A wave of lupus clinical research advances has been building over the past decade.
Now, it is reaching a crest.
A 2025 pipeline report identifies over 140 lupus therapies from 120+ companies now in clinical trials.i This surge of innovation is translating into potential treatments that are targeted, safer, and showing potential effectiveness for people living with lupus—offering more choices and options for treating the disease.
“This is a time like no other in lupus clinical research,” said Stacie J. Bell, PhD, Chief Clinical Research Officer, Lupus Therapeutics. “There are not only more clinical trials, but also more reaching Phase 3—the final step before regulatory approval.”
Lupus Therapeutics, the clinical affiliate of the Lupus Research Alliance, oversees the Lupus Clinical Investigators Network (LuCIN). The network consists of 60+ leading medical research institutions in North America that collaborate on 25-30% of lupus clinical trials and reach more than 160,000 patients. LuCIN and Lupus Therapeutics enhance studies through clinical operations and science expertise, advisory services, patient engagement, and partnership with biopharmaceutical companies and research institutions.
“The moment we are in was decades in the making,” said Dr. Richard Furie, Chief of the Division of Rheumatology at Northwell and the recent recipient of the Lupus Therapeutics Impact Award in Lupus Clinical Trials Investigation. “This is a moment of unprecedented progress, where every trial, data point, and discovery are getting us closer to new treatments that further improve the lives of people living with lupus.”
What Is New in Lupus Treatment Development?
Clinical researchers are evaluating a range of lupus treatments with the aim of modulating, and in some cases, resetting the immune system.
“While engineered cell therapies represent an exciting new treatment paradigm, they are only part of the story,” said Dr. Bell. “We are seeing several strategies to target harmful B cells, and oral therapies that target inflammatory pathways. All of these mark a bold shift—from decades of symptom management to changing the course of lupus as a disease.”
This shift took center stage at ACR Convergence 2025, where leading lupus experts shared the latest findings.
The Lupus Cascade
In lupus, the immune system, meant to defend against infections, produces autoantibodies that mistake the body’s own cells as foreign, causing other immune cells to attack organs such as the kidneys, brain, heart, lungs and skin, as well as blood and joints. Overactive B cells produce autoantibodies that, along with T cells, damage healthy tissues and accumulate in organs. Adding to this process, immune-signaling proteins called cytokines are overproduced, leading to more inflammation. Meanwhile, the body’s natural controls fail, allowing these B and T cells to continue their assault unchecked.
The last 60 years of lupus treatment, despite a few approvals, have relied primarily on broad-acting drugs that suppress the entire immune system, addressing overall inflammation but often causing significant side effects. Researchers are now focused on therapies designed to be more precise, targeting and disrupting the lupus cascade at specific points.
These treatments aim to modulate specific inflammatory signals, precisely target the problematic B cells, or even intensely modify or reset the entire immune system for long-term remission. Here are the waves to watch:
Modulating the Immune System in More Targeted Ways
What’s New: New oral drugs in the pipeline are targeting specific inflammatory pathways to achieve new approaches to decrease inflammation to augment current treatments and provide further options.
Why It’s Exciting: Many commonly used oral immunosuppressants suppress the entire immune system, leaving patients vulnerable to infection and causing significant side effects. Newer oral therapies target specific overactive inflammation pathways. They include small molecule drugs that block the TYK2 enzyme, which relays inflammatory signals, and monoclonal antibodies that block the type 1 interferon pathway, a key driver of inflammation in lupus.
Targeting B Cells More Effectively
What’s New: While B-cell targeting has been a focus for some time, there is new data on potentially more effective B-cell therapies. They include monoclonal antibodies and bispecific antibodies (that combine two targeting mechanisms in one therapy), as well as small molecule drugs that disrupt B-cell signaling. These treatments are designed to offer more specific or longer-lasting B-cell depletion.
Why It’s Exciting: By selectively targeting B cells and their key survival signals, these innovative therapies offer a more precise alternative to older, broad-acting immunosuppressants. Notably, the FDA recently approved obinutuzumab for lupus nephritis. This next-generation monoclonal antibody more effectively depletes B cells—aiming to prevent or delay progression to end-stage kidney disease, often resulting in dialysis or transplantation.
Resetting—or Modulating—the Immune System
What’s New: The most transformative developments are coming from cell-based therapies that aim to reset the immune system for potential long-term, drug-free remission. These include autologous and allogenic CAR T-cell therapy. In the first, a patient’s T cells are collected, genetically engineered to destroy bad B cells, and reinfused into the patient. In the second, donor cells are modified and infused into patients. The latter offers an off-the-shelf, potentially less expensive alternative that can be produced at scale. In addition, there are other approaches being taken with natural killer (NK) cells, stem cells, in vivo CAR T (the body produces T cells that attack the B cells). Most recently, T cell engagers have generated excitement. Bi-specific T-cell engagers (BiTE) is a class of bispecific monoclonal antibodies that interact with T cells and direct them to target B cells resulting in deep B cell depletion. Preliminary data are promising, but further investigation is required.
Why It’s Exciting: This category represents a fundamental shift from managing symptoms to potentially inducing long term remission or even a cure of the underlying disease. Data from early-phase trials has shown remarkable success in severely ill patients, with remission reported in some cases.
Where We Are Headed
With LuCIN and Lupus Therapeutics helping to drive the evaluation of emerging treatment strategies, Dr. Bell has a unique vantage point on where the field is headed. “The progress being made in lupus clinical research is very exciting and I have reason to be hopeful that there are many new treatment options on the horizon.”
For the millions of people worldwide living with lupus, these advancements offer more than a swell of hope—they bring the prospect of fuller, healthier lives within closer reach.
i AB Newswire. Systemic lupus erythematosus pipeline heats up as 120 companies advance cutting-edge therapies/DelveInsight. ABNewswire. https://www.abnewswire.com/pressreleases/systemic-lupus-erythematosus-pipeline-heats-up-as-120-companies-advance-cuttingedge-therapies-delveinsight_748163.html. Accessed September 22, 2025.
