15 Sep BIOGEN: Trial of Anti-BDCA2 Antibody Litifilimab for Systemic Lupus Erythematosus
MedicalResearch.com Interview with:
Nathalie Franchimont, M.D., Ph.D.
Senior Vice President, Head of Multiple Sclerosis and Immunology
Head of the Multiple Sclerosis and Immunology Development Unit
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organ systems. Rash and arthritis are among the most frequent manifestations of the disease and severe organ damage can also occur especially when organs like the kidney are affected. Litifilimab (known as BIIB059) is a monoclonal antibody being studied for the potential treatment of SLE and cutaneous lupus erythematosus (CLE).
The Phase 2 LILAC study evaluated litifilimab versus placebo in two parts: Part A in participants who have SLE with active joint and skin manifestations; and Part B in participants with active CLE, including chronic and subacute subtypes, with or without other organ involvement. Results from the SLE portion of the study (Part A) show litifilimab met the study’s primary endpoint by significantly reducing total active joint count compared to placebo. Total active joint count was defined as the total number of tender or swollen joints. Litifilimab was generally well tolerated, with most reported adverse events (AEs) rated as mild or moderate. Note, this Phase 2 trial was not powered to assess secondary endpoints.
Based on these positive Phase 2 results, Biogen is currently enrolling participants into the Phase 3 TOPAZ-1 and TOPAZ-2 studies, which will evaluate the efficacy and safety of litifilimab in participants with active SLE worldwide.
Part B results from LILAC were published separately in NEJM on July 28, 2022 and expand the body of evidence supporting litifilimab as a potential first-in-class therapy for cutaneous lupus erythematosus in addition to SLE.
MedicalResearch.com: What should readers take away from your report?
Response: Litifilimab, discovered and developed in-house by Biogen scientists, is a humanized IgG1 monoclonal antibody (mAb) targeting blood dendritic cell antigen 2 (BDCA2) and is being investigated for the potential treatment of SLE and CLE. Litifilimab targets a receptor that is predominately expressed on a subset of immune cells, called plasmacytoid dendritic cells (pDCs), that are found at the site of inflammation in key organs affected by lupus including the joints and skin. In SLE, results from LILAC showed via an organ specific approach that litifilimab administration was associated with a decrease in total active joint counts.
We are pleased that the NEJM has published the totality of data from the LILAC program which reinforces our belief in the potential of litifilimab as a first-in-class therapy for both systemic and cutaneous lupus. The encouraging results from the Phase 2 LILAC study provide support for us to further characterize the safety and efficacy of litifilimab in longer and larger studies in both SLE and CLE. To. Biogen is currently enrolling participants into the Phase 3 TOPAZ-1 (NCT04895241) and TOPAZ-2 (NCT04961567) studies, which will evaluate the efficacy and safety of litifilimab in participants with active SLE at 269 clinical trial sites worldwide. We are initiating a pivotal study of litifilimab in CLE in 2022 (NCT05531565).
Lupus is a chronic autoimmune