October 20, 2013

October Vertex Update

Kalydeco: New data with G551D
Data from the PERSIST study showed that after 144 weeks of Kalydeco there was a durable treatment effect in FEV1, weight and other measures. Side-effects were consistent with previous studies. Data from the GOAL study showed a lower rate of hospitalisations, improved intestinal function and decreased bacterial colonisation.

Kalydeco Availability
Currently available in England, Scotland, Northern Ireland, Wales, the Republic of Ireland, France, Germany, the Netherlands, Austria, Denmark, Sweden, Norway, Greece and the US.

‘Vertex is in active discussions with relevant agencies in Australia and Canada regarding public reimbursement of KALYDECO in these countries.’

Kalydeco Label Expansion
1. Gating Mutations

– Application submitted to FDA (US) and EMA (Europe) for people with CF aged 6 and older with a non G551D gating mutation
– Approx 400 people have a non G551D gating mutation in North America, Europe and Australia (aged 6 and older)

2. R117H
– Phase 3 study is ongoing and fully enrolled, data expected by the end of 2013
– Potential FDA application early 2014 and EMA application in Q2 2014
– Approx 1100 people have R117H in North America, Europe and Australia (aged 6 and older)

3. 2-5 year old Gating Mutations
– Phase 3 study is ongoing and fully enrolled
– Data expected in Q2 2014, potential FDA application in Q2 2014
– Approx 300 children aged 2-5 have a gating mutation in North America, Europe and Australia

4. Residual Function Mutations
– Enrollment complete in the phase 2 study, data expected in Q2 2014
– More than 3000 people have a non R117H residual function mutation in North America, Europe and Australia (aged 6 and older)

VX809 Trials
1. Phase 3 VX809 / Kalydeco Trials with F508del homozygotes
– Enrollment complete, data expected mid 2014
– Vertex plan to submit an application to the FDA and EMA in the second half of 2014

2. Phase 2 VX809 / Kalydeco Trial (ages 6-11) with F508del homozygotes
Dosing complete in the pharmacokinetics part of the phase 2 study
Enrollment in the second part of the study expected Q1 2014
Data is expected to be used for ‘potential subsequent registration of the combination in children ages 6 to 11 in the U.S.’

3. Phase 2 VX809 / Kalydeco Trial with F508del heterozygotes
Includes participants aged 18 and older who have F508del and a second mutation not expected to respond to VX809 or Kalydeco alone
Enrollment has commenced in the 8 week study, involves 400mg VX809 twice daily and Kalydeco (250mg) twice daily
This study was requested by the FDA to guide labeling in the heterozygous population

VX661 Trials
1. Phase 2 VX661 / Kalydeco Trial with F508del homozygotes
– 12 week trial, enrollment expected Q1 2014 (following protocol approval)
This trial is needed to establish efficacy, safety and dosage in order to move the program forward. Likely to use VX661 in combination with Kalydeco and a second generation corrector: VX661 and VX809 work at the same part of the folding pathway, but VX661 is more potent and has less drug interactions than VX809.

2. Phase 2 VX661 / Kalydeco Trial with G551D / F508del heterozygotes
4 week study, currently enrolling, includes patients who are stable on Kalydeco
Investigating the effect of the addition of VX661 to Kalydeco in terms of FEV1
Data expected Q1 2014
During the investor conference it was mentioned that ‘VX661 could be combined with ivacaftor to further enhance the benefit in ivacaftor responsive patients’ (ie not just G551D) and when asked about FEV1 improvement, it was mentioned that ‘at least in the 10% or 20% range in order to really justify going forward’ (I think this refers to relative % change).

VX661 and VX983
Based on the emerging profiles for VX-661 and VX-983, Vertex has prioritized VX-661 over VX-983. The company does not intend to further develop VX-983.’

Second Generation Correctors
Vertex aim to bring a second generation corrector into trials by the end of 2014
. It is planned to use the second generation corrector with a first generation corrector and Kalydeco. The graphs below show that in the laboratory, F508del homozygotes reach about 25% of normal function with VX809 and Kalydeco, which increases to 50% with triple therapy (same as G551D with Kalydeco). F508del heterozygotes reach about 25% with triple therapy.

Future Approaches
Vertex plan to consider working with other companies in the future to enhance the benefit in CF patients.

Images from the Investor Conference:

Slide 4

Slide 12

Slide 13

Worldwide Populations
75,000 people with CF in the major markets:

US & Canada: 32,000, Europe: 40,000, Australia: 3000

1. G551D
More than 2,000 people with CF aged 6 and older have at least one copy of the G551D mutation in North America, Europe and Australia.
Currently treating nearly all patients in US/EU: quarterly revenue of $100 million dollars from Kalydeco. Additional growth opportunities in Australia and Canada (300 patients).

2. Mutations that may respond to Kalydeco
More than 7,000 people with CF, including those with the G551D mutation, have mutations that may respond to Kalydeco. Potential for annual revenue of $1-1.5 billion.
Over 50% of other gating patients are in Belgium, the Netherlands and Italy.

3. F508del
More than 28,000 people aged 6 and older have two copies of the F508del mutation in North America, Europe and Australia. This equals 22,000 aged over 12 and 6000 aged between 6-11. More than 17,000 people aged 6 and older have one copy of the F508del mutation and a second mutation not expected to respond to Kalydeco.

Slide 3

Slide 17

Slide 18

Sources: Vertex Press Release and October Vertex Investor Presentation


Join the conversation! 6 Comments

  1. Thank you for sharing all these updates with us! I have been reading your blog for a while now and you realy post interesting information about the new developments! Thank you for that! Keep it up! 🙂

    I was wonidering how you got access to the Vertex investor Presentation slides. Clicking on the source, it says you need to register? Did you do that?

    Thank you one again! 🙂

  2. Great summary Gen!

  3. Hello!

    I wondered if you might (please) provide some commentary on a couple of ddF508-relevant stories that have broken this year.




    the second article contains an incredibly juicy tit-bit… reporting that:

    “By combining Vertex VX-809 with chemical compounds that act as correctors on the domain containing the F508del mutation, the efficiency of the combination of drugs went up from 15 per cent to 60-80 per cent in cell culture models.”

    I wondered whether you might have insight into how/when/if the compounds identified in the two studies might advance into clinical trials? Thanks!


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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 - Second Generation Correctors, 3. Vertex - VX809 & VX661