Inaxaplin Cuts Proteinuria in Broader APOL1 Kidney Disease Population

Published on: September 23, 2026

Phase 2b AMPLIFIED data show a 42.7% UACR drop in AMKD with modest proteinuria; AMPLITUDE interim data are due early 2027.

Inaxaplin reduced urine albumin to creatinine ratio (UACR) by 42.7% at Week 13 in people with APOL1-mediated kidney disease (AMKD) and modest proteinuria, according to topline results from the Phase 2b AMPLIFIED study.¹ A smaller reduction of 17.3% was seen in a second cohort of people with AMKD and type 2 diabetes.

There are currently no approved therapies for AMKD, which affects about 150,000 people in the US and Europe.¹ Both AMPLIFIED populations fall outside the scope of the pivotal Phase 2/3 AMPLITUDE trial, which Vertex Pharmaceuticals said has completed enrollment and remains on track for interim results in early 2027. If positive, those results could support accelerated approval in the US.

APOL1 Kidney Disease: Where the Field Stands

In more than 15 years since APOL1 was linked to kidney disease, it has become one of the strongest known genetic risk factors in nephrology. Clinicians still face gaps in diagnosis, risk prediction, and access to testing. Experts from Mount Sinai, the University of Pennsylvania, and the American Kidney Fund discuss hypertensive nephrosclerosis misclassification, a new proteomic risk score, and why inaxaplin represents "a true example of precision medicine in nephrology."³

Read the feature: APOL1-Mediated Kidney Disease: From Genetic Discovery to the Edge of Precision Medicine

"These results add to the evidence base for inaxaplin and its potential as a first- and best-in-class treatment targeting the underlying cause of AMKD," Carmen Bozic, MD, executive vice president, global medicines development and medical affairs, and chief medical officer at Vertex, said in a statement.¹

AMPLIFIED Trial Design: Inaxaplin Beyond Severe Proteinuria

AMPLIFIED was a Phase 2, single-arm, open-label study. It evaluated inaxaplin 45 mg once daily for 13 weeks on top of optimized standard of care.¹ The primary endpoint was mean percent change in UACR from baseline to Week 13, assessed separately for each cohort. Other endpoints were change in urine protein to creatinine ratio (UPCR) and safety.

The study enrolled and dosed 41 people in 2 cohorts:

Cohort 1 (n = 23): AMKD with modest proteinuria, defined as UACR ≥0.1 g/g to <0.42 g/g
Cohort 2 (n = 18): AMKD with type 2 diabetes and UACR ≥0.1 g/g to <6 g/g

Per the prespecified analysis plan, 2 people who were noncompliant with treatment were excluded from the efficacy analyses, 1 from each cohort. Week 13 analyses included 18 people in cohort 1 and 14 in cohort 2.¹

Inaxaplin Reduces UACR 42.7% in AMKD With Modest Proteinuria

In cohort 1, mean baseline UACR was 0.28 g/g. At Week 13, UACR fell by 42.7% (95% Confidence Interval [CI], −58.3% to −21.1%) and UPCR fell by 44.7% (95% CI, −60.9% to −21.9%).¹ All confidence intervals were generated post hoc.

According to Vertex, these reductions are consistent with the Phase 2a study of inaxaplin in AMKD with focal segmental glomerulosclerosis (FSGS). That study reported a 43.4% reduction in UACR and a 47.6% reduction in UPCR at Week 13.¹,² Most people in the AMPLIFIED modest proteinuria cohort did not have an FSGS diagnosis.

"These patients were already well treated with foundational chronic kidney disease therapies and treatment with inaxaplin led to additional reductions in proteinuria," Glenn Chertow, MD, MPH, professor of medicine at Stanford University School of Medicine and chair of the Vertex APOL1 Program Steering Committee, said in a statement.¹

Smaller UACR Reduction in AMKD With Type 2 Diabetes

Cohort 2 had a greater mean baseline UACR, at 0.67 g/g. At Week 13, UACR fell by 17.3% (95% CI, −36.3% to 7.2%) and UPCR fell by 25.4% (95% CI, −45.1% to 1.4%).¹

"We are also excited with the treatment effect, though smaller in magnitude, in the type 2 diabetes cohort," Bozic said. "We look forward to discussing the AMPLIFIED results with regulators in the context of the AMPLITUDE pivotal study."

Inaxaplin Safety Profile in the AMPLIFIED Study

Inaxaplin was generally well tolerated in both cohorts. No serious adverse events (AEs) were related to treatment, and all AEs were mild or moderate.¹

Headache was the most common AE, occurring in 7.3% of participants. In total, 5 participants had isolated, asymptomatic transaminase elevations, all of which resolved.

AMPLITUDE Interim Analysis and Path to Accelerated Approval

AMPLITUDE is a global Phase 2/3 trial comparing inaxaplin 45 mg once daily with placebo, both on top of standard of care, in people with AMKD and severe proteinuria who have no other kidney disease-causing comorbidities.¹ The primary endpoint for the final analysis is eGFR slope after 2 years of treatment.

The interim analysis will take place once the interim cohort reaches 48 weeks of treatment.¹

"I am looking forward to the AMPLITUDE interim analysis and am hopeful that we'll soon have a potentially disease-specific and disease-modifying therapy to offer to patients living with AMKD," Chertow said.

References

Vertex Pharmaceuticals Incorporated. Vertex announces positive results from Phase 2b AMPLIFIED study of inaxaplin in additional populations of people with APOL1-mediated kidney disease (AMKD) and completion of enrollment in the Phase 2/3 AMPLITUDE trial. Press release. September 22, 2026. Accessed September 23, 2026. https://news.vrtx.com/news-releases/news-release-details/vertex-announces-positive-results-phase-2b-amplified-study
Egbuna O, Zimmerman B, Manos G, et al. Inaxaplin for proteinuric kidney disease in persons with two APOL1 variants. N Engl J Med. 2023;388(11):969-979. doi:10.1056/NEJMoa2202396
Meliambro K, Campbell K, Garimella P, et al. APOL1-mediated kidney disease: from genetic discovery to the edge of precision medicine. HCPLive. Accessed September 23, 2026. https://www.hcplive.com/view/apol1-mediated-kidney-disease-from-genetic-discovery-to-the-edge-of-precision-medicine