Summary of the 1/5/14 Vertex Investor Press Release & Conference

Kalydeco Growth
“In 2014, further growth and achievement of the companys total 2014 net product revenue guidance for KALYDECO is dependent on completion of reimbursement discussions in Australia and Canada for eligible patients with the G551D mutation and on the potential further expansion of the KALYDECO label globally.”

Slide 6

Kalydeco beyond G551D

Other Gating
The FDA recently approved Kalydeco with 8 gating mutations. Approx 150 people aged 6 years and older have these gating mutations in the US.
The outcome from the EMA application to expand the Kalydeco label to include the other gating mutations is expected mid year. Approx 250 people aged 6 years and older have these gating mutations outside the US, majority in Europe.

2-5 year old Gating
Phase 3 study fully enrolled, all patients have completed the dosing period
Primary endpoint is safety, secondary endpoints include pharmacokinetics, change in sweat chloride and change in weight
Data expected Q3 2014, potential FDA and EMA applications second half 2014
Approx 300 children aged 2-5 have a gating mutation in North America, Europe and Australia

– Vertex plan to submit an application to the FDA (mid year) and EMA (second half 2014) to expand the Kalydeco label to include patients aged 18 and older with R117H. 
– Approx 700 people aged over 18 have R117H in North America, Europe and Australia 

Residual Function
Phase 2 study data expected Q2 2014
– “In our view, a successful result in this study of approximately 20 participants would lay the groundwork for pivotal studies of ivacaftor in patients with residual CFTR function”
– Vertex do not know yet “how many of all those residual functions are going to be responsive to KALYDECO”
More than 3000 people have a non R117H residual function mutation in North America, Europe and Australia (aged 6 and older)


Phase 3 VX809 / Kalydeco Trials with F508del homozygotes
– Dosing complete, d
ata expected mid year
Potential FDA and EMA applications in the second half of 2014
FDA requested the endpoint swap (absolute FEV1 change is now a primary outcome measure and relative FEV1 change is a secondary outcome measure)
90% powered to detect an absolute improvement of 3% from baseline compared to placebo (the very large sample size makes it easier to reach statistical significance with a small FEV1 result, eg 3%)

The FDA recently granted VX661 Orphan Drug Designation

Phase 2 VX661 / Kalydeco Trial with F508del homozygotes
Dosing started, 12 week trial, 40 patients
– Evaluating safety, efficacy and pharmacokinetics

Phase 2 VX661 / Kalydeco Trial with G551D / F508del heterozygotes Results
– 28 day trial, VX661 was added to patients already taking Kalydeco
– Mean absolute improvement of 4.6% from baseline (statistically significant, p=0.012)
– Mean relative improvement of 7.3% (p=0.012)
– Mean reduction in sweat chloride of -7.02 mmol/L (p=0.053) 

Slide 9

Implications from these results
“For us, there are really 3 important takeaways: first, once again, in vitro data with our CFTR modulators has been predictive of a clinical benefit in the specific patient population; second, correctors like 661 appear to be clinically active on a single F508del allele; and lastly, these results suggest to us that treatment for heterozygous patients may be further enhanced with CFTR modulators that are tailored toward each allele.”

This means that 1) the lab data has been predictive of clinical benefit once again, 2) correctors appear to help a single F508del mutation and 3) that treatment for patients with two different mutations may be enhanced with specific medications for each mutation.

“Based on the data announced today, and pending data from the ongoing 12-week study in patients homozygous for the F508del mutation, Vertex plans to discuss with global regulatory authorities the potential approval pathway for VX-661 in combination with KALYDECO for people with CF who have the F508del mutation and another mutation known to respond to KALYDECO alone.”

65-70% of patients who have G551D, a gating mutation or residual function also have F508del.

Future Approaches
“We want to continue our leadership position in CF, and that’s going to come in 2 forms. One is to continue to develop our expanding portfolio of medicines, so not only 809 and 661 but next-gen correctors, which we think are going to be very important in both expanding the region, expanding the benefit. But the other thing is we have a very active, as you can imagine, ongoing surveillance program of all of the potential, other assets out there in CF. And we’ll continue to watch that and make sure that we’re either partnering, acquiring or doing whatever we can to get the best regimens we can in combination with our drugs.”

Sources: May 1 Investor Conference, May 1 Press Release, VX661 with G551D/F508del Press Release & Seeking Alpha Transcript


Join the conversation! 2 Comments

  1. Thanks for the fantastic summary!

  2. Thank you Gen


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1. Class 2 Mutations & F508del, 1. Class 3 Gating Mutations & G551D, 1. Residual Function Mutations & R117H, 3. Vertex - Kalydeco, 3. Vertex - VX809 & VX661