Steps to a Cure

Good news in the treatment world. Vertex pharmaceuticals has completed part 2 of the phase 2a clinical trial of their CF drug VX770. The new findings they unveiled recently are not earth shattering, they basically just reinforced the exciting news from part 1 of the study that they announced last March. That announcement was huge.

In part 2 of the trial, 19 CF patients were given one of two different doses of the drug or a placebo. The two differences in this study design were that participants took the drug for longer and some of them took a higher dose. Those who received the drug showed that the drug successfully fixed the faulty CFTR function. This is the same as in the first study. From the press release, "Based on the positive results from this trial, Vertex plans to work with global regulatory authorities, including the U.S. Food and Drug Administration, to move VX-770 forward in the approval process. The company is targeting the first half of 2009 to initiate a pivotal trial that could eventually lead to drug approval." I'm assuming that "pivotal trial" is a phase 3 trial. Why do they have to be so vague?

I'm actually a little disappointed by the release of the new results because it means something changed. As you can see from this description of the phase 2a trial, in part 1 of the trial they were looking for people with mutation G551D. This is the only mutation they tested on in part 1 of the trial. It says though that for part 2 of the phase 2a trial participants "must have the G551D, R117H, or 2789 + 5G" mutation. This lead us to believe that in part 2 of the phase 2a trial they were going to test the drug on people with mutations other than G551D. They included R117H in the list which is what Camden has.

Lo and behold, they have finished part 2 of the phase 2a trial and it appears they again only tested people with the G551D mutation. Did they change their mind about the study design? Maybe they couldn't get anyone with that mutation to sign up for the study. There is a phase 2b clinical trial set for 2009 so maybe the testing on other mutations will occur in that trial. We'll feel a lot better about this promising new treatment once they have tested it on someone with the same mutation as Camden.

Here's the questions no one seems to be answering online.

1) When will the drug be tested on patients with the R117H mutation? There was a lot of talk about how this mutation is very similar in behavior to G551D (i.e. the malformed protein localizes to the cell wall but cannot get though.) Are they still planning on testing it or are they going to push it all the way through to market before they try it on other mutations? Tests in the lab have shown that VX -770 increases cyclic-AMP-dependent chloride secretion in cell cultures of R117H just like it does with G551D. Bring on the human testing.

2) What does a drug like this actually mean to a patient with CF? I know that is a lot to ask and no one really knows the answer but I would think someone would be able to say whether or not they think this is essentially a cure or simply something to mitigate the effects of CF by a certain percentage, etc. It probably depends a lot on the patient and they still don't know and no one wants to speculate so I'll forgive this one.

3) How does it affect digestion? I know there is data about this out there. Lung function is not the only thing affected by the CF mutations. The patients saw a 10% or so increase in lung function in just two weeks and sweat chloride levels dropped to normal levels. What happened to their digestion? Did participants find they did not need as many enzymes? Did they get fewer stomachaches? Even though lung function was the primary concern of the study I would think it would be foolish of them to not ask questions about digestion since they have the opportunity. This would be one more measure of the effectiveness of the drug (and the better it performs the higher their stock price goes). They could to a simple test to measure levels of human elastase to see how the pancreas was responding. I find it baffling if they didn't bother to do this. Spare me the press releases written for investors and people with no understanding of biology or CF. Where are the nitty gritty results?