Kaleydeco® off-label

Question

Dear expert team,
in the USA Kaleydeco® (active substance Ivacaftor) is already used "off-label". Patients report about positive experiences in spite of the fact that there is not the so-called celtic mutation underlying. What are the chances that one can receive in Germany the drug for the mutation deltaF508?
The market authorization process for the combination preparation after the termination of the 3rd test phase will for sure still last a longer time and I want to protect my children of unnecessary lung damage, insofar Kaleydeco® can even only approximatley have a positive influence on the course of the disease.
Many thanks in advance for the answer to my question.

Answer

Hello,
we received the following answer from Prof. B. Tümmler from Hannover:
"The sole administration of VX770 (Kaleydeco®) in case of F508del homozygous patients does not bring any clincal improvement. The study data has been published: [see below at *)]
Off-label use is only indicated by the physician in other gating-CFTR mutations, however not in case of class II mutations as F508del.
Best regards,
Burkhard Tümmler"

Yours sincerely,
Annette Pfalz für ECORN-CF

25.03.2013

*)
Chest. 2012 Sep;142(3):718-24.

Ivacaftor in subjects with cystic fibrosis who are homozygous for the
F508del-CFTR mutation.

Flume PA, Liou TG, Borowitz DS, Li H, Yen K, Ordoñez CL, Geller DE; VX 08-770-104
Study Group.

Department of Medicine, Medical University of South Carolina, Charleston, SC
29425, USA. flumepa@musc.edu

BACKGROUND: Ivacaftor (VX-770) is a cystic fibrosis transmembrane conductance
regulator (CFTR) potentiator that was approved in the United States for the
treatment of cystic fibrosis (CF) in patients ≥ 6 years of age who have a G551D
mutation; however, the most prevalent disease-causing CFTR mutation, F508del,
causes a different functional defect. The objectives of this study were to
evaluate the safety of ivacaftor in a larger population and for a longer time
period than tested previously and to assess the efficacy of ivacaftor in subjects
with CF who are homozygous for F508del-CFTR.
METHODS: This was a phase 2 study with a 16-week randomized (4:1), double-blind,
placebo-controlled period (part A) and an open-label extension (part B) for
subjects who met prespecified criteria.
RESULTS: Part A: The safety profile of ivacaftor was comparable to that of the
placebo. The overall adverse event frequency was similar in the ivacaftor (87.5%)
and placebo (89.3%) groups through 16 weeks. The difference in the change of FEV₁
% predicted from baseline through week 16 (primary end point) between the
ivacaftor and placebo groups was 1.7% (P = .15). Sweat chloride, a biomarker of
CFTR activity, showed a small reduction in the ivacaftor vs placebo groups of
-2.9 mmol/L (P = .04) from baseline through week 16. Part B: No new safety
signals were identified. The changes in FEV₁ or sweat chloride in part A were not
sustained with ivacaftor treatment from week 16 to week 40.
CONCLUSIONS: These results expand the safety information for ivacaftor and
support its continued evaluation. Lack of a clinical effect suggests that a CFTR
potentiator alone is not an effective therapeutic approach for patients who have
CF and are homozygous for F508del-CFTR.
TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00953706; URL:
www.clinicaltrials.gov.