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Now Approved for Ages 2 Through 5 Years

ORKAMBI is a combination of lumacaftor and ivacaftor indicated for the treatment of cystic fibrosis (CF) in patients age 2 years and older who are homozygous for the F508del mutation in the CFTR gene.1

See the Clinical Trial Data for Patients Age 2 Through 5 Years

How to
Take ORKAMBI

See how to administer ORKAMBI oral granules and tablets.

View Dosing and
Administration Information

Professional
Resources

Browse helpful materials to support your practice and to access resources to share with your patients.

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Professional Resources

A Snapshot of
ORKAMBI Experience

6-11

Experience in Patients Age 6 Through 11 Years


~75%
Have Initiated2,a,b

~75% of patients (~1600) age 6 through 11 years in the US have initiated ORKAMBI as of April 30, 2018


~87%
Stayed on Therapy3,c

~87% of patients in the US age 6 through 11 years who initiated ORKAMBI remained on therapy as of April 30, 2018

At ~92% Compliance4,d

The median compliance for patients age 6 through 11 years in the US was ~92% (average compliance was ~84%) over a 6-month period ending April 30, 2018

aFigure does not reflect patients that discontinued treatment.
bThe population of patients age 6 through 11 years homozygous for F508del is estimated based on the CFF 2016 Patient Registry Annual Data Report, which may not include all such patients and reflects data captured through December 2016. The ORKAMBI initiation information is based on data from prescriptions received by Specialty Pharmacies captured through April 2018. These data did not include genotypes of patients.
cFigures based on data from prescriptions received by Specialty Pharmacies captured through April 30, 2018. These data did not include genotypes of patients.
dCompliance calculated using Proportion of Days Covered methodology over 6 months through April 30, 2018. Figures based on data from prescriptions received by Specialty Pharmacies captured through April 30, 2018. These data did not include genotypes of patients.

12

Experience in Patients Age 12 Years and Older


~91%
Have Initiated5,e,f

~91% of patients (~7600) age 12 years and older in the US have initiated ORKAMBI as of April 30, 2018


~39%
Stayed on Therapy6,g

~39% of patients in the US age 12 years and older who discontinued ORKAMBI reinitiated treatment as of April 30, 2018

At ~81% Compliance7,h

The median compliance for patients age 12 years and older in the US was ~81% (average compliance was ~75%) over a 6-month period ending April 30, 2018

eFigure does not reflect patients that discontinued treatment.
fThe population of patients age 12 years and older homozygous for F508del is estimated based on the CFF 2016 Patient Registry Annual Data Report, which may not include all such patients and reflect data captured through December 2016. The ORKAMBI initiation information is based on data from prescriptions received by Specialty Pharmacies captured through April 2018. These data did not include genotypes of patients.
gFigures based on data from Commercial Data Warehouse readout of ORKAMBI patient status as of April 30, 2018.
hCompliance calculated using Proportion of Days Covered methodology over 6 months through April 30, 2018. Figures based on data from prescriptions received by Specialty Pharmacies captured through April 2018. These data did not include genotypes of patients.

Important Safety Information

Use in Patients With Advanced Liver Disease

  • Worsening of liver function, including hepatic encephalopathy, in patients with advanced liver disease has been reported. Liver function decompensation, including liver failure leading to death, has been reported in CF patients with pre-existing cirrhosis with portal hypertension while receiving ORKAMBI. Use ORKAMBI with caution in patients with advanced liver disease and only if the benefits are expected to outweigh the risks. If ORKAMBI is used in these patients, they should be closely monitored after the initiation of treatment and the dose should be reduced

Indication

ORKAMBI® (lumacaftor/ivacaftor) is a combination of lumacaftor and ivacaftor indicated for the treatment of cystic fibrosis (CF) in patients age 2 years and older who are homozygous for the F508del mutation in the CFTR gene. If the patient's genotype in unknown, an FDA-cleared CF mutation test should be used to detect the presence of the F508del mutation on both alleles of the CFTR gene.

Limitations of Use

The efficacy and safety of ORKAMBI have not been established in patients with CF other than those homozygous for the F508del mutation.

