Aurinia Launches PRESERVE Phase 4 Trial: LUPKYNIS Combined with Biologics to Pursue Faster Complete Renal Response in Lupus Nephritis
核心洞察
Aurinia Pharmaceuticals has initiated PRESERVE, a Phase 4 multicenter study combining LUPKYNIS (voclosporin) with belimumab, obinutuzumab, or anifrolumab in lupus nephritis (搜索) patients.
The trial plans to enroll approximately 150 patients across roughly 50 U.S. sites, with the primary endpoint being the proportion of patients achieving complete renal response at 6 months.
Investigators highlight a multitarget therapeutic approach targeting non-redundant biological pathways—T cells, B cells, and type 1 interferon signaling—to potentially halt nephron damage more rapidly.
ROCKVILLE, Md. & EDMONTON, Alberta — Aurinia Pharmaceuticals Inc. (NASDAQ: AUPH) announced on July 6, 2026, the initiation of PRESERVE, a Phase 4, multicenter clinical study designed to evaluate LUPKYNIS (voclosporin) in combination with three distinct biologic agents — belimumab, obinutuzumab, or anifrolumab — in patients with lupus nephritis (搜索). The trial, now actively recruiting, represents a strategic effort to determine whether multitarget combination therapy can deliver a faster and more robust kidney response than current approaches.
The study plans to enroll approximately 150 patients across approximately 50 sites in the United States. Its primary endpoint is the proportion of patients achieving complete renal response (CRR) at 6 months, a measure that has proven difficult to attain for the majority of patients even with recently approved therapies.
A Multitarget Strategy Grounded in Distinct Mechanisms
PRESERVE builds on the established efficacy of LUPKYNIS, the only FDA-approved oral therapy for lupus nephritis (搜索) and the only treatment for the condition that has demonstrated a statistically significant increase in CRR after 6 months of therapy. The trial pairs voclosporin — a calcineurin inhibitor that protects the kidneys by directly stabilizing podocytes and inhibiting T cell activation — with biologics that intervene at different nodes of the immune cascade.
Belimumab, a B cell-activating factor (BAFF (搜索)) inhibitor, is indicated for both systemic lupus erythematosus (SLE) and lupus nephritis (搜索). Obinutuzumab, a CD20 (搜索)-directed cytolytic antibody, is also indicated for lupus nephritis. Anifrolumab, a type 1 interferon receptor (搜索) antagonist, is indicated for SLE. All three are combined with standard-of-care agents including mycophenolic acid analogs and corticosteroids.
“There is great mechanistic rationale in combining LUPKYNIS with these biologic agents to improve outcomes,” said Arvind Madan, MD, Physician and Principal Investigator of the Research Division at Central Florida Kidney Specialists and Co-Lead Investigator of PRESERVE. “LUPKYNIS protects the kidneys by directly stabilizing podocytes and inhibiting T cell activation, belimumab and obinutuzumab inhibit B cell activation, and anifrolumab blocks type 1 interferon signaling. By taking a multitarget therapeutic approach that intervenes in non-redundant biological pathways, each of which independently contribute to nephron loss, there is the potential to stop nephron damage more rapidly in the short term and preserve more kidney function in the long term.”
Addressing a Persistent Unmet Need
Despite recent therapeutic advances, achieving timely and complete renal response remains a significant clinical challenge. Anca Askanase, MD, MPH, Chair of the Department of Medicine and Chief of the Division of Rheumatology at Hospital for Special Surgery and Co-Lead Investigator of PRESERVE, underscored the urgency: “As underscored by the recently published American College of Rheumatology guidelines for the treatment of lupus nephritis (搜索), the goal of treatment should be to arrest proteinuria, which is the hallmark sign of ongoing kidney damage, as quickly as possible. Unfortunately, even with the newer agents approved in the past few years, the majority of patients do not achieve CRR by 6 months, and many do not achieve CRR even by 12 months.”
Study Design and Current Status
PRESERVE employs a single-arm design in which all enrolled patients receive the combination approach. There is no blinding, meaning both physicians and patients are aware of the treatments being administered. This real-world-style design prioritizes the collection of kidney response and safety data in a setting that mirrors clinical practice.
The trial was first submitted on May 13, 2026, and the latest update on June 11, 2026, confirmed active recruitment. Further details and ongoing updates are available on ClinicalTrials.gov.
Broader Implications for the Lupus Nephritis (搜索) Landscape
Positive data from PRESERVE could support broader utilization of LUPKYNIS and strengthen its competitive positioning against other lupus nephritis (搜索) treatment options. The study also involves drugs from larger pharmaceutical companies, including GSK (belimumab) and AstraZeneca (anifrolumab), meaning any signals of synergy or safety concerns could influence sentiment across the entire lupus nephritis treatment space.
Aurinia is also advancing aritinercept, a dual inhibitor of BAFF (搜索) and a proliferation-inducing ligand (APRIL), for the potential treatment of autoimmune diseases, further expanding its pipeline in immunology.