Cystic Fibrosis is caused by a genetic mutation which leads to the
production of thickened sticky secretions in organs with epithelial cell
linings, including the respiratory tract. Over time, lung infections
lead to airway destruction, respiratory failure and death. The
first-in-class CFTR modulator Kalydeco, a CFTR potentiator works to
restore the function of the mutated CFTR protein in patients with the
G551D gating mutation of CF, allowing an improved flow f salt and
fluids on the surface of the lungs.

Only around 4% of CF patients in the US have the G551D gating mutation,
and more studies are needed to help determine whether people with other
CF gating mutations might also be eligible for Kalydeco. Still, the
drug's approval has paved the way for a new class of therapies, which
offer a personalized treatment approach to patients and could be highly
profitable for its developers.

Vertex (News - Alert) is now developing a combination therapy of potential
first-in-class CFTR modulator lumacaftor (VX-809) with Kalydeco (VX-770)
for the treatment of CF patients who are homozygous for the F508del
mutation in the CFTR gene. The CFTR corrector, lumacaftor increases
trafficking of the defective CFTR protein to the cell membrane, where it
can exert its functions. The combination therapy is currently in Phase
III stage of development, and is expected to gain approval in 2014.

It is estimated that around half of all CF patients are homozygous to
the F508del mutation, and Vertex has also announced plans to explore the
lumacaftor/Kalydeco combination therapy in patients that are
heterozygous to the F508del mutation.