Two Phase 3 Trials of Vertex’s Triple Combination Therapy with VX-659 Are Fully Enrolled

Vertex Pharmaceuticals has completed enrollment for two Phase 3 studies testing the triple combination therapy of its new CFTR corrector VX-659 together with tezacaftor (VX-661) and Kalydeco (ivacaftor) in patients with cystic fibrosis (CF).

The studies focus on patients with two F508del mutations in the CFTR gene (the gene that is defective in CF), or one F508del mutation plus one eligible minimal function mutation.

Vertex expects initial data from these two trials to be available in late 2018.

“The two Phase 3 studies of VX-659, tezacaftor and ivacaftor enrolled nearly 500 people with CF in less than five months, underscoring the significant interest within the CF community to advance triple combination regimens that have the potential to treat up to 90 percent of all people with the disease,” Reshma Kewalramani, MD, executive vice president of global medicines development and medical affairs, and chief medical officer at Vertex, said in a press release.

In the Phase 3 trial assessing patients with F508del mutation and one minimal function mutation (NCT03447249), 385 CF patients, age 12 and older, were enrolled. Patients will randomly receive either the triple therapy or a placebo.

The main result (primary endpoint) of the 24-week study is lung function improvement post-treatment, and will be reported as percentage change in the amount of air exhaled in one second (ppFEV1). Lung function will be assessed at baseline and after four weeks of treatment.

The trial will also assess key safety information (secondary endpoints), including changes in body mass index (BMI), sweat content, disease worsening (pulmonary exacerbation), and patient-reported outcomes.

The second Phase 3 ongoing trial (NCT03460990), assessing the triple combination with VX-659 in patients with two F508del mutations in the CFTR gene, recruited 111 CF patients age 12 and older.

In this study, all patients will receive a combination therapy of tezacaftor and ivacaftor for four weeks before the start of the triple combination regimen. After that, patients will be randomly assigned to receive either VX-659 or a placebo triple combination for the next four weeks.

The study’s primary endpoint is also a change in ppFEV1 from baseline to week 4 of treatment with the triple combination.

Vertex is also testing the efficacy of another experimental therapeutic candidate, VX-445, as a triple combination therapy with tezacaftor and ivacaftor in two separate clinical trials for CF patients with F508del mutation and one minimal function mutation (NCT03525444), or those with two F508del mutations (NCT03525548).

The trial design for these Phase 3 studies is similar to the VX-659 triple combo trials.

Enrollment for the VX-445 combo regimen studies is ongoing and expected to be completed by the end of 2018.

Vertex expects interim analysis data on these studies at the beginning of 2019, and hopes that information gathered from the VX-659 and VX-445 trials will help pinpoint the best triple combination regimen as a potential therapeutic option for CF. It expects that data will be used support a request for approval of a triple therapy to the U.S. Food and Drug Administration (FDA)  and regulatory agencies elsewhere.

“Our goal is to bring the best triple combination regimen to people with CF as quickly as possible, and we look forward to obtaining data later this year and in the first quarter of 2019 to support a submission for potential approval of a triple combination regimen,” Kewalramani said.

Additional safety and efficacy data from the VX-659 and VX-445 Phase 3 studies will be shared toward the end of 2019, when the studies are expected to be completed, the company said.