Vertex Pharmaceuticals will begin testing a combination of VX-445, tezacaftor and ivacaftor as a potential treatment for people with cystic fibrosis (CF) in two Phase III studies.
The first trial will evaluate the combination in around 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 US.
The second will include around 100 CF patients who have two copies of the F508del mutation, the most common genetic form of the disease, and is also designed to support submission of an application for this subset in the US, Vertex said.
The move follows Phase II data showing that an improvement in ppFEV1 (percent predicted forced expiratory volume in one second) of 11 percentage points from baseline through week four of treatment, when VX-445 was given to CF patients with two F508del mutations already receiving tezacaftor and 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, the firm noted.
“The initiation of pivotal development for VX-445 marks important progress toward our goal of advancing two different next-generation triple combination regimens into pivotal development to allow us to bring the best regimen to people with CF,” said Jeffrey Leiden, chairman, president and chief executive Vertex.
“We recognise that many people with CF are awaiting the first treatment for the underlying cause of their disease, and I am pleased that we have been able to advance both VX-659 and VX-445 into pivotal studies.”
The company also unveiled safety and efficacy results for the once-daily potentiator, VX-561, when dosed as part of a triple combination regimen with a next-generation corrector (VX-659 or VX-445) and tezacaftor in Phase II studies of people with one F508del mutation and one minimal function mutation.
In these studies, mean absolute improvements in ppFEV1 of 12.2 and 11.7 and percentage points from baseline through week four of treatment were observed for the VX-659 and VX-445 triple combination regimens, respectively.
The once-daily triple combination regimens were generally well tolerated, and the majority of adverse events were mild to moderate in severity.
Vertex noted that it intends to carry out further dose-ranging for VX-561 “to support potential late-stage development of future once-daily triple combination regimens”.