Inaxaplin (VX-147) Enters Phase 3 in APOL1 Kidney Disease Trial

Vertex Pharmaceuticals has announced that inaxaplin (VX-147) has moved forward to the Phase 3 stage of a comprehensive Phase 2/3 clinical trial focusing on APOL1-mediated kidney disease (AMKD). This advancement follows the selection of a 45 mg daily oral dose to be tested against a placebo, complementing the standard care regimen. The trial's objective is to evaluate the effects of inaxaplin on kidney function and proteinuria in individuals with AMKD, which is caused by two variations in the APOL1 gene. Notably, the trial has been expanded to encompass adolescents aged 10 to 17 years, broadening the potential patient demographic.

The decision to advance to Phase 3 was bolstered by Phase 2a proof-of-concept data, which indicated a significant reduction in urine protein to creatinine ratio (UPCR) by 47.6% after 13 weeks of treatment with inaxaplin. This reduction marks a pivotal milestone, as it is the first clinical evidence suggesting that an oral small molecule APOL1 inhibitor can effectively decrease proteinuria in AMKD patients.

Carmen Bozic, M.D., Vertex's Executive Vice President and Chief Medical Officer, highlighted inaxaplin's potential, stating that it addresses the root cause of AMKD and has shown promising results in the Phase 2a study. The progression to Phase 3 and the inclusion of a younger patient group are seen as crucial steps towards making this therapy available to those in need.

Glenn M. Chertow, M.D., M.P.H., Chair of Vertex’s APOL1 Program Steering Committee, emphasized the severity and rapid progression of AMKD, which often goes unnoticed until it reaches an advanced stage. Currently, there are no approved therapies specifically for AMKD, making inaxaplin a potentially transformative treatment that could greatly enhance patient care and quality of life.

An Independent Data Monitoring Committee (IDMC) has reviewed the Phase 2 safety and efficacy data, endorsing a 45 mg once-daily dose of inaxaplin for the Phase 3 trial and recommending the inclusion of the younger age group. Regulatory bodies such as the U.S. FDA and the European Medicines Agency (EMA) have granted inaxaplin various designations, including Rare Pediatric Disease Designation, Breakthrough Therapy Designation, Priority Medicines, and Orphan Drug status, underscoring the significance of this compound in addressing unmet medical needs.

The Phase 2/3 AMPLITUDE Study is designed with primary and secondary efficacy endpoints focused on estimated glomerular filtration rate (eGFR) and time to composite clinical outcome, respectively. An interim analysis at Week 48 is planned, which could pave the way for seeking accelerated approval in the U.S. if results are positive. The study is actively enrolling participants across over 200 sites globally.

AMKD, caused by APOL1 gene variants, affects approximately 100,000 individuals in the U.S. and Europe, leading to aggressive disease progression and severe outcomes such as dialysis, transplant, or death. Vertex, established in 1989 with a global presence, is dedicated to developing transformative medicines for serious diseases, including cystic fibrosis, sickle cell disease, and beta thalassemia. The company continues to innovate and advance research in various serious conditions, reflecting its commitment to scientific excellence and patient care.