I came across this FDA review a few months ago and it has been on my list to add here. I have copied two interesting images from the review and added information to make them easier to understand.

The first image shows the individual FEV1 change with each participant in the G551D phase 3 study (12 and older).

Individual FEV1 Change G551D Kalydeco

Click on the image to see a larger version. The red crosses are those on Kalydeco, the black crosses are those in the placebo group. I have added the writing in red to make it easier to read.

The second image shows that there is little correlation between change in FEV1 and change in sweat chloride (data from the phase 3 G551D trial aged 12 and older). This is from the FDA document: “There is little if any correlation between change in % predicted FEV1 and change in sweat chloride at 48 weeks in both treatment groups (Figure 11).”

As you can see in the image, the individual results vary significantly. Change in sweat chloride varied from an increase of about 7 points to a decrease of about 87 points. Change in FEV1 varied from about a decrease of 8% to an increase in 34%. I have circled three interesting results in red: One person decreased about 45 points with their sweat chloride, but dropped about 8% FEV1, and another decreased about 75 points with their sweat chloride but only gained about 4% FEV1 (bottom two in the left of the graph). There is also one person who gained 30% FEV1 whilst their sweat chloride decreased by about 8 points (top right of graph).

Change in FEV1 V Sweat Chloride G551D Kalydeco

Click on the image to see a larger version. The red crosses are those on Kalydeco, the black crosses are those in the placebo group. I have added the writing in red to make it easier to read.

My interpretation of this information is that if you are on Kalydeco, it is important to focus on how you feel, any symptom changes and your stability (FEV1, exacerbations etc), as the change in FEV1 appears to have minimal correlation with the change in sweat chloride.

The phase 2 study looking at Kalydeco with homozygous F508del is also mentioned in the FDA document, however all the data is grayed out.

Source: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203188Orig1s000StatR.pdf

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1. Class 3 Gating Mutations & G551D, 3. Vertex - Kalydeco