Treatments being studied for lupus

Many drugs, both old and new, are now being studied in people with lupus. The drugs described below are not a complete list of all the drugs currently in development for lupus, and they may not all end up as approved medications. However, the variety of scientific approaches reflects the growing interest in lupus at all levels of the biomedical and pharmaceutical industry.

Much has been learned about trial designs for lupus studies. There is continued interest in lupus by many biomedical and pharmaceutical companies worldwide, offering realistic hope that we will see additional treatments for lupus in the not-too-distant future.

Phase III Trials

In Phase III clinical trials, researchers evaluate a new drug's effectiveness in a large, diverse group—usually over 100 participants—under real-world conditions. These trials compare the investigational drug to existing treatments, explore different doses and combinations, and confirm safety and efficacy before regulatory approval.

Upadacitinib (Rinvoq®) is an FDA-approved JAK inhibitor for moderate to severe rheumatoid arthritis and active psoriatic arthritis. It targets immune enzymes to reduce inflammation and immune overactivity, with ongoing research assessing its potential for lupus treatment.

Deucravacitinib (SOTYKTU™) is a Tyk2 inhibitor currently approved for moderate-to-severe plaque psoriasis. This drug works by preventing cytokine production, limiting immune cell activation and survival. Ongoing studies aim to determine its effectiveness in managing lupus symptoms.

Cenerimod is a treatment that targets a protein called sphingosine 1-phosphate receptor 1 (S1P1), which helps control the movement of immune cells in the body. By blocking S1P1, Cenerimod reduces the flow of T and B cells (immune cells) into the bloodstream, potentially helping to calm the immune system and reduce lupus symptoms.

Anifrolumab (Saphnelo®) is a monoclonal antibody approved by the FDA for treating systemic lupus erythematosus (SLE). It is currently being studied for lupus nephritis. Anifrolumab works by blocking Type I interferons from attaching to their receptors, which helps reduce immune system overactivity associated with lupus.

Litifilimab is a monoclonal antibody that works by targeting BDCA2, a protein on plasmacytoid dendritic cells, to prevent the production of interferons, which are involved in the inflammation and immune overactivity seen in lupus. This may help reduce lupus symptoms by lowering excessive immune responses. It is currently being studied for both cutaneous and systemic lupus erythematosus (SLE).

Obinutuzumab (Gazyva®) is a treatment that works by blocking the activation of B cells, which contribute to lupus symptoms. Positive results from studies show significant improvements in kidney function and other markers of lupus after 104 weeks. Obinutuzumab is already approved for certain types of leukemia and lymphoma and is likely to be approved for lupus treatment soon. There also are ongoing studies in patients with lupus nephritis as well.

Ianalumab is a monoclonal antibody that works by targeting and eliminating certain B cells that are involved in the immune system's overactivity in lupus. This approach is designed to reduce the harmful effects of these immune cells, which contribute to inflammation and damage in lupus. It is currently being studied to treat lupus nephritis and systemic lupus erythematosus (SLE).

Telitacicept (Tai'ai®) is a TACI-Fc fusion protein that has been conditionally approved in China for systemic lupus erythematosus (SLE)and may also be considered for rheumatoid arthritis (RA). This biologic works by preventing the activation of B cells, which play a key role in the immune system’s overreaction in lupus. In Phase II trials, all treatment endpoints were met, showing promising results for those with lupus.

Emapalumab (Gamifant®) is a monoclonal antibody that is currently being studied for use in systemic lupus erythematosus (SLE). It is the first FDA-approved treatment for primary hemophagocytic lymphohistiocytosis (HLH), a rare condition characterized by severe inflammation. Emapalumab works by targeting and neutralizing interferon gamma (IFNγ), a protein involved in causing inflammation. Though originally developed for HLH, research is ongoing to assess its potential in treating SLE, where excessive inflammation plays a key role in disease activity.

Dapirolizumab pegol is a monoclonal antibody that works by targeting and binding to CD40 ligand (CD40L), a protein that plays a crucial role in immune system activation. By blocking CD40L, dapirolizumab pegol helps reduce the activation of B cells, which are involved in producing autoantibodies that attack the body’s own tissues. It also limits the production of type 1 interferon (IFN), a protein that contributes to inflammation in lupus. This approach aims to decrease disease activity and improve symptoms in lupus patients.