Liver-related Events

  • Serious adverse reactions related to elevated transaminases have been reported in patients with CF receiving ORKAMBI. In some instances, these elevations have been associated with concomitant elevations in total serum bilirubin
  • It is recommended that ALT, AST, and bilirubin be assessed prior to initiating ORKAMBI, every 3 months during the first year of treatment, and annually thereafter. For patients with a history of ALT, AST, or bilirubin elevations, more frequent monitoring should be considered. Patients who develop increased ALT, AST, or bilirubin should be closely monitored until the abnormalities resolve
  • Dosing should be interrupted in patients with ALT or AST greater than 5 x upper limit of normal (ULN) when not associated with elevated bilirubin. Dosing should also be interrupted in patients with ALT or AST elevations greater than 3 x ULN when associated with bilirubin elevations greater than 2 x ULN. Following resolution of transaminase elevations, consider the benefits and risks of resuming dosing

Respiratory Events

  • Respiratory events (e.g., chest discomfort, dyspnea, and respiration abnormal) were observed more commonly in patients during initiation of ORKAMBI compared to those who received placebo. These events have led to drug discontinuation and can be serious, particularly in patients with advanced lung disease (percent predicted FEV1 (ppFEV1) <40). Clinical experience in patients with ppFEV1 <40 is limited, and additional monitoring of these patients is recommended during initiation of therapy

Effect on Blood Pressure

  • Increased blood pressure has been observed in some patients treated with ORKAMBI. Blood pressure should be monitored periodically in all patients being treated with ORKAMBI

Drug Interactions

Substrates of CYP3A

  • Lumacaftor is a strong inducer of CYP3A. Administration of ORKAMBI may decrease systemic exposure of medicinal products that are substrates of CYP3A, which may decrease therapeutic effect. Co-administration with sensitive CYP3A substrates or CYP3A substrates with a narrow therapeutic index is not recommended
  • ORKAMBI may substantially decrease hormonal contraceptive exposure, reducing their effectiveness and increasing the incidence of menstruation-associated adverse reactions, e.g., amenorrhea, dysmenorrhea, menorrhagia, menstrual irregular. Hormonal contraceptives, including oral, injectable, transdermal, and implantable, should not be relied upon as an effective method of contraception when co-administered with ORKAMBI

Strong CYP3A Inducers

  • Ivacaftor is a substrate of CYP3A4 and CYP3A5 isoenzymes. Use of ORKAMBI with strong CYP3A inducers, such as rifampin, significantly reduces ivacaftor exposure, which may reduce the therapeutic effectiveness of ORKAMBI. Therefore, co-administration with strong CYP3A inducers is not recommended

Cataracts

  • Cases of non-congenital lens opacities have been reported in pediatric patients treated with ORKAMBI and ivacaftor, a component of ORKAMBI. Although other risk factors were present in some cases (such as corticosteroid use and exposure to radiation), a possible risk attributable to ivacaftor cannot be excluded. Baseline and follow-up ophthalmological examinations are recommended in pediatric patients initiating treatment with ORKAMBI

Adverse Reactions

  • Serious adverse reactions, whether considered drug-related or not by the investigators, that occurred more frequently in patients treated with ORKAMBI included pneumonia, hemoptysis, cough, increased blood creatine phosphokinase, and transaminase elevations. These occurred in 1% or less of patients
  • The most common adverse reactions in patients age 12 years and older in Phase 3 trials (Trials 1 and 2) occurring in ≥5% of patients treated with ORKAMBI (N=369) vs placebo (N=370) and at a rate higher than placebo were dyspnea, nasopharyngitis, nausea, diarrhea, upper respiratory tract infection, fatigue, respiration abnormal, blood creatine phosphokinase increased, rash, flatulence, rhinorrhea, and influenza
  • The safety profile in patients age 6 through 11 years from an open-label Phase 3 trial (Trial 3; N=58) and a placebo-controlled Phase 3 trial (Trial 4; patients treated with ORKAMBI, N=103 vs placebo, N=101) was similar to that observed in Trials 1 and 2. Additional common adverse reactions were reported in Trial 4, but were not reported in Trials 1 and 2. The adverse reactions in Trial 4 that occurred in ≥5% of patients treated with ORKAMBI with an incidence of ≥3% higher than placebo included: productive cough, nasal congestion, headache, abdominal pain upper, and sputum increased. The safety profile in patients age 2 through 5 years from an open-label Phase 3 trial (Trial 6; N=60) was similar to that in patients aged 6 years and older

Click here to access full Prescribing Information.

References:

1. ORKAMBI [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; August 2018. 2. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. VXR-US-20-02047(2); 2018. 3. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. VXR-US-20-02052(2); 2018. 4. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. VXR-US-20-02039(2); 2018. 5. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. VXR-HQ-88-00070(3); 2018. 6. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. VXR-HQ-20-00255(4); 2018. 7. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. VXR-HQ-88-00204; 2018.