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.
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)
– 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)
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
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.
Vertex plan to consider working with other companies in the future to enhance the benefit in CF patients.
Images from the Investor Conference:
75,000 people with CF in the major markets:
US & Canada: 32,000, Europe: 40,000, Australia: 3000
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.
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.