A new study involving VX661 and Kalydeco is planned for the second half of 2013 with patients who have G551D and F508del. The in vitro data supports the addition of VX661 (see my June Vertex post: in vitro data shows that F508del/G551D heterozygotes improve from about 50% to 80% of normal function). This 4 week phase 2 study will include about 20 patients who are already receiving Kalydeco in the US and EU. Data is expected to be reported in late 2013 or early 2014.
About 80% of patients with G551D also have F508del.
During the vertex investor conference, it was asked why VX661 was being used instead of VX809: ‘As to the choice of 661, I would just say that VX-809 is in an extensive program, a Phase III program, with many, many studies. This is another opportunity for us to learn more about 661, and that’s why we chose it for the combination.’
2-5 year old G551D/Other Gating Mutations
Part 1 has been completed and a dose has been selected. Enrollment in the 4 week dosing part of the study is ongoing, results expected in the middle of 2014.
Other Gating Mutations
– Phase 3 study involved 39 participants who took Kalydeco for 8 weeks (crossover design)
– Mean absolute FEV1 improvement of 7.5% from baseline and 10.7% compared to placebo at 8 weeks (both p<0.0001)
– Statistically significant improvements seen with weight gain & the CFQ-R quality of life measure
– More data will be presented later this year
– Vertex plan to apply to the FDA and EMA later this year
– 400 patients worldwide have a gating mutation (not including G551D)
Results expected this year
Pending study results, Vertex expect to apply to the FDA early next year
Data from the n of 1 Denver study is expected in the first half of 2014
F508del homozygotes (2 copies F508del)
The phase 3 trial of VX809/Kalydeco has started and recruitment is going well. Vertex plan to report the data and submit an application to the FDA in 2014
‘In addition, we are planning to start a Phase II proof-of-concept study with the corrector, VX-983, pending the outcome of ongoing studies and discussions with regulators. The results from these Phase II studies with VX-661 and VX-983 will be important factors, as we consider which molecule to prioritize for further development as part of dual- or triple-combination regimens.’
F508del heterozygotes (1 copy F508del)
– Planning to start an 8 week phase 2 study with VX809/Kalydeco later this year
– 80 patients
– This study was requested by the FDA
Second Generation Correctors
‘We are also actively working to advance second-generation correctors that act on a different part of the CFTR folding process and could be used as part of the dual-corrector regimen, along with ivacaftor, to further enhance benefit for patients who are homozygous or heterozygous for F508del. Our goal is to bring a second-generation corrector into clinical development by the end of 2014.’
My June post has more information about the second generation correctors (Kalydeco, VX809 and a second generation corrector help homozygous F508del to reach about 45% of normal function).
– Kalydeco uptake in Europe has been very strong, now available in England, Scotland, Ireland, Northern Ireland and Wales. Nearly all eligible patients in the EU are taking Kalydeco.
– Revenue growth expected in 2014 (‘subject to the successful completion of reimbursement and regulatory discussions’) in both Australia and Canada
– Kalydeco was approved by the TGA in Australia earlier this month, this is the third largest market after the US and England, with 200 patients aged over 6 with G551D. Canada has 100 G551D patients aged over 6.
What does the breakthrough designation mean?
– More frequent interactions with regulatory authorities
– Trials have decreased from 48-52 weeks to 24 weeks
– Agreements about doses
– Accelerated by about 1.5 years
– Registration and approval is faster (US FDA process)