAMBI‑Treated Patients

Adverse ReactionORKAMBI
N=369
n (%)
Placebo
N=370
n (%)
Dyspnea48 (13)29 (8)
Nasopharyngitis48 (13)40 (11)
Nausea46 (13)28 (8)
Diarrhea45 (12)31 (8)
Upper respiratory tract infection37 (10)20 (5)
Fatigue34 (9)29 (8)
Respiration abnormal32 (9)22 (6)
Blood creatine phosphokinase increased27 (7)20 (5)
Rash25 (7)7 (2)
Flatulence24 (7)11 (3)
Rhinorrhea21 (6)15 (4)
Influenza19 (5)8 (2)

Source: ORKAMBI Prescribing Information, Section 6, Table 1

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 side effects appeared to be similar in males and females.
  • Race:  Most of the patients in the trials were White. The risk of side effects among races could not be determined.
  • Age: The risk of side effects was similar in all age groups studied.

Were there any differences in side effects of the clinical trials among sex, race1, and age groups?

The table below summarizes side effects by subgroups that occurred during the trial.

Table 5. Subgroup Analysis of Side Effects


Subgroup
ORKAMBIPlacebo
x (%)Total, nx (%)Total, n
Any TEAEs351 (95)369355 (96)370
Sex
Male175 (94)187176 (93)189
Female176 (97)182179 (99)181
Age Group
>=12 to <18 years94 (96)9893 (97)96
>=18 years257 (95)271262 (96)274

1 Race not included due to small number of non-white patients
Source: Company Clinical Trial Data

WHO WAS IN THE CLINICAL TRIALS

Who participated in the clinical trials?

The FDA approved ORKAMBI based on evidence from two clinical trials that enrolled 1108 patients with cystic fibrosis. All patients had to have two copies of a specific mutation (known as the F508del mutation) in the CFTR gene in order to participate. The trials were conducted in the United States, Canada, Europe, and Australia. The same trials were used to assess benefits and side effects of the drug.

The figure below summarizes how many men and women were enrolled in the clinical trials.

Figure 1. Baseline Demographics by Sex

Pie chart summarizing how many men and women were enrolled in the clinical trials used to evaluate efficacy of the drug ORKAMBI. In total, 563 men (51%) and 545 women (49%) participated in the clinical trials used to evaluate efficacy of the drug ORKAMBI

Source: Company Clinical Trial Data

The figure and the table below summarizes the percentage of patients by race enrolled in the clinical trials. CF is uncommon among non-whites.

Figure 2. Baseline Demographics by Race

Bar chart summarizing the percentage of patients by race enrolled in the ORKAMBI clinical trial. In total, 1093 White (99%) and 15 identified as Other (1%).

*=includes African American, Asian, American Indian or Alaska Native, and unknown
Source: Company Clinical Trial Data

Table 1. Baseline Demographics by Race

RaceNumber of PatientsPercentage of Patients
  White109399%
  Other*151%

*=includes African American, Asian, American Indian or Alaska Native, and unknown
Source: Company Clinical Trial Data

The figure below summarizes how many patients by age were enrolled in the clinical trial.

Figure 3. Baseline Demographics by Age

Pie chart summarizing how many individuals of certain age groups were enrolled in the ORKAMBI clinical trial. In total, 290 were 12 to 17 years (26%) and 818 were 18 years and older (74%).

Source: Company Clinical Trial Data

Who participated in the trials?

The table below summarizes baseline demographics for the enrolled population for the two trials.

Table 6. Baseline Demographics for the Trials

 ORKAMBI
(N=369)
n (%)
 Lumacaftor/ivacaftor *
 (N=368)
 n (%)
Placebo
(N=371)
n (%)
Total
(N=1108)
n (%)
Sex
  Male187 (51)186 (51)190 (51)563 (51)
  Female182 (50)182 (49)181 (49)545 (49)
Age
  Mean years (SD)25 (10)25 (9)25 (10)25 (10)
  Median (years)24232323
  Min, Max (years)12,5712. 5412,6412, 64
Age Group
  >=12 to <18 years98 (27)96 (26)96 (26)290 (26)
  >=18 years271 (73)272 (74)275 (74)818 (74)
Race
  White361 (98)363 (99)369 (100)1093 (99)
  Black or African
American
1(<1)1(<1)1(<1)3 (<1)
  Asian01(<1)01(<1)
  American Indian or
Alaska   Native
1(<1)001(<1)
  Unknown2 (1)1(<1)1(<1)4 (<1)
 Other4 (1)2(1)06 (1)
Ethnicity
Hispanic or Latino9 (2)12 (3)13 (4)34 (3)
Non Hispanic or Latino358 (97)352 (96)356 (96)1066 (96)
Unknown2 (1)4 (1)2 (1)8 (1)
Region
  North America202 (55)215 (58)221 (60)638 (58)
  Europe134 (36)124 (34)121 (32)379 (34)
  Australia33 (9)29 (8)29 (8)91 (8)

*not an approved strength (lumacaftor 600 mg/ivacaftor 250mg)
Source: Company Clinical Trial Data

How were the trials designed?

There were two trials that evaluated the benefits and side effects of ORKAMBI. In the trials, patients were randomly assigned to receive either ORKAMBI, a different dose of the two drugs in ORKAMBI (lumacaftor/ivacaftor), or placebo. Neither the patients nor the health care providers knew which treatment was being given until after the trials were completed.

The trial measured the improvement in lung function after 24 weeks of treatment and compared ORKAMBI to placebo.

How were the trials designed?

The efficacy of ORKAMBI in patients with cystic fibrosis (CF) who are homozygous for the F508del mutation in the CFTR gene was evaluated in two randomized, double‑blind, placebo‑controlled, 24‑week clinical trials (Trials 1 and 2) in 1108 clinically stable patients with CF.

The primary efficacy endpoint in both studies was change in lung function as determined by absolute change from baseline in ppFEV1 at Week 24.

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

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Page Last Updated: 07/30/2015
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