SYMDEKO® (tezacaftor/ivacaftor and ivacaftor) is indicated for the treatment of patients with cystic fibrosis (CF) age 6 years and older who are homozygous for the F508del mutation or who have at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to tezacaftor/ivacaftor based on in vitro data and/or clinical evidence.

Safety data from 3 placebo-controlled clinical trials1

  • The overall safety profile is based on data from three double-blind, placebo-controlled Phase 3 clinical trials: 2 parallel-group trials of 12- and 24-week duration and one cross-over design trial of 8-week duration. Eligible patients were also able to participate in an open‑label extension safety study (up to 96 weeks of SYMDEKO)

  • In the three placebo-controlled Phase 3 trials, a total of 496 patients with CF aged 12 years and older received at least one dose of SYMDEKO

  • The proportion of patients who discontinued study drug prematurely due to adverse events was1:

1.6% OF PATIENTS
TREATED WITH SYMDEKO
2.0% OF PATIENTS
TREATED WITH PLACEBO
  • The safety profile of SYMDEKO was generally similar across all subgroups of patients, including analysis by age, sex, baseline ppFEV1, and geographic regions

  • There were no deaths in the placebo-controlled studies, and one death in the open-label extension study due to respiratory failure and influenza infection in a patient who had discontinued SYMDEKO 7 weeks prior, which was not considered to be related to the study drug by the investigator1,2

Laboratory abnormalities: Transaminase elevations1

Incidence of maximum transaminases during placebo-controlled trials1

Elevated ALT or AST SYMDEKO Placebo
>3 x ULN 3.4% 3.4%
>5 x ULN 1.0% 1.0%
>8 x ULN 0.2% 0.4%
  • The incidence of transaminase elevations was similar between treatment groups

  • One patient (0.2%) on SYMDEKO and 2 patients (0.4%) on placebo permanently discontinued treatment for elevated transaminases

  • No patients treated with SYMDEKO experienced a transaminase elevation >3 x ULN associated with elevated total bilirubin >2 x ULN

Cataracts1

  • Cases of non-congenital lens opacities have been reported in pediatric patients treated with SYMDEKO, as well as with ivacaftor monotherapy. Baseline and follow-up ophthalmological examinations are recommended in pediatric patients initiating treatment with SYMDEKO

Serious adverse reactions1

  • Serious adverse reactions, whether considered drug-related or not by the investigators, that occurred more frequently in patients treated with SYMDEKO compared to placebo included distal intestinal obstruction syndrome, 3 (0.6%) SYMDEKO-treated patients vs. 0 placebo patients

Most common adverse reactions1

Incidence of adverse reactions in ≥3% of patients taking SYMDEKO and greater than placebo (EVOLVE [Trial 1] and Trial 3*)1

Adverse Reactions
(Preferred Term)
SYMDEKO (N=334)
n (%)
Placebo (N=343)
n (%)
Headache 49 (15) 44 (13)
Nausea 29 (9) 24 (7)
Sinus congestion 13 (4) 6 (2)
Dizziness 12 (4) 8 (2)
  • The safety profile for patients with CF enrolled in EXPAND (Trial 2) was similar to that observed in EVOLVE and Trial 31

Trial 3 was a two-arm study that compared SYMDEKO to placebo in patients with CF aged 12 years and older who were heterozygous for the F508del mutation and had a second CFTR mutation not responsive to SYMDEKO. This study was terminated following the planned interim analysis because the pre-specified futility criteria were met.

Rates of respiratory adverse events3,a

11.3% OF PATIENTS
TREATED WITH SYMDEKO (N=56)
14.7% OF PATIENTS
TREATED WITH PLACEBO (N=74)

Pooled analysis of respiratory events3,a

Respiratory Events SYMDEKO (N=496)
Patients with events, n (%)
Placebo (N=505)
Patients with events, n (%)
Dyspnea 30 (6.0) 36 (7.1)
Respiration abnormal 15 (3.0) 20 (4.0)
Wheezing 9 (1.8) 13 (2.6)
Asthma 4 (0.8) 6 (1.2)
Chest discomfort 3 (0.6) 3 (0.6)
Bronchospasm 2 (0.4) 4 (0.8)
Bronchial hyperreactivity 0 0

aData pooled from EVOLVE (Trial 1), EXPAND (Trial 2), and Trial 3.1

Patients with severe lung dysfunction (ppFEV1 <40)1

  • EVOLVE (Trial 1) and EXPAND (Trial 2) included a total of 39 patients treated with SYMDEKO with ppFEV1 <40 at baseline (range 30 to 40)
    • In EVOLVE, 23 patients treated with SYMDEKO and 24 placebo-treated patients had ppFEV1 <40
    • In EXPAND, 16 patients treated with SYMDEKO, 15 placebo-treated, and 13 ivacaftor-treated patients had ppFEV1 <40
  • The safety profile in this subgroup was comparable to the overall results observed in both EVOLVE and EXPAND

ALT, alanine transaminase; AST, aspartate transaminase; ppFEV1, percent predicted forced expiratory volume in 1 second; ULN, upper limit of normal.