Thursday, February 24, 2011

VX-770 isn't the cure, but it's progress

Yesterday, the CF community was abuzz with the newly released clinical trial results for Vertex's VX-770. I received an email that summed up the findings:
"The data meet and exceed what we could have hoped for. Patients with the G551D mutation being treated with VX-770 showed:

- A significant improvement in lung function;
- A significant reduction in sweat chloride to below the diagnostic level for CF;
- Fewer pulmonary exacerbations;
- Patient-reported reduction in respiratory symptoms (wheezing, cough, congestion);
- Improved weight gain; and
- No safety issues.

The next step is the submission of a New Drug Application (NDA) to the FDA during the latter half of this year--with the hope of drug approval sometime in 2012."
So what does this mean? Is VX-770 a cure?
Unfortunately, no. Although VX-770 works (so far) to reduce the symptoms of the disease in people with the G551D mutation, it isn't a cure. Ronnie Sharpe got to be in on a conference call from the CF Foundation and Vertex regarding yesterday's announcement. He explained it this way on Facebook: "There was no indication . . .  that we are anywhere close to developing a pill that will eliminate all other treatments." Breck Gammel, another CF mom, blogged a whole summary of the call which I think anyone would LOVE to read. (Breck and Ronnie, I am so jealous you got to be in on it!)

To understand what VX-770 does, we have to step back and do a little CF cell biology--and I promise I won't get too technical.
  1. People with CF have two copies of faulty instructions in their genes.
  2. These faulty instructions tell mucus-producing cells to make the CFTR protein incorrectly.
  3. The normal CFTR protein goes up into the cell membrane and acts as a gateway. It lets chloride (salt) and water pass through, thus producing thin, slippery mucus that lines our lungs, sinuses, digestive organs, etc.
  4. When the CFTR protein is made incorrectly, the gateway doesn't function, and so people with CF produce thick, sticky mucus outside the cell wall.

So what does VX-770 do? According to the CF Foundation, this little blue pill "is designed to allow CFTR proteins located at the cell surface to function correctly and improve the flow of salt and fluids in and out of the cell." A CF mom on Cystic Life explained: It's "like WD40 to open a rusty gate....the reason G551D is targeted is because their [proteins] are [already in position] and just need help."

What is the G551D mutation?
There are lots of different ways that the CFTR protein can be created incorrectly. Each of these different kinds of alterations is called a mutation. G551D is one mutation of CF and is actually quite rare. As mentioned previously, the CFTR protein in people with the G551D mutation is in the right place in the cell membrane, but the gateway doesn't open correctly. That's why VX-770, which opens the "rusty gate," makes such a huge difference to people with the G551D mutation. Our little friend Bryce has this mutation. If VX-770 is passed, he will have a drug that will significantly help his health and increase his lifespan. Yay!

What about Peter and other people with CF that don't have that mutation?
The most common mutation of CF is called ΔF508. Peter has two copies of this mutation. In ΔF508, three amino acids are deleted in the CFTR protein. This causes the protein to be shaped the wrong way, so the cell rejects and destroys the protein before it even gets to the cell wall.

G551D is a Class III mutation; ΔF508 is a Class II mutation

You might be interested in Amanda's post on the VX-770 trial results. I love how she explains the ΔF508 in light of the VX-770 news: "Like 80% of the CF population, I have a mutation that affects CFTR in a way that it gets labeled as 'trash' before it even tries to go to the cell surface. VX-770 will not work for me…at least not by itself."

Good news, though. Vertex is working on another medication (in phase 2 clinical trials) that attempts to move the defective ΔF508 protein to the cell wall. Hopefully this drug, called VX-809, in combination with VX-770 may actually make the CF protein work. But for now, we don't know. Ronnie says: "The 770/809 combo is still in Phase 2 testing and it may need to go through multiple phase 2's before even thinking about a phase 3. [Their] best guess was if everything went perfect for the combo, it wouldn't be until 2015 (at the earliest) that we'd see it on market."

Is there going to be a cure?
Even if VX-809 and VX-770 work perfectly, people with CF will not be cured. But it may move CF into the direction of being a managed condition instead of a life-threatening disease. To me, that's coming pretty close to a cure.

I would love for Peter to be healed entirely from this disease. I think about the miraculous healings recorded in the scriptures and wish that my son and I could have been there. But I have faith that Peter's future holds joy and adventure than we can imagine, and I'm excited for that future--with or without a cure.

More reading about VX-770:
The CFF and Vertex press releases:

New York Times article about VX-770:

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