Vertex Pharmaceuticals Advances Kidney Disease Drug to Phase 3 Development

Vertex Stock

Vertex Pharmaceuticals (NASDAQ:VRTX) has commenced the late-stage segment of the phase II/III AMPLITUDE study, examining inaxaplin (VX-147) in APOL1-mediated kidney disease (AMKD), a genetic condition impacting kidney function.

This phase III segment aims to assess a 45 mg oral dosage of Vertex’s drug, alongside standard care, in AMKD patients, in comparison to a placebo. Additionally, the study has been extended to include adolescents aged 10 and above with AMKD. Formerly, the AMPLITUDE study exclusively enrolled adults with the condition.

The primary focus of the study for its final analysis is the estimated glomerular filtration rate (eGFR) slope in patients administered inaxaplin versus those given a placebo, with a minimum of two years of data. The eGFR slope acts as an indicator of kidney disease progression.

Vertex intends to conduct a pre-planned interim analysis, evaluating the eGFR slope at week 48. If this interim assessment yields positive results, the management aims to seek FDA approval for the drug through the accelerated pathway.

The AMPLITUDE study is designed to evaluate the impact of inaxaplin on kidney function and proteinuria in individuals affected by proteinuric kidney disease mediated by two variants in the APOL1 gene, known as AMKD.

Year-to-date, Vertex’s shares have seen a 3.3% increase compared to the industry’s 0.4% growth.

Inaxaplin represents a first-in-class, investigative small molecule inhibitor of APOL1, targeting the underlying cause of AMKD. According to management, there are currently no specific therapies for this condition, and the successful development of this drug would address an unmet need within the patient population.

Vertex reaffirmed findings from a phase IIa proof-of-concept (POC) study conducted on inaxaplin in patients with AMKD, which was published in 2021. The results of this study revealed that individuals treated with inaxaplin witnessed an average decrease of 47.6% in the urine protein to creatinine ratio (UPCR) after 13 weeks of treatment in comparison to the baseline levels.

While Vertex maintains a strong position in the cystic fibrosis (CF) market, it has recently achieved success in the development of its non-CF pipeline candidates. Several of these non-CF candidates present multibillion-dollar opportunities.

In December of the previous year, the FDA approved Vertex and partner CRISPR Therapeutics’ (CRSP) Casgevy (exagamglogene autotemcel) for the treatment of sickle cell disease (SCD) in patients aged 12 years and older with recurrent vaso-occlusive crises. Following this approval, Casgevy became the first gene therapy utilizing the Nobel prize-winning CRISPR technology.

In January, Vertex/CRISPR announced that the FDA expanded the label of their one-shot gene therapy Casgevy to include the treatment of transfusion-dependent beta thalassemia (TDT) in patients aged 12 years and older. The CRSP-partnered therapy also obtained approval for both indications this year in various other regions, including Europe, the Kingdom of Saudi Arabia, and Bahrain.

Investors are closely monitoring VX-548, a pain asset. Vertex has concluded three pivotal phase III acute pain studies on this innovative, first-in-class, non-opioid NaV1.8 inhibitor. Results from the studies, disclosed in January 2024, demonstrated that VX-548 treatment significantly reduced pain intensity across various conditions, both surgical and non-surgical, and across different settings. Based on these findings, Vertex plans to submit a new drug application with the FDA for VX-548 for moderate-to-severe acute pain across a broad label by mid-2024.

Last month, the FDA approved Vertex’s investigational new drug application to commence clinical development of its pipeline candidate, VX-407, for the treatment of autosomal dominant polycystic kidney disease (ADPKD). An early-stage study evaluating this drug in healthy volunteers was initiated last month. According to management, ADPKD represents the 10th disease area in Vertex’s clinical pipeline.

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