Vertex Ivacaftor R117H Study Results -Fixes everything that CF breaks for this group

[CFParent2]

Is it just me or was this study poorly defined, providing misleading results?

I understand this was a difficult study to perform with so few participants, but it should have been tailored to the population.

They took patients under 12 who had FEV1 between 40 - 105% and patients above that age that had FEV1's 40-90%.

• Patients Ages 12 to 17: Two patients ages 12 to 17 enrolled in the study; one received placebo and one received ivacaftor. There were too few patients to make a statistical comparison in this age range.

????????????? 2 patients in this age group because, the rest had FEV1 levels that were too healthy to participate.

• Patients Ages 6 to 11: Seventeen patients ages 6 to 11 were enrolled in the study and had a mean baseline FEV[SUB]1 [/SUB]of 96 percent. In these patients, there was a mean absolute decline from baseline in FEV[SUB]1 [/SUB]of -2.8 percentage points (p=0.132) in patients who received ivacaftor (n=9) compared to a mean absolute increase from baseline in FEV[SUB]1[/SUB] of 3.5 percentage points (p=0.084) for those who received placebo (n=8). The mean absolute treatment difference was -6.3 percentage points (p=0.03).

?????????????? FEV1 of 96 percent baseline? What am I not understanding here? They tried to improve patients that are within 1 deviation of being statistically perfectly HEALTHY according to their FEV1 levels. How can anyone be surprised by these results? Why wasn't the sweat chloride test used as the first criteria for this age group. This is the GOLD standard when declaring them as having CF in the first place.

• Patients Ages 18 and Older: 50 patients ages 18 years of age and older were enrolled in the study and had a mean baseline FEV[SUB]1[/SUB] of 65 percent. In these patients, a pre-specified subgroup analysis showed a statistically significant mean absolute treatment difference of 5.0 percentage points (p=0.01). This corresponded to a mean relative treatment difference of 9.1 percent (p=0.008). An additional analysis was also conducted on FEV[SUB]1[/SUB] 4 weeks following the completion of treatment with ivacaftor. Mean lung function returned toward baseline in the patients who received ivacaftor, who showed a -3.1 percentage point (p=0.001) mean absolute within-group change from Week 24 to Week 28 (4 weeks after the end of treatment). Data on patients 18 and older are provided below:

In the group that had significant lung involvement and possibly enough people to make some type of statistical argument, showed significant improvement.


Other Findings:
It showed improvement for ALL ages for the sweat Chloride test. - DUH- that is because it works!
It showed no improvement in the number of pulmonary exacerbation
?????? Young R117H patients have few pulmonary exacerbations. Ours has only had 3 in his 18 years. The likelihood that they would have one in a 6 month period would be extremely low with or without the perfect cure. Probably even the oldest sickest patients do not go in for a tune up more than once or twice a year. How are you supposed to improve that over a 6 month trial?

The only reason it failed the primary endpoint, was that whoever was responsible did not research the background of the target population before defining the end criteria.

CF is a progressive disease, if people with given mutation are typically healthier and the disease takes longer to show involvement, the study needs to take that into account.

If my tires are not well aligned, I would not expect significant damage in the first 1,000 miles.. After 20,000 miles if I did not fix the problem, the adverse damage that occurred over the entire life of the tires would be obvious . I would never define a study that relied on the shape of the tires with only 1000 miles, to predict damage that is not measurable until 10,000.

I am upset with the way this study was defined. Hopefully the FDA and investors are smart enough to see that this drug works, for ALL ages. It fixes everything that is measurable broken by CF in-spite of the poorly defined study. This drug is a miracle for some of the CF population, hopefully poor science does not play a role in delaying it's release to those people.

http://investors.vrtx.com/releasedetail.cfm?ReleaseID=814799

 

[CFParent2]

More related info to the Vertex (Kalydeco) Ivacaftor R117H study

Did some additional research. I found a study of G551D with kids less than 12. Those kids had a mean baseline FEV1 of 84.2 ± 18.07 This is 11 percent worse than the kids in the R117H study. Not too surprising their reported FEV1 increase was 12% in the study. Their improvement brought them to the baseline FEV1 level of the R117H under 12 participants, who were basically healthy from the start.


Also found out that their Sweat Chloride numbers improved.

Sorry, if I have sounded critical, I am very thankfull to the CFF and Vertex for trying to expand the use of this drug to the R117H population. I am also very eager to see that the results are interpreted correctly, so the release of the drug can happen quickly, since it is obvious to me that it is effective.

REF:
http://clinicaltrials.gov/ct2/show/results/NCT00909727?term=vertex+and+cystic+fibrosis&sect=X105

 

[Gammaw]

It appears that Vertex has always been very approachable and helpful when members of the CF population called with questions about concluded studies. Have you tried calling and asking the same questions? Let us know if they give you answers! I've always assumed that one of the reasons they draw the line at 6 years old for many studies is because of the relative health of little ones which might confound results. . . .

 

[stranger]

I thought the grammar used in the study design was flawless...

While this seems frustrating, hopeless even... I think the context here to remember is that Vertex operates with a different set of rules that they have worked out with the FDA. Trying to apply older standards to something like this will likely yield to boiling blood.

It's worthwhile to refresh our memories that Vertex does not operate in a vacuum re: study design; the CFF, leading CF researchers all sit down at the table to craft up the design of the study. CFF (well, the CFFT arm of the CFF) also has skin in the game. Bob Beall is beyond passionate and has loads of credibility here.

I would encourage you to let this play out. I appreciated the detail & commentary you pointed out. It was very educational for me. Thanks!

 

[CFParent2]

Found a report that said the study failed?!!! Typical, the business people read the first line of a technical report and made false conclusions. The drug worked and still failed the primary endpoint.

Technical people need to be careful when defining a study so that it has a chance to show success in the main endpoint. To define the study correctly, it should not have allowed people in the study that had normal or above FEV1 levels. If this means that it only included 18yo+ patients so be it. To my knowledge fixing a cells operation to normal will not create above normal responses.

Hopefully, the powers that be will correct this soon, so I can stop being freaked out.


http://www.fiercebiotech.com/story/vertexs-kalydeco-flunks-phase-iii-cystic-fibrosis/2013-12-19

 

[CFParent2]

Talked with Vertex, they said they are still going to pursue FDA approval for Kalydeco. I asked a ton of questions but failed to ask how they were going to proceed and the time frame. I will let you know when I find out more.

 

[Gammaw]

Aha! Thanks for the update. I'm glad Vertex is maintaining their open lines of communication. I've always been impressed with the detail they will communicate to anyone willing to call and ask.