Vertex Pharmaceuticals Incorporated has announced that the US Food and Drug Administration (FDA) has approved Kalydeco (ivacaftor) for use in people with cystic fibrosis (CF) ages 2 and older who have one of 23 residual function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This precision medicine decision is based on analyses of in vitro data and is supported by more than five years of real-world clinical data that demonstrate Kalydeco's strong safety and efficacy profile. More than 900 people ages 2 and older in the US have one of these mutations. Based on this approval, Vertex increased its guidance for 2017 product revenues of Kalydeco to a range of $740 million to $770 million.

In addition to the mutations added to the label today, Vertex is continuing discussions with the FDA concerning the approval for additional people who have mutations responsive to Kalydeco, including one of five "splice" mutations. These five mutations were evaluated as part of the previously disclosed phase 3 EXPAND study in which the Kalydeco monotherapy arm met its primary efficacy endpoint while being generally well tolerated. More than 600 people ages 2 and older in the US have one of these mutations.

"Five years ago, Kalydeco became the first medicine to treat the underlying cause of CF. Since then, we have continued to invest in studies to improve the understanding of how this important medicine may benefit others with this serious and life-shortening disease," said Jeffrey Chodakewitz, M.D., executive vice president and chief medical officer at Vertex. "We are encouraged by the FDA's willingness to explore innovative ways to make highly effective medicines like Kalydeco with a well-established safety profile available to more people who are in urgent need. We will continue to work closely with the FDA to bring Kalydeco to more people with responsive mutations who are still in need as rapidly as possible."

"CF treatment has advanced rapidly, but there is need for broader access to these important medicines and development of additional medicines remains urgent," said Patrick Flume, M.D., director of the Medical University of South Carolina Cystic Fibrosis Center. "The use of in vitro data to support this approval is an important step forward in making medicines like Kalydeco available to more patients, especially those with rare mutations."

Based on clinical data from numerous prior studies and a demonstrated in vitro response employing a well-established, analytically validated method, Kalydeco is now approved to treat people with CF ages 2 and older who have one of 33 mutations in the CFTR gene.

CF is caused by defective or missing cystic fibrosis transmembrane conductance regulator (CFTR) proteins resulting from mutations in the CFTR gene. The defective or missing proteins result in poor flow of salt (chloride) and water into and out of the cell in a number of organs, including the lungs.

Chloride transport is a marker of the function of the CFTR protein at the cell surface. As with the other mutations for which Kalydeco is approved, mutations covered under today's approval are known to have some CFTR protein at the cell surface and have shown in vitro increases in chloride transport in response to Kalydeco by at least 10 percent of normal over baseline. Similar to the R117H mutation for which Kalydeco was previously approved, these additional residual function mutations result in a moderate loss of CFTR chloride transport, and people with these mutations generally have progressive lung function decline and other complications of CF.

On March 28, 2017, Vertex announced positive results from a phase 3 study that evaluated tezacaftor/ivacaftor combination treatment in people who have one mutation that results in residual CFTR function and one F508del mutation. The study met its primary endpoint and the combination was generally well tolerated. Vertex plans to submit these data as part of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) and a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for the tezacaftor/ivacaftor combination early in the third quarter of 2017.