Cystic Fibrosis Overview - CFTR Modulator Therapies

Kalydeco (Ivacaftor)

These CFTR modulators are indicated for patients older than 4 months (KI)

Orkambi (Ivacaftor + Lumacaftor)

These CFTR modulators are indicated for patients older than 1 year (O-IL)

1. Symdeko (Ivacaftor + Tezacaftor) OR

2. Alyftrek (Deutivacaftor + Tezacaftor + Vanzacaftor)

These CFTR modulators are indicated for patients older than 6 years (S-IT or A-DTV)

Trikafta ( Ivacaftor + Tezacaftor + Elexacaftor)

This CFTR modulator is indicated for patients older than 2 years (T-ITE)

1. Homozygous (F508/F508) - 44.5% (mostly In females)

2. Heterozygous (F508/A455E) - 41.2% (mostly in males)

3. Gating (G55ID/ —) - 4.3% (females)

most common genetic variants are

Vanzacaftor, elexacaftor, tezacaftor, lumacaftor

These are class II CFTR modulator drugs, meaning they are “correctors” and are like taxi drivers - work by bringing protein to cell surface

Ivacaftor and Deutivacaftor (class III)

_____ are the only modulators that are a “potentiator” which actually causes CFTR protein to function properly (think enhances it!) 

half-life

The difference between Deutivacaftor AND Ivacaftor is the ______. DEUT is also a

1. Ivacaftor

2. Trikafta (ITE)

3. Alyftrek (DTV)

Three most effective CFTR modulators (in order)

Increasing FEV1 + BMI; Decreasing APE + Sx

CFTR modulators work by _______ and _______

• AST/ALT elevation 

• GI upset

• headache

• Mental health

Class adverse effects of CFTR modulators

• Take with FAT-CONTAINING FOOD

• Different formulations exist

• Short term and long term expectations

Counseling points for CFTR modulators

• LFTS q3 months upon initiation, then annually

• Annual eye exams

• Mental health 

How do we monitor CFTR modulators therapy?

CYP3A4 substrates / inducers

CFTR modulator DDI’s

At least one F508 mutation - causes significant effects on FEV1 and nutritional status

ETI was approved in 2019 for patients with

• no difference in FEV1

• Significant difference in sweat chloride

ETI trials showed:

• MAIN Goals of therapy are lung function AND nutrition

• ACT + meds improve lung function 

• CFTR modulators - treat underlying effect, improve lung function - just check for DDI’s 

Take home points for CFTR modulators/Overview of Cystic Fibrosis