F508del heterozygous- first recognitional breakthrough?

Question

Hello,
did I get it right from the English that for the first time there has been a significant improvement in the usage combination VX-661 and KALYDECO® (Ivacaftor) in case of F508del heterozygous patients "with/independent" of G551D?
That sounds like a breakthrough for the heterozygous mutation F508del?
I am not very experienced yet in this field.
However try to clutch at every hopeful straw. Fixate first of all on preventive "full-value therapy".
My daughter (3 years) was diagnosed to suffer from CF in October 2013. The mentioned heterozygous variant with another defect. And in here there were no findings until April 2014.
In another paper I read, that one supposes that the combination of two molecular correctors and Kalydeco® will have until 2017 a high probability of success for the heterozygous mutation F508del?
Many thanks in advance for your feedback,

http://analysisreport.morningstar.com/stock/research?nav=no®ion=USA&culture=en_US&ProductCode=mle&symbol=VRTX

http://investors.vrtx.com/releasedetail.cfm?ReleaseID=844677

Best regards,
S.

Answer

Dear questioner,
Vertex "works" at the moment on several substances, besides the drug VX770 (also known under the name Ivacaftor or Kalydeco®) that is already licensed for patients with G551D, also the substances VX809, VX661 and VX983 are tested in studies with CF patients. After the results from the cell culture, VX809, VX661 and VX983 are suitable for F508del. Vertex shows the actual strategies under:
sixtyfiverosesblog.wordpress.com/2013/04/28/april-vertex-update/


Combination therapies with two drugs are in the testing phase (e.g. VX770+VX661), combination therapies with three drugs (e.g.VX770+VX661+VX809) have started to be thought about. For 2014 Vertex plans according to their own statement to focus on a combination of drugs for the performance of further studies. From the great number of combination therapies, that are tested actually in small pilot studies, we can conclude:

1. Vertex is planning a molecular therapeutical strategy for patients with F508del. Hereby the target group is F508del homozygous AND heterozygous F508del/other CFTR mutation, that is also advertised for the investors (e.g. Ihre www-Quelle der morningstar.com). 90% of CF patients would profit from such a drug.

2. The features of the drugs are not as convincing in the clinical testing phase as in the cell culture model - otherwise the drug would already be ready with a single substance. Conbination therapies are more complicated, as for each preparation and each combination an own dosage-effect correlation has to be found out.

3. Vertex assumes, that until 2014 the choice of the substances and until 2017 the questions for finding a dosage will be solved. This timely estimation is based on the experience of the company with the former successful drug developments.

For F508del-CFTR heterozygous patients it can be read concretely at Vertex (link: investors.vrtx.com/releasedetail.cfm?ReleaseID=743425, there the paragraph „Study in People with One Copy of the F508del Mutation“):"Vertex is planning additionally to the phase-3-studies with patients having two copies of the F508del mutation, an 8-week explorative study on VX809 in combination with Ivacaftor in patients older than 12 years with one copy (heterozygous) for the F508del mutation on one allele and another mutation, from which no positive effect of Ivacftor or VX809 can be expected as a monotherapy. The study design allows the collection of additional security- and lung function data under the treatment with the combination VX809 (400mg) and Ivacaftor (250mg) two times a day (every 12 hours)."
That means, that Vertex wants to expand the usage of VX809/Ivacaftor on F508del heterozygous CF patients and expects enough success, in order to plan the respective study. If patients are going to be recruited for such a study, this is for sure going to be announced on the pages of the German patient organization (Mukoviszidose e.V.; muko.info/forschung/klinische-studien/cf-studien-in-deutschland.html).


In summary: a lot of research is done about the therapy of F508del (also for heterozygous patients) and I share the optimism, that in the end the effort will bear fruit. However: statments about the time frame (2014 we are in...2017 we know) I do not judge to be reliable. Therefore it remains for you at the moment "only" the preventive "full-value therapy" - if you want additionally follow in detail the state of affairs concerning the development of drugs, it would be the best to turn directly to a study center, that is taking part in a Vertex study. On the pages of the German patient organization (muko.info/forschung/klinische-studien/cf-studien-in-deutschland.html) about the study with VX661 and VX770 (that is there listed under the abbreviation "VX11-661-101") you also find the study centers from Germany, that take part in these studies.

Best regards,
Frauke Stanke

28.07.2014