in the more common patient type, the delta F508s, but they decided to start with this group because they figured the odds would be best.
They did a Phase 2 test in G551Ds, which showed a dramatic improvement in the sweat test. This was incredibly exciting, because there is no treatment—ever—that has been able to change the sweat test. The sweat test is a measurement of the underlying protein abnormality. Also, it showed an improvement in lung function. And it showed a change in the nasal potential difference, which is another measure of the channel, the ion channel. We measure voltage transfer across nasal passages. So the sweat test, and the nasal potential difference, are both measures of the protein function. And both of those changed with VX-770. That, and the fact that the drug is safe and easily absorbed and so forth, is the reason that it’s encouraging.
X: So you saw an alignment between fixing the underlying biological problem, and the clinical outcome? It’s rational.
BR: Absolutely. The whole thing makes sense. The other time I felt like this, way back over a decade ago, was when we developed the inhaled tobramycin [treatment]. It all made sense. The drug killed the bugs. The lung function got better. It was a similar situation. We had seen in Phase II what we thought we’d see. Fortunately we saw the same thing in Phase III and the drug got approved. So we’re hoping the same thing will happen here. If they can just show again what they showed in Phase II, that will be a strong message.
X: We hear a lot from biotech companies, in the downturn, increasingly turning to disease foundations like the CF Foundation and others for help in development. Why does this model make sense, and what makes for a good partnership?
BR: The reality is that while CF is one of the more common rare diseases, it’s still a rare disease. In the past—and I will say this is changing, because somebody like Vertex could potentially be very profitable here—traditionally, big companies like Pfizer or GSK didn’t want to touch rare diseases. There’s just not a big enough market. With something like this, where else are you going to use it besides with CF? If you’re developing a blockbuster, you want to be able to use it for multiple indications, or across millions of people. The only way rare diseases could really attract a company to work in this area would be to go to them and say, ‘We’re going to reduce every possible barrier you might have.’ So we take the financial risk early on. We let you get a profit later. As long as we get the drug. And we’ll have a system set up so that you can get access to the patients.
There are two big risks that companies have. There’s the financial risk upfront. But second of all, they need to get patients enrolled in studies so they can get their drug approved. There are many barriers to doing trials in a pediatric population, because they’re a vulnerable population. But I think that with rare diseases, the families are more motivated to get treatments. They sign up for studies.
But that’s largely because the CF Foundation has done a huge job of putting together this clinical trial network called the Therapeutics Development Network which we run. There are 77 sites now around the country. That means the doctors, and nurses, and researchers are all very well trained in how you conduct trials. The other thing the foundation has done is set up a huge national education effort for families. It’s set up to explain to them why they need to participate in research. How do you tell whether a research study is a good study, or one that’s worthless? The program is called “I am the key.” They have all this education material to get families to enroll.
X: How has that played out in the Phase III trial for Vertex?
BR: Everybody knows within the network who the patients are. They are all being followed in the clinic. It’s not like a hypertension trial, where you go out and put ads in the newspapers and hope people start coming in. This is a very captured audience. But, it’s a tiny audience. So each center will only have
