Vertex® agent for 18 patients realistic?

Question

Dear expert team,

For some time now, I have been following Vertex® (via their website), who have successfully completed clinical trials for a mutation-based therapy for ca. 4% of CF patients with KalydecoTM. KalydecoTM was now approved in Europe as well on July 27. I am happy for the 1500 European patients. As for me, I am 42 years old, male, FEV1 55%, no Pseudomonas, 177cm, 56kg, no diabetes, no involvement of the liver, and otherwise pretty lively.

I now saw in the cftr2.org mutation database that, of 35312 registered patients, just 18 patients have my combination of mutations (dF508:405+1G->A).

Is it possible that one of the study agents is targeted at this rare 405+1G->A mutation class and that there is a prospective therapy for me as well?

Greetings.

Answer

Hello,

F508del is the most common mutation causing CF, and the other one you mention is very rare. Your case is therefore a combination of mutations with so-called heterozygosity (as opposed to homozygosity).

The current state of research is as follows: apart from KalydecoTM, which you mention, and which is a substance supposed to be effective in patients with at least one G551D mutation on at least one allele, all other currently active studies for now refer only to homozygous patients with an F508del/F508del mutation.

According to our current state of knowledge, there is nothing in the pipeline yet for the other CFTR mutation you have. However, everything that is effective for F508del would also be effective for you.

Kind regards
Dr. Christina Smaczny and
Dr. Frauke Stanke

13.08.2012