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Vertex Planning NDA Filing for CF Drug in Patients with G551D Mutations for Second Half of 2011


Vertex plans to file a new drug application later this year for a cystic fibrosis drug that has shown better than expected results in patients harboring the G551D mutation.

After data from a Phase III trial, called STRIVE, yielded significant improvements in the lung function of study participants who received the investigational drug VX-770, Vertex said it would work with regulatory agencies in the US and abroad to speed the drug's approval.

According to Vertex, the company is targeting the second half of this year for a submission with US and European health regulators. "Due to the significance of these data [from STRIVE] and the great need for new, more effective medicines, we will work with regulatory agencies to determine the fastest way to get VX-770 approved for people with this specific type of CF," Peter Mueller, Vertex's chief scientific officer, said in a statement.

The company also reported results from another registration trial for VX-770, called DISCOVER, which tested the drug's safety in CF patients with F508del mutations. However, the improvement in lung function in patients treated with VX-770 was not statistically significant compared to those in the placebo arm.

STRIVE and DISCOVER are two out of three studies that need to be completed before the company can file for regulatory approval for VX-770. The last study, ENVISION, is slated for completion mid-year.

"The results from STRIVE are highly encouraging for the CF community and provide scientific evidence supporting our longstanding belief that targeting the underlying defect of CF may have a profound effect on the disease," Robert Beall, CEO of the Cystic Fibrosis Foundation, said in a statement.

Vertex and the CF Foundation jointly discovered the mechanism underlying VX-770. The foundation is funding Vertex's development of the drug and has provided $75 million to the company for CF research.

VX-770, a cystic fibrosis transmembrane conductance regulator potentiator, works by increasing the function of defective CFTR proteins by enabling their ability to transport ions across the cell membrane once they reach the cell surface. In CF patients with G551D mutations — the third most common CF-associated mutation — CFTR proteins on the cell surface don't function as they should. About four percent of CF patients carry the G551D mutation.

Vertex is also studying VX-770 with another drug, VX-809, a CFTR corrector, in patients with two copies of the F508del mutation. CFTR proteins don't reach the cell surface in people with the F508del mutation. It is estimated that 48 percent of CF patients have two copies of this mutation, while 39 percent have one copy of the F508del mutation.

Vertex did not respond to questions for this article.


In the 161-patient STRIVE study, Vertex compared patient outcomes on those receiving VX-770 to placebo. The 83 participants in the VX-770 arm achieved a 10.6 percent mean absolute improvement in lung function compared to those in the placebo group (n=78) over 24 weeks. The mean absolute improvement in those receiving VX-770 was 10.5 percent through 48 weeks of the study.

Additionally, those treated with VX-770 through 48 weeks were 55 percent less likely to experience pulmonary issues requiring antibiotics treatment, compared to the placebo-treated group. The VX-770-treated patients also had decreased sweat chloride, a marker of CFTR protein dysfunction, compared to those on placebo.

Those receiving VX-770 had 5 percent greater adverse events, such as headache, upper respiratory tract infections, nasal congestion, rash, dizziness, and bacteria in the sputum, compared to the placebo group. Most commonly reported serious adverse events, such as pulmonary exacerbation, were 13 percent in the VX-770 group versus 33 percent in the placebo group. One percent of patients in the VX-770 group experienced bloody coughing compared to 5 percent in the placebo group.

One percent of those in the VX-770 arm discontinued participation in the trial through 48 weeks, compared to 5 percent in the placebo group.

"Treating the underlying cause of cystic fibrosis with VX-770 led to clinical improvements that were far beyond our expectations, providing support for an entirely new approach to the treatment of this disease," Vertex's Mueller said in a statement. "All primary and key secondary outcome measures in this study supported VX-770 over placebo."


In addition to announcing data from STRIVE, Vertex also reported results from DISCOVER, a Phase II safety analysis of VX-770 in 140 patients with the F508del mutation. The majority of CF patients have at least one copy of this mutation.

In this study, the mean baseline lung function in those treated with VX770 was predicted to be nearly 80 percent compared to 75 percent in the placebo-treated group. "Results of the DISCOVER study showed that people treated with VX-770 achieved a mean absolute improvement from baseline compared to placebo of 1.6 percent through 16 weeks (p=0.25)," Vertex reported. This improvement was not statistically significant.

DISCOVER data further showed a 2 percent mean relative improvement in lung function from baseline through week 16, as well as a 2.9 mmol/L mean reduction in sweat chloride compared to placebo among those treated with VX-770. This improvement was "statistically significant, but small" with a p-value less than 0.04, Vertex said.

In this study, adverse events, such as cough, nausea, rash, and contact dermatitis, occurred more frequently in the VX-770 treatment group compared to placebo. "None of these events were serious or led to discontinuation of VX-770," Vertex said.

The company is planning to present data from the DISCOVER study at an upcoming medical meeting.

Additionally, the third registration study, ENVISION, is a trial involving VX-770 in children with CF who are between the ages of 6 years and 11 years and who have at least one copy of the G551D mutation. Data from this trial are expected in a few months.

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