Regulators on both sides of the Atlantic are reviewing Vertex’ experimental tezacaftor/ivacaftor combination therapy for cystic fibrosis.

The therapy is being targeted towards patients with the condition who carry two copies of the F508del mutation, or one such mutation and one residual function mutation that is responsive to tezacaftor/ivacaftor.

The submissions include data from the 24-week, Phase III EVOLVE study, which evaluated the treatment in people who have two copies of the F508del mutation, and showed a mean absolute improvement in ppFEV1 (a measure of lung function) through 24 weeks of 4.0 percentage points from baseline compared to placebo.

The second Phase III study, EXPAND, looked at the combination in those carrying who have one mutation that results in residual CFTR function and one F508del mutation.

This also met the primary endpoints of absolute change in ppFEV1 from baseline to the average of the Week 4 and Week 8 measurements, with the tezacaftor/ivacaftor combination treatment demonstrating a mean absolute improvement of 6.8 percentage points compared to placebo and the ivacaftor monotherapy group demonstrating a mean absolute improvement of 4.7 percentage points compared to placebo.

Across both studies, tezacaftor/ivacaftor treatment was generally well tolerated, the most common adverse events -regardless of treatment group - being infective pulmonary exacerbation and cough.

In both studies, rates of discontinuations due to adverse events were low and similar between placebo and treatment groups (2.1 percent for placebo vs 1.7 percent for the tezacaftor/ivacaftor combination, as were rates of respiratory adverse events (15.0 percent for placebo vs 11.4 percent for the tezacaftor/ivacaftor combination).

In the United States, the tezacaftor/ivacaftor combination treatment has been granted Priority Review status, which shortens the FDA's anticipated review time from approximately 12 months to eight months.