State of research?

Question

Dear expert team,

How far advanced is the current state of research on VX809 really?

Is there a chance for this drug to be released to the market this year (2013)?

And is it correct that it is only applicable to the Delta F508 homozygous mutation – and only to patients in very bad general condition? (Which, if it were the case, one could not understand as a patient.)

What happened to Ataluren® – the results were insufficient – and so there is currently nothing in the pipeline for the R1162X stop mutation?

This means that the only drug currently on the market is Kalydeco® for the G551D mutation. Which is great!

I do think it is awesome that medicine has seen such major breakthroughs despite everything – but I am also worried – time is running out, particularly if one has two different mutations Delta F508/R1162X.

Many thanks for your answer.

Answer

Dear questioner,

Your assessment of the situation is correct – the development of a mutation-specific therapy for heterozygous carriers of F508del-CFTR is currently in the works, but not yet ready for release.

In short, the path from the newly discovered agent to the drug ready to be prescribed is as follows: preclinical testing -> phase-1 clinical trial -> phase-2 clinical trial -> phase-3 clinical trial -> approval procedure -> drug ready to be prescribed by doctors and available at pharmacies.

I am taking the current state of research on the drug VX809 from a Vertex press release of February 2013 (investors.vrtx.com/releasedetail.cfm?ReleaseID=743425 ; translations into German, Spanish, Dutch, French, and Italian are available on that site as well). The company is currently coordinating a so-called phase-3 clinical trial on a VX809/Kalydeco® combination therapy and expects (provided this phase-3 clinical trial will yield positive results) that the approval procedure can be initiated in 2014.

Parallel to this, two further Vertex therapeutics are in the developmental phase: VX661 and VX983. VX809, VX661, and VX983 are applicable to F508del. Even though Kalydeco® is only approved for G551D, it is currently being tested on F508del homozygous patients in combination with VX809 – with significantly better results than the previously tried single-drug therapy with VX809 only. For F508del heterozygous people (i.e., people like you, who inherited only one copy of the F508del CFTR gene), Vetex says: “In addition to the Phase 3 studies in people with two copies of the F508del mutation, Vertex plans to conduct an 8-week exploratory Phase 2 study of VX-809 in combination with ivacaftor in people 12 and older with one copy (heterozygous) of the F508del mutation on one allele and a second mutation that is not expected to respond to either ivacaftor or VX-809 alone. This study is designed to provide additional safety and lung function data on the combination in heterozygous patients, and will evaluate the twice daily (q12h) combination of VX-809 (400mg) and ivacaftor (250mg).” This means that Vertex wants to extend the application of VX809/ivacaftor to F508del heterozygous CF patients and expects adequate effort to plan a corresponding study. [Translator’s note: the following sentence in the original German answer relates to Germany only and was therefore omitted in the translation.]

The studies on VX661 and VX983 are not as far advanced yet – e.g. dosage determination and clarification of drug safety are only in phase 1 (VX983) or phase 2 (VX661). A combination therapy with Kalydeco® is currently being researched for both drugs. Again, this information is provided on Vertex’s web site: www.vrtx.com/research-development/pipeline. According to the company, 2014 will see a decision on which drug and/or which combination of drugs will be developed further (source: Vertex presentation slides from 2013, available online at sixtyfiverosesblog.wordpress.com/2013/04/28/april-vertex-update/).


In conclusion: a lot is happening, but you cannot yet get a prescription from your doctor. In evaluating the timeline, please note the source of information I chose – these are assessments from Vertex themselves. You noticed yourself that the earlier press releases on the VX809 agent were premature – the drug will not become available as a single agent, but there will presumably be an approval procedure for it as a combination therapeutic together with Kalydeco® next year.

Best regards,
Frauke Stanke

04.11.2013