72-Week Phase 2B ORIGIN Data Highlight Potential Benefit of Atacicept in IgA Nephropathy

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The 72-week open-label extension of the phase 2b ORIGIN trial reveals atacicept's potential as a disease-modifying treatment for IgA nephropathy, showing eGFR stabilization and improvements in key indicators

Richard Lafayette, MD | Credit: Stanford Health Care

Richard Lafayette, MD
Credit: Stanford Health Care

Use of atacicept in patients with IgA nephropathy was associated with eGFR stabilization as well as improvements hematuria, Gd-IgA1, and UPCR over 72 weeks, according to an announcement of results from the open-label portion of Vera Therapeutics’ phase 2b ORIGIN trial.

Coming just more than a month after oral budesonide (Tarpeyo) became the first agent to receive full approval for the management of IgA nephropathy, the announcement of 72-week results from the open-label extension portion of the phase 2b ORIGIN trial help to signify the nephrology community could be sitting at the forefront of a new era in management.1,2

“Data from the OLE show the consistent and sustained reductions of Gd-lgA1, hematuria, and UPCR, as well as the stability of eGFR over 72 weeks in participants with IgAN,” said Richard Lafayette, MD, professor of medicine and director of the Stanford Glomerular Disease Center at Stanford University Medical Center.1 “The demonstration of stable eGFR well beyond a year in participants receiving atacicept represents an important potential advancement for IgAN patients and has potential implications for the future treatment paradigm in this disease.”

According to the announcement from Vera Therapeutics, the company plans to present the new data as part of an internal R&D Day held in New York on January 25, 2024. a global, multicenter, randomized, double-blind, placebo-controlled trial, the ORIGIN trial was launched on the heels of the phase 2 JANUS trial with the intent of assessing the safety and efficacy of atacicept among a cohort of patients with biopsy-proven IgA nephropathy with proteinuria and at high risk of disease progression already on stable RAAS blockade for at least 12 weeks.1,3

The trial enrolled 116 patients and randomized them in a 2:2:1:2 to atacicept 150 mg, atacicept 75 mg, atacicept 25 mg, or matching placebo for a 36-week blinded treatment period. Following completion of the treatment period, patients were offered the option to receive open-label atacicept 150 mg for an additional 60 weeks.1

Of note, 36-week results of the ORIGIN trial were presented at the American Society of Nephrology 2023 Kidney Week and indicated 80% of those receiving atacicept 150 mg experienced hematuria resolution compared to 5% of the placebo group. Further analysis indicated 82% of those using atacicept 150 mg reduced serum Gd-IgA1 to the lowest risk quartile.4

According to the January 25, 2024 announcement from Vera Therapeutics, 106 of the 116 patients who underwent randomization in the phase 2b ORIGIN trial completed the 72-week open-label extension period. In their release, Vera Therapeutics highlighted those treated with atacicept for 72 weeks demonstrated a 62% reduction in Gd-IgA1, a reduction in the percentage of participants with hematuria to 19%, and a 48% reduction in UPCR in the per-protocol analysis.1

Among those who switched from placebo to atacicept, investigators observed similar outcomes across the key indicators of IgAN relative to those who received atacicept during the 36-week blinded treatment period. Specifically, these patients experienced a 59% reduction in Gd-IgA1, a reduction in the percentage of participants with hematuria to 41%, and a 47% reduction in UPCR in the per-protocol analysis.1

“It is also exciting that the data from the OLE show that switching to atacicept halted the eGFR decline seen in participants initially treated with placebo, with similar reductions in Gd-IgA1, hematuria, and UPCR as shown in the active cohort in the first 36 weeks,” Lafayette added.1

The release also called attention to safety results, with safety data indicating the profile observed in OLE period was consistent with the randomized period.1

“We believe these data further support our belief that atacicept has the disruptive potential to stand out as a disease-modifying treatment for patients with IgAN,” said Marshall Fordyce, MD, chief executive officer of Vera Therapeutics.1 “This is an exciting period for Vera as the integrated data package for atacicept continues to mature. Importantly, the ongoing pivotal ORIGIN 3 trial is well underway, with enrollment on track to be completed in the second half of this year.”

The development of atacicept continues into a phase 3 trial named ORIGIN 3. In June 2023, Vera Therapeutics announced the initiation of this trial and, later in the same year, the company presented informational data at Kidney Week 2023 and announced enrollment had begun.4,5

References:

  1. Vera Therapeutics. Vera Therapeutics presents positive 72-week data showing EGFR stabilization in the phase 2B origin clinical trial ole in IGA nephropathy. Vera Therapeutics. January 25, 2024. Accessed January 25, 2024. https://ir.veratx.com/news-releases/news-release-details/vera-therapeutics-presents-positive-72-week-data-showing-egfr.
  2. Brooks A. FDA awards full approval to Budesonide (Tarpeyo) in treatment of IGA nephropathy. HCP Live. December 20, 2023. Accessed January 25, 2024. https://www.hcplive.com/view/fda-awards-full-approval-to-budesonide-tarpeyo-in-treatment-of-iga-nephropathy.
  3. Vera Therapeutics. Vera Therapeutics completes patient enrollment in phase 2b origin clinical trial of ATACICEPT for the treatment of IGA nephropathy. Vera Therapeutics. July 6, 2022. Accessed January 25, 2024. https://ir.veratx.com/news-releases/news-release-details/vera-therapeutics-completes-patient-enrollment-phase-2b-origin.
  4. Vera Therapeutics. Vera Therapeutics presents positive data from phase 2B origin study showing resolution of hematuria in majority of patients at the American Society of Nephrology Kidney Week 2023. Vera Therapeutics. November 4, 2023. Accessed January 25, 2024. https://ir.veratx.com/news-releases/news-release-details/vera-therapeutics-presents-positive-data-phase-2b-origin-study.
  5. Vera Therapeutics. Vera Therapeutics initiates pivotal phase 3 (origin 3) clinical trial of ATACICEPT for the treatment of IGA nephropathy (IgAN). Vera Therapeutics. June 7, 2023. Accessed January 25, 2024. https://ir.veratx.com/news-releases/news-release-details/vera-therapeutics-initiates-pivotal-phase-3-origin-3-clinical.
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