Vertex Kidney Disease Drug Proves its Worth in Phase II

Vertex Pharmaceuticals reported its Phase II proof-of-concept trial of VX-147 in patients with APOL1-mediated focal segmental glomerulosclerosis (FSGS). The drug hit a statistically significant and clinically meaningful decrease of 47.6% in the urine protein to creatinine ratio (UPCR) at Week 13 compared to baseline.

Based on the data, the company plans to move it into Phase III studies in APOL1-mediated kidney disease, including FSGS, in the first quarter of 2022.

FSGS is a severe kidney disorder caused by mutations in the APOL1 gene creating protein loss in the blood and leading to progressive loss of kidney function from scarring. Symptoms include high levels of protein in the urine, fatigue, swelling in the limbs, and weight gain. There are currently no approved treatments for the underlying cause of the disease.

FSGS is usually treated with high-dose steroids to control blood pressure and fluid levels, but they aren’t used for long because of severe side effects. Even with treatment, it usually progresses to kidney failure, which is treated with dialysis or a kidney transplant.

“VX-147 is the first investigational treatment targeting the underlying cause of APOL1-mediated kidney disease,” said Carmen Bozic, executive vice president, Global Medicines Development and Medical Affairs, and chief medical officer at Vertex. “These results demonstrate that inhibition of the APOL1 protein can substantially reduce proteinuria in patients with two APOL1 genetic variants, FSGS and significant proteinuria. We are working with urgency to advance this molecule into pivotal development with the goal of bringing this first-in-class therapy to the more than 100,000 patients in the U.S. and Europe living with APOL1-mediated kidney disease.”

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There were 16 patients in the study. Per the pre-specified statistical analysis plan, three were noncompliant with treatment and were not included in the primary efficacy analysis. Of the 13 that could be evaluated, they received VX-147 with standard of care. They demonstrated a drop in proteinuria from the baseline of -47.6% after receiving the drug for 13 weeks. The data were consistent without regard to the patients’ baseline protein urine levels or background therapy.

There were no serious adverse events. The adverse events seen were mild or moderate, with the most common being headache, back pain and nausea.

“These results are very promising,” said Glenn Chertow, professor of Medicine, Stanford University School of Medicine and chair of the Vertex APOL1 Program Steering Committee. “For decades, I have cared for patients who have suffered from the rapid onset of kidney disease that progresses quickly to kidney failure, which we now know may have been caused by APOL1 gene variants. This approach has tremendous potential, as it targets the underlying genetic driver of kidney disease in these patients. These data demonstrate the potential of VX-147 as a targeted treatment for a patient population at unusually high risk of progression to kidney failure.”

Vertex was recently in the spotlight for its diabetes research after a patient received an infusion of the company’s VX-880, began to produce his own insulin. The patient, Brian Shelton, a former postal delivery carrier forced to retire due to diabetes, was diagnosed with type 1 diabetes more than 40 years ago and was insulin-dependent.

Prior to enrolling in the study, Shelton was on 34 units of insulin per day and had undetectable fasting and stimulated C-peptide levels, meaning he could not produce his own insulin. His glucose-responsive insulin production level was restored 90 days after treatment.


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