Overall KALYDECO® (ivacaftor) safety profile established in clinical trials

The overall safety profile for KALYDECO® (ivacaftor) is based on Trials 1, 2, and 31

  • The overall safety profile for KALYDECO is based on pooled data from 3 placebo-controlled clinical trials conducted in 353 patients age 6 years and older with CF who had a G551D mutation in the CFTR gene (Trials 1 and 2) or were homozygous for the F508del mutation (Trial 3)
  • KALYDECO is not indicated in patients with CF who are homozygous for the F508del mutation
     

Pooled safety data from Trials 1, 2, and 31,a,b

  • The proportion of patients who prematurely discontinued study drug due to adverse reactions (ARs) was 2% for patients treated with KALYDECO and 5% for patients treated with placebo
  • Serious ARs that occurred more frequently in patients treated with KALYDECO included:

ABDOMINAL PAIN

INCREASED HEPATIC ENZYMES

HYPOGLYCEMIA

  • The most common ARs in patients treated with KALYDECO in Trials 1, 2, and 3 (N=221) were headache (17%), upper respiratory tract infection (16%), nasal congestion (16%), nausea (10%), rash (10%), rhinitis (6%), dizziness (5%), arthralgia (5%), and bacteria in sputum (5%)1


Most common ARs in Trials 1 and 21
 

MOST COMMON ARs (≥ 8%) IN PATIENTS WITH A G551D MUTATION TREATED WITH KALYDECO AND GREATER THAN PLACEBO1

ADVERSE REACTION
(PREFERRED TERM)

KALYDECO
N=109,
n (%)

PLACEBO
N=104,
n (%) 

Headache 26 (24) 17 (16)
Oropharyngeal pain 24 (22) 19 (18)
Upper respiratory tract infection 24 (22) 14 (14)
Nasal congestion 22 (20) 16 (15)
Abdominal pain 17 (16) 13 (13)
Nasopharyngitis 16 (15) 12 (12)
Diarrhea 14 (13) 10 (10)
Rash 14 (13) 7 (7)
Nausea 13 (12) 11 (11)
Dizziness 10 (9) 1 (1)
  • The safety profile for the patients with CF enrolled in the other clinical trials (Trials 3-8) was similar to that observed in the 48-week placebo-controlled trials (Trials 1 and 2)1,c-g

Transaminase elevations in patients age 6 years and older1,a,b

  • In Trials 1, 2, and 3, the incidence of maximum transaminase (ALT or AST) >8, >5, or >3x ULN was 2%, 2%, and 6% in patients treated with KALYDECO and 2%, 2%, and 8% in patients treated with placebo, respectively
  • The proportion of patients who permanently discontinued treatment for elevated transaminases, all >8x ULN, was 0.5% for patients treated with KALYDECO and 2% for patients treated with placebo
    • 2 patients treated with KALYDECO were reported to have serious ARs of elevated liver transaminases compared to none on placebo
    • Transaminase elevations were more common in patients with a history of transaminase elevations

Transaminase elevations in patients age 4 months to less than 6 years1,e,g

  • In Trial 6, the incidence of patients experiencing transaminase elevations (ALT or AST) >3x ULN was 14.7% (5/34). All 5 patients had maximum ALT or AST levels >8x ULN, which returned to baseline levels following interruption of KALYDECO dosing
    • Transaminase elevations were more common in patients who had abnormal transaminases at baseline
    • KALYDECO was permanently discontinued in 1 patient
  • In Trial 8, the incidence of patients experiencing transaminase elevations (ALT or AST) >3, >5, and >8x ULN in the cohort of patients age 12 to <24 months was 27.8%, 11.1%, and 11.1%, respectively. In the cohort of patients age 6 to <12 months, 1 patient (9.1%) had elevated ALT of >3 to ≤5x ULN. In the cohort of patients age 4 to <6 months, no patients experienced transaminase elevations
    • No patients had elevations in total bilirubin or discontinued treatment due to transaminase elevations

aTrials 1 and 2 were 48-week, Phase 3, randomized, double-blind, placebo-controlled trials in 213 patients with a G551D mutation. Trial 1 patients were 12 years of age and older; Trial 2 patients were age 6 to 11 years.1

bTrial 3 was a 16-week, randomized, double-blind, placebo-controlled, parallel-group trial in 140 patients with CF age 12 years and older who were homozygous for the F508del mutation. KALYDECO is not effective in patients with CF who are homozygous for the F508del mutation in the CFTR gene.1

cTrial 4 was an 8-week, crossover design trial in 39 patients with a G1244E, G1349D, G178R, G551S, G970R, S1251N, S1255P, S549N, or S549R mutation. Trial 4 patients were between the ages of 6 and 57 years.1

dTrial 5 was a 24-week, placebo-controlled trial in 69 patients with an R117H mutation. Trial 5 patients were between the ages of 6 and 68 years.1

eTrial 6 was a 24-week, open-label trial in 34 patients who could have had a G551D, G1244E, G1349D, G178R, G551S, G970R, S1251N, S1255P, S549N, or S549R mutation. Of the 34 patients enrolled, 32 had the G551D mutation and 2 had the S549N mutation. Trial 6 patients were 2 to <6 years of age.1

fTrial 7 was an 8-week crossover design trial involving patients between the ages of 12 and 72 years who were heterozygous for the F508del mutation and a second CFTR mutation predicted to be responsive to ivacaftor. A total of 156 patients were randomized to and received KALYDECO.1

gTrial 8 was a 24-week, open-label trial in a cohort of 19 patients age 12 months to <24 months, a cohort of 11 patients age 6 months to <12 months, and a cohort of 6 patients age 4 months to <6 months who could have a G551D, G1244E, G1349D, G178R, G551S, R117H (eligible for this study only in the US), S1251N, S1255P, S549N, or S549R mutation.1-4 

 

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