) --Checking in from the 2012 North American Cystic Fibrosis Conference, where

Vertex Pharmaceuticals


presented more detailed data on the VX-809/Kalydeco combination therapy:

Wall Street came into Thursday's presentation seeking greater confidence that VX-809 and Kalydeco worked synergistically to improve lung function in cystic fibrosis patients with the common F508del mutation; and that 600 mg of VX-809 was the most effective dose to move forward into the phase III study. What investors feared was data previously undisclosed that would cast significant doubt on the future of the VX-809/Kalydeco program.

Mission accomplished, for the most part. The data presented were positive and largely in line with expectations, not perfect but without major red flags.

Vertex shares were essentially unchanged following the presentation, up 37 cents to $57.37.

The waterfall plot (see photo below) for 600 mg VX-809/Kalydeco patients showed a consistent treatment effect favoring the two-drug combination over placebo, with no outliers mucking up the results. Six of the 21 placebo patients showed lung function improvement (as measured by FEV1) between days 28-56 of the study compared to 14 of 20 patients treated with VX-809/Kalydeco.

From the start of the study through day 56, lung function for patients in the 600 mg VX-809/Kalydeco arm improved by 3.4% over baseline while lung function in placebo patients fell by 3.3%. The benefit favoring VX-809/Kalydeco over placebo started soon after combination therapy was initiated at day 28 and was clearly better by day 42.

You can't know for sure, but lung function curves presented Thursday suggest patients treated with 600 mg VX-809/Kalydeco had room for more improvement beyond 56 days. This bodes well for the phase III study, especially if Vertex decides to include a higher 800 mg dose of VX-809.

While the 600 mg VX-809 dose shined, the 200 mg dose (1.9% lung function improvement) outperformed the 400 mg dose (0.6% lung function improvement). Both the 200 mg and 400 mg doses of VX-809 outperformed placebo, but the lack of a dose response may raise concerns.

The data on sweat chloride reduction were also a bit confounding, with the 400 mg VX-809 dose outperforming both the 200 mg and 600 mg doses when the drugs were given as monotherapy for the first 28 days of the study.

Sweat chloride reductions for the 600 mg VX-809 dose were greater than the 200 mg dose.

The lack of correlation between sweat chloride and lung function improvement did not concern the study's lead investigator, Dr. Michael Boyle of Johns Hopkins School of Medicine, because sweat chloride is "just a biomarker" that is less clinically relevant than improvements in lung function.

On the safety side, six patients treated across all three doses of VX-809 during the one-month monotherapy stage discontinued due to adverse events. Reasons for discontinuation included rash and "chest tightness," according to Boyle, who was surrounded by Wall Street investors after his presentation.

"We're going to pay attention to that," said Boyle from the middle of the Wall Street scrum, referring to the adverse events observed in the trial. Boyle added that one of his patients reported "mild to moderate" chest tightness but it didn't cause her to drop out of the study.

"I viewed it as a sign that something was going on, probably a sign of an effect," he said.

In a separate interview, I asked Boyle for his overall impressions of the VX-809/Kalydeco data:

"Overall, I'm encouraged and excited. When I first got the

lung function averages, I said that's great but you can still hide a lot in averages. You can have one or two patients with an unexplainably large effect and not a lot of effect in most patients. But when I saw the waterfall plot and individual patient responses, and saw 55% of patients having what I consider a clinically significant improvement, that showed me that we have something here."

Dr. Steven Rowe of the University of Alabama, Birmingham and also an investigator in the VX-809/Kalydeco study, had a similar view:

"It's exciting to see the combination treatment come to fruition. It's a phase II design and we've been fooled before but this looks pretty convincing."

Rowe on what a 6% improvement in lung function means to a CF patient:

"FEV1 is a speedometer for CF patients. It's what they check every time they come to clinic and so, even small changes mean a fair amount to patients. These results compare favorably to many other drugs that have been approved and widely used for CF, so I think people would be excited about it."

--Written by Adam Feuerstein in Boston.

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