VX 445 + tezacaftor + ivacaftor combination for cystic fibrosis patients with a F508del mutation enters Phase III studies.- Vertex

Vertex Pharmaceuticals Incorporated announced that it is initiating two Phase III studies of VX 445, tezacaftor and ivacaftor as an investigational triple combination regimen for people with cystic fibrosis (CF). The first Phase III study will evaluate approximately 360 people with CF who have one copy of the F508del mutation and one minimal function mutation and is designed to support the submission of a New Drug Application (NDA) in the U.S. using data from the study�s 4-week primary efficacy endpoint together with safety data through 12 weeks of treatment.

The second Phase III study will evaluate approximately 100 people with CF who have two copies of the F508del mutation, the most common genetic form of the disease, and is designed to support the submission of an application for approval in patients with two copies of the F508del mutation in the U.S. using data from the study�s 4-week primary efficacy endpoint together with 24-week safety data generated from the Phase III study in patients with one F508del mutation and one minimal function mutation. The initiation of the study in people with two copies of the F508del mutation is supported by data announced from a Phase II study that showed an incremental mean absolute improvement in percent predicted forced expiratory volume in one second (ppFEV1) of 11.0 percentage points from baseline through week four of treatment when VX 445 (200 mg) was added in people with CF who have two F508del mutations and were already receiving tezacaftor in combination with ivacaftor. In the Phase II study, the VX 445 triple combination regimen was generally well tolerated, and the majority of adverse events were mild to moderate in severity.

Comment: Vertex plans Phase III trials of its next-generation correctors VX 659 and VX 445. They will be part of two triple combination therapy regimens that Vertex tests in CF patients. The combinations have the potential to treat patients with mutations that fail to respond to VX 661 (tezacaftor) or Kalydeco (ivacaftor).