Orkambi®

Question

Hello
Has an Orkambi® marketing study been scheduled for heterozygous F508del CF patients? (Excluding gating mutations).And in children under 12?
Can you send me the link of the site or sites that allowed you to answer me please?
How have other mutations been tested in phase 2? Per class? case by case?
Can we expect off-label use to allow precisely to assess the benefits of treatment in each case?
Thank you for your response.

Answer

Hello,

The marketing authorization for Orkambi® (combination of ivacaftor and lumacaftor) registered in the United States and Europe only apply to CF patients homozygous for F508del and 12 years of age or more. Clinical trials carried out in this population demonstrated statistically and clinically significant effects (though more modest than the effects obtained with the sole Ivacaftor in CF patients having at least one "gating mutation").

This product is not expected to have sufficient effect in heterozygous F508del CF patients (except if the F508del is associated with a gating mutation).

The extension of the marketing authorization to children under 12y will be considered depending on:
- efficacy and safety results observed in a daily life post-marketing study for the population over 12 years;
- and the results of a clinical trial targeted at children under 12y.

You will find below the link for the marketing authorization by the US Food and Drug Administration (FDA) of Orkambi® (ivacaftor + lumacaftor) for homozygous F508del patients 12 years and older:

www.bloomberg.com/news/articles/2015-07-02/vertex-wins-u-s-approval-for-cystic-fibrosis-combo-orkambi


Ivacaftor was tested for Class 3 mutations (gating mutations) through phase 2 and phase 3 studies. After studies of the main class 3 mutation (G551D), other class 3 mutations were tested in the same Phase 2 studies and phase 3. I have no reference to send to you about information that has been disseminated verbaly at medical congresses.
A priori prescriptions off-label can be considered:
- In respect of the indication submitted for marketing authorization (homozygous F508del patients 12 years and older)
- In an exceptional setting out prescription information presented in the AMM, in very critical situations without personal therapeutic solution and with the agreement of the laboratory by providing the product.

Hope this answer can help.
Best wishes
Gilles RAULT, MD, Roscoff CF Center

01.08.2015