April 28, 2013

April Vertex Update

I just listened to the 18/4/13 Vertex Investor Presentation, which I have summarised below:

Current Trials:
– Phase 3 other gating trial is fully enrolled, data expected this year
– Phase 3 R117H trial is enrolling
– 2-5 year old G551D or other gating trial ongoing
– Residual function trial – goal to define the type of patients who may benefit from Ivacaftor (Kalydeco) monotherapy
– Phase 3 VX809/Ivacaftor trial with F508del homozygotes- enrollment currently occurring, patients starting relatively soon, potential for FDA application next year
– With all combinations they are working towards a goal of one pill, once a day

VX661 with F508del homozygotes (2 copies F508del):
– After 28 days VX661/Ivacaftor- 4.8% and 4.5% mean absolute FEV1 change from baseline versus placebo (100mg and 150mg VX661 groups). Both p=0.01, this is a strong statistically significant result
– Also described as a 9% and 7.5% relative FEV1 increase
– Rapid increase in FEV1 by day 14, consistent response to day 28 (plateau)
– Followed by a 28 day washout period where FEV1 returned to baseline
– 19/31 in the 100mg and 150mg group had a relative improvement of 5% or more
– Statistically significant drop in sweat chloride seen with VX661 and Ivacaftor, similar to the statistically significant drop seen with VX809/Ivacaftor of about 10 points
– VX809 and VX661 have had similar FEV1 results so far (VX809 600mg group had a 6.7% absolute and 9.2% relative improvement versus placebo)
– Change in FEV1 and sweat chloride are not correlated well, they are focussing on FEV1 as it is more clinically meaningful
– No drug interaction with Ivacaftor and VX661 (VX809 and Ivacaftor interact, hence why a higher dose of Ivacaftor is needed with VX809)

New first generation corrector:
– VX983
– Compared to VX809 and VX661, VX983 is in the same chemical class, has comparable activity in vitro and acts on same step in corrector pathway at the same place
– Different metabolism and different PK/PD profile compared to VX809 and VX661 (PK/PD affects timing/dosage), this may allow for different combinations
– Triple combination may be possible with VX661 and VX983 as these do not interact with Ivacaftor
– Recently completed a phase 1 study, second phase 1 study currently occurring,
– Phase 2 trial with Ivacaftor planned for the second half  of 2013, 28 day trial with homozygous F508del
– VX661 and VX983 are close in terms of the development timeline
– Vertex plan to prioritise one of these in 2014 for development in combination with Ivacaftor and/or potential dual corrector combination

Second Generation Correctors
– Aim to use triple combination therapy (one potentiator plus 2 correctors) -> maximise benefit in F508del patients
– Currently in pre-clinical stage, goal to progress at least one into clinical trials for F508del homozygotes and heterozygotes by the end of next year

Slide 11

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Source: April Vertex Investor Presentation (no longer available)

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Join the conversation! 2 Comments

  1. Hi! What does this mean exactly: “2-5 year old G551D or other gating trial ongoing.” Has the trial started? Thank you

    Reply

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Category

1. Class 2 Mutations & F508del, 1. Class 3 Gating Mutations & G551D, 3. Vertex - Kalydeco, 3. Vertex - Second Generation Correctors, 3. Vertex - VX809 & VX661