Summary of the latest Vertex Investor Conferences (Dec 2 and Jan 14) and Press Releases (Dec 19 and Jan 12)

Worldwide Availability of Kalydeco:
“KALYDECO is currently available to eligible patients in the United States, England, Scotland, Northern Ireland, Wales, the Republic of Ireland, France, Germany, the Netherlands, Austria, Denmark, Sweden, Norway, Greece, and Italy. KALYDECO is also approved in Australia and Canada, and Vertex is in active discussions with relevant agencies in these countries to expand access to KALYDECO for eligible patients through public reimbursement. There are approximately 300 people age six years and older who have the G551D mutation in Australia and Canada.”

Kalydeco beyond G551D

1. Other Gating Mutations
– The FDA accepted the application to expand the Kalydeco label to include those aged 6 or older with other gating mutations

Under priority review, target date March 27, 2014
– EMA application submitted
– Approximately 400 people ages 6 years and older have other gating mutations in North America, Australia and Europe.

2. R117H Phase 3 Trial Results
Overall mean absolute FEV1 change of 2.1% (p=0.2), mean relative FEV1 change of 5.0% (p=0.06) (n=69), study did not meet primary endpoint
– Patients 18 years of age and older (n=50) had a mean absolute change of 5.0% (p=0.01) and a mean relative change of 9.1% (p=0.008)
– Vertex plans to meet with the FDA in early 2014 to discuss this data and a potential FDA application
Approx 1100 people have R117H in North America, Europe and Australia (aged 6 and older), approx 700 people are aged over 18 & approx 50% of R117H patients have an FEV1 below 90% and/or have significant symptoms in the US

3. 2 – 5 year old Gating Mutations
– Phase 3 study is ongoing and fully enrolled
– Data expected in Q2 2014, potential FDA submission in the second half of 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)

“These patients have normal or near normal pancreatic function or at least pancreatic sufficiency which suggests that they have CFTR at the cell surface, and we know from cell studies that they should respond to Kalydeco. The current trial is looking at different subsets of these residual function patients.”

VX809 Trials

1. Phase 3 VX809 / Kalydeco Trials with F508del homozygotes
– Enrollment complete
– The study involves 6 months of treatment, plus a follow-up visit one month later. The data then needs to be received and checked. Expecting to have the data mid 2014
– Vertex plan to submit an application to the FDA and EMA in the second half of 2014 (pending results)

The study is highly powered which means a small improvement in FEV1 (potentially 2-3% absolute) is likely to be statistically significant, p<0.05. This is due to the very large sample size. It is 90% powered to detect a 5% difference in FEV1 (I think this is relative change). There is a shorter window to see a difference in pulmonary exacerbations (6 months), however it is very highly powered to detect a difference between the intervention & placebo.

More than 28,000 people ages 6 and older have two copies of the F508del mutation in North America, Europe and Australia, including approximately 22,000 ages 12 and older.

2. Phase 2 VX809 / Kalydeco Trial (ages 6-11) with F508del homozygotes
Dosing complete in the pharmacokinetics part of the phase 2 study

“The second part of the study in children is expected to begin in the second half of 2014 and will be used for potential subsequent registration of the combination in children ages 6 to 11.”

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 either VX809 or Kalydeco alone
– 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)

“The study is designed to evaluate safety, efficacy and pharmacokinetics to characterize VX-661 for further clinical development. Vertex has submitted a protocol to the FDA for this study and expects enrollment to begin in the first quarter of 2014.”

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, enrollment complete
– Investigating the effect of the addition of a corrector with patients who are stable on Kalydeco
– Data expected in the first half of 2014

Second Generation Correctors
Several compounds are being investigated, hoping to have identified one and to have it in trials by the end of 2014. This timeline is unlikely to be accelerated.

The aim is to find a corrector which works at a different step in the folding pathway. This means that two steps in the folding pathway can be corrected when it is used in conjunction with a corrector such as VX661.

Future Approaches
– Research is a priority, $200 million is typically spent a year on research
– Potential to work with other companies/ technologies
– Strategy is to treat as many patients as possible and also to continue to raise the benefit

Unsure if approx 10% of the population can be reached with correctors and potentiators.
“If we could bring things in, which would enable us to try and potentially get to those 10% or 15% of patients that would clearly be something that we would be interested in.”

Sources: December & January Vertex Investor Presentations, January Press Release & December Press Release


Join the conversation! 1 Comment

  1. My daughter has both copies of DF508. Praying that the trials bear fruit .


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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