Inaxaplin Shows Promise for APOL1-Mediated FSGS in Phase 2a Trial


A phase 2a trial of provides data detailing the effects of inaxaplin, a small molecule APOL1 inhibitor, on urinary protein-to-creatinine ratio in people with focal segmental glomerulosclerosis and two APOL1 variants.

Glenn Chertow, MD, MPH | Courtesy: Stanford Healthcare

Glenn Chertow, MD, MPH
Courtesy: Stanford Healthcare

Data from a phase 2a trial examining use of inaxaplin suggests the small-molecule APOL1 inhibitor could prove useful as a treatment in people with focal segmental glomerulosclerosis (FSGS) and two APOL1 variants.

A disease with a high degree of unmet need, results of the trial, which included 13 participants who were treated with inaxaplin suggest use of the agent was associated with a 47.6% reduction in urinary protein-to-creatinine ratio (UPCR) at week 13, with no adverse events leading to discontinuation.1

“The results from the phase 2 inaxaplin study show real promise for patients suffering from [APOL1-mediated kidney disease],” said Glenn Chertow, MD, MPH, Professor of Medicine, Stanford University School of Medicine and Chair of Vertex’s APOL1 Program Steering Committee.2 APOL1-mediated kidney disease can progress swiftly to kidney failure, and the potential for inaxaplin to precisely target the underlying cause of [APOL1-mediated kidney disease] should bring hope and excitement to persons living with [APOL1-mediated kidney disease] and those of us who care for them.”

A single arm, open-label, 2-part study sponsored by Vertex Pharmaceuticals, the current study was launched with the intent of examining the efficacy, safety and pharmacokinetics of inaxaplin in patients with APOL1-mediated kidney disease with FSGS based on the results of previous studies. With this in mind, investigators recruited a cohort of 16 individuals with two APOL1 variants, biopsy-proven FSGS, proteinuria, and an eGFR 27 mL/min/1.73m2 or greater. Per trial protocol patients received inaxaplin daily for 13 weeks along with standard care. Investigators noted participants received 15 mg inaxaplin for 2 perks and 45 mg for the final 11 weeks.1

The primary outcome of interest for the trial was the percent change form baseline in UPCR at week 13 among participants who had at least 80% adherence to inaxaplin therapy. Secondary outcomes of interest for the trial included safety and pharmacokinetics. Investigators pointed out the safety analysis was based on adverse events, clinical laboratory values, standard 12-lead ECG, and vital signs.1

Of the 16 participants who underwent enrollment, a cohort of 13 participants were treated and met the trial’s adherence threshold. Among this group, the mean change from baseline to week 13 in UPCR was -47.6% (95% CI, -60.0 to -31.3). Further analysis, which included all patients regardless of adherence threshold, suggested all participant experienced similar reductions, with a mean change of -44.0% (95% CI, -56.3 to -28.3) and only a single participant not experiencing a reduction.1

Safety analyses indicated 94% of the participants included in the trial experienced an adverse event, but all adverse events were considered mild or moderate, with no treatment discontinuations observed in the trial as a result of adverse events. Investigators noted the oily adverse events occurring in more than 2 participants were headache, back pain, and nausea.1

In an editorial, Neil R. Powe, MD, of the Univeristy of California San Francisco, expressed cautious optimism surrounding the results of the study, citing limitations in the trial design, and considered the trial to be a step forward for precision medicine in nephrology.3

“The results of these investigations by Egbuna et al. constitute a step forward in making the promise of precision medicine a reality by means of industry–academia collaboration and the targeting of the large excess risk of end-stage kidney failure among Black persons in the United States for which the two prevalent APOL1 risk variants (occurring in one in eight Black adults) contribute to health inequity,” Powe wrote.3

In their release, Vertex Pharmaceuticals highlighted their ongoing clinical trial program examining the utility of inaxaplin in APOL1-mediated kidney disease.

“Inaxaplin has the potential to be a breakthrough for people living with AMKD by addressing the underlying cause of this devastating disease,” said Carmen Bozic, MD, Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex.2 “We look forward to exploring the full potential of this molecule in the ongoing Phase 2/3 pivotal trial and bringing this potential therapy to patients who are waiting.”


  1. Egbuna O, Zimmerman B, Manos G, et al. Inaxaplin for proteinuric kidney disease in persons with two apol1 variants. New England Journal of Medicine. 2023;388(11):969-979. doi:10.1056/nejmoa2202396
  2. Vertex announces publication in New England Journal of Medicine of results from phase 2 study of Inaxaplin (VX-147). Vertex Pharmaceuticals Newsroom. Published March 16, 2023. Accessed March 16, 2023.
  3. Powe NR. A step forward for precision equity in kidney disease. New England Journal of Medicine. 2023;388(11):1043-1044. doi:10.1056/nejme2301003
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