Vertex Pharmaceuticals Incorporated announced that, in a Phase 2 proof-of-concept (POC) study in patients with APOL1-mediated focal segmental glomerulosclerosis (FSGS), VX-147 on top of standard of care achieved a statistically significant, substantial and clinically meaningful mean reduction of 47.6% in the urine protein to creatinine ratio (UPCR) at Week 13 compared to baseline. VX-147 was well tolerated. These results provide the first clinical evidence and POC that an oral small molecule APOL1 inhibitor can decrease proteinuria in patients with APOL1-mediated kidney disease. Based on these results, Vertex plans to advance VX-147 into pivotal development in APOL1-mediated kidney disease, including FSGS, in First Quarter 2022. A total of 16 patients were enrolled in the study. According to the pre-specified statistical analysis plan, three patients who were noncompliant with treatment were not included in the primary efficacy analysis. In the 13 evaluable patients, treatment with VX-147 on top of standard of care resulted in a rapid, statistically significant and clinically meaningful mean change in proteinuria from baseline of -47.6% (95% CI: -60.0%, -31.3%) following 13 weeks of treatment. Reduction in proteinuria was observed early and continued throughout the 13-week treatment period. Results were consistent regardless of baseline proteinuria or background therapy. There were no treatment discontinuations due to adverse events (AEs), and there were no serious adverse events considered related to study drug. All AEs were mild or moderate in severity. The most common AEs (occurring in > 15% of subjects) were headache, back pain and nausea. About the VX-147 Phase 2 Study: The Phase 2 open-label, single-arm study evaluated the efficacy, safety and pharmacokinetics of VX-147 in patients with APOL1-mediated FSGS. Patients with biopsy-confirmed FSGS, two APOL1 genetic variants, proteinuria defined by at least 0.7 g/g in the UPCR and an estimated glomerular filtration rate (eGFR) of at least 27 mL/min/1.73 m2 were eligible for enrollment in the study. Patients were on a stable standard-of-care regimen, which could include an angiotensin-converting enzyme (ACE) inhibitor, an angiotensin II receptor blocker (ARB), immunosuppressants and/or low doses of corticosteroids. Patients were treated with VX-147 for a total of 13 weeks. The primary endpoint was percent change from baseline in UPCR at Week 13. The secondary endpoints were safety and pharmacokinetics. In addition, there is a 28-day safety follow-up period after the last dose of treatment and an optional off-treatment follow-up period of up to 12 weeks after the last dose of treatment. The study is ongoing for these follow-up periods. About APOL1-Mediated Kidney Disease: APOL1-mediated kidney disease is a form of chronic kidney disease caused by variants of the APOL1 gene. Over 100,000 people in the U.S. and Europe have two APOL1 genetic variants and proteinuric kidney disease. People who inherit two risk variants in the APOL1 gene have a course of disease that is far more aggressive than in the absence of APOL1 genetic variants. Inherited APOL1 genetic variants cause kidney disease through a toxic gain of function, which leads to podocyte injury. This injury disrupts filtration, resulting in proteinuria and rapidly progressive kidney disease. Progressive kidney disease can result in dialysis, kidney transplant or death.