Vertex Pushes Oral Drug into Phase III Kidney Disease Trial, Eyes Accelerated Approval

Vertex Pharma_iStock, hapabapa

Pictured: Vertex Pharmaceuticals’ office in Boston, Massachusetts/iStock, hapabapa

Vertex Pharmaceuticals on Monday announced that it has advanced its drug candidate inaxaplin into the Phase III portion of the pivotal AMPLITUDE clinical trial, assessing the investigational oral medicine in APOL-1 mediated kidney disease.

The trial will evaluate the effects of a 45-mg once-daily dose of inaxaplin versus placebo on organ function and proteinuria in patients with APOL-1 mediated kidney disease (AKMD). Patients, which include adults and adolescents aged 10 to 17 years, will also receive standard of care on top of the study treatment.

AMPLITUDE is designed with a pre-planned interim analysis of estimated glomerular filtration rate (eGFR) as a measure of kidney function at 48 weeks. If positive, findings from the analysis could push Vertex to seek accelerated approval of inaxaplin in this indication.

CMO Carmen Bozic in a statement called inaxaplin a “first-in-class molecule that addresses the underlying cause” of AKMD. “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.”

Monday’s announcement comes after inaxaplin cleared the Phase IIa proof-of-concept phase of AMPLITUDE. In March 2023, Vertex announced that it had published these data in The New England Journal of Medicine, demonstrating that inaxaplin treatment led to a 47.6% reduction in proteinuria at 13 weeks, an effect that was “statistically significant and clinically meaningful.”

The Phase II data also showed that inaxaplin’s effects arose early in the study and persisted throughout 13 weeks of treatment. In terms of safety, inaxaplin was overall well-tolerated. Its most common side effects were headache, back pain and nausea.

According to Vertex, these Phase II data represent the “first clinical evidence” showing that a small molecule oral drug targeting APOL1 could reduce proteinuria in AKMD patients.

Afflicting around 100,000 patients in the U.S. and Europe, AKMD is a specific type of chronic kidney disease caused by genetic variants in the APOL1 gene, which encodes a protein that forms part of high-density lipoprotein cholesterol. Mutations to APOL1 could give rise to cell injury and death in the kidneys, which in turn could manifest as protein in the urine, poor kidney function, the need for transplant and ultimately death.

Inaxaplin targets the underlying cause of AKMD by blocking APOL1. In June 2022, the drug candidate secured the FDA’s Breakthrough Therapy designation, which paved the way for an expedited review process.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at or

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