Inaxaplin (VX 147) advances into phase III portion of adaptive phase II/III clinical trial for the treatment of APOL1-mediated kidney disease

The clinical trial is designed to assess the impact of inaxaplin on kidney function and proteinuria for people living with proteinuric kidney disease mediated by two variants in the APOL1 gene, known as AMKD. In addition, the trial has been expanded to include adolescents with AMKD ages 10 to 17 years.

Previously reported Phase IIa proof-of-concept data demonstrated that inaxaplin led to a statistically significant and clinically meaningful mean reduction in the urine protein to creatinine ratio (UPCR) of 47.6% at 13 weeks of treatment compared to baseline, providing the first clinical evidence that an oral small molecule APOL1 inhibitor can decrease proteinuria in people with AMKD.

“Inaxaplin, a first-in-class molecule that addresses the underlying cause of APOL1-mediated kidney disease, has already shown impressive results in the Phase IIa proof-of-concept study,” said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex. “Advancing this trial into Phase III and broadening the trial to include younger patients is a critical step forward in bringing this potential therapy to patients who are waiting.”

“AMKD is a rapidly progressing condition and often remains silent until the disease reaches an advanced stage. We have no approved disease-specific therapies for this truly devastating condition, and inaxaplin has the potential to transform the care of AMKD and significantly improve the lives of patients,” noted Glenn M. Chertow, M.D., M.P.H., Professor of Medicine, Stanford University School of Medicine, and Chair of Vertex’s APOL1 Program Steering Committee. “The kidney community is strongly encouraged by inaxaplin’s potential, which energizes those of us caring for patients with AMKD.”

An Independent Data Monitoring Committee (IDMC) reviewed blinded and unblinded Phase II safety and efficacy data from the Phase II/III pivotal trial, which evaluated two different doses of inaxaplin compared to placebo for 12 weeks of treatment in patients ages 18 to 65 years and recommended the selection of a single inaxaplin dose of 45 mg once daily in the Phase III portion of the Phase II/III study. The IDMC also recommended enrolling adolescents with AMKD ages 10 to 17 years in the Phase III portion of the study.

About the Phase II/III AMPLITUDE Study: Inaxaplin is a potential first-in-class, investigational small molecule inhibitor of APOL1 with the goal of targeting the underlying cause of APOL1-mediated kidney disease (AMKD). The primary efficacy endpoint for the final analysis is estimated glomerular filtration rate (eGFR) slope in patients receiving inaxaplin compared to placebo. The secondary efficacy endpoint is time to composite clinical outcome, which will also be assessed at the final analysis and is defined as a sustained decline of greater than 30% from baseline in the eGFR, the onset of end-stage kidney disease or death. The final study analysis will occur when subjects have at least two years of eGFR data and when approximately 187 composite clinical outcomes have occurred. The study is also designed to have a pre-planned interim analysis at Week 48 evaluating eGFR slope, supported by a percent change from baseline in proteinuria in the inaxaplin arm versus placebo. If positive, the interim analysis may serve as the basis for Vertex to seek accelerated approval of inaxaplin in the U.S. for patients with AMKD.