Kalydeco® and body height

Question

Dear expert team,
I have already wrote to you once concerning the off-label use of Kalydeco® with my son Till. He is taking now Kalydeco® for 10 weeks. He is 8-years old and has the mutation 1717 1G>A and the gating mutation S549R. Kalydeco® has a very good effect in him without negative side effects having occurred so far. After 10 weeks the FEV1 has increased from 106 to 127, he has gained 2 kg weight and the sweat value has decreased about 85 points!! (115 mmol to 30 mmol). These are in my opinion remarkable results that could not have been expected, from which one can conculde, that the chloride channel is functioning more or less normally. I assume, that these results did not solely occur due to the gating mutation, however, that this effect has also something to do with the interplay of both mutations.
Now to my question: my son is per defintion growth-restricted, at the age of 8 years he is only 120cm tall. His brother (non CF) is 2 years younger and practically of the same height. I conclude from this, that his reduced body height is due to the underlying CF. What is your opinion, does Kalydeco® have the potency to influence the body height positively under the mentioned values? I know, there are much greater problems in connection to CF and I "complain" in the meantime on a high level. In spite of this, I would be interested in the effect of Kalydeco® on the body height, especially because my son is suffering from his small stature. I have looked up already for hours in the internet, however could not find anything.
Many thanks for your answer

Answer

Dear father of Till,
I am very happy that your son responds so well to "Kalydeco®". To be fair, I have to mention at this point, that Kalydeco® is only licensed for the mutation G551D in Germany. The license for furthter mutations like G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P and G1349D has been given since the end of february 2014 in the USA. However, only very few patients (about 150 in the USA) profit from the advanced license. Nevertheless it is an enormous success for such patients.

Now to your question:
The growth of your son could indeed be influenced to a great extent by the illness of CF. At the moment, the body height is punctually on the 3rd percentile and therefore at the borderline area to hyposomia. For a better judgement, information about the height of the parents, and with that the prognostic final height, the pattern of growth so far and the age of the bones in the course of time has to be taken into account. As the later pubertal growth spurt contains in here the greatest growth potential, also the future development of the puberty is important.
About a therapeutical trial with growth hormone (GH), in general for a limited time interval, quite something has been published: growth and body height and also the lung function could be improved with this, especially in pre-pubertal patients. In spite of this, the usage of growth hormone without the proof of a real shortage is seen very critically. I recommend an endocrinological investigation after feedback from your CF center.
The second aspect of your question is interesting: could Kalydeco® influence the growth positively?
About this there is an analysis of the data from the studies Envision/Strive (Kalydeco® in comparison to placebo) in case of children, teenagers and young adults under the age of 20 with at least one mutation G551D:
Concerning the development of the weight an unambigously positive development could be observed. Concerning the body height an improvement could be observed in the group of the 6-11 year-olds. The statistical analysis concerning the body height shows a positive trend concering the growth under the therapy with Kalydeco® for 48 weeks (p=0.058).

Best regards,
Dr. Olaf Eickmeier

18.08.2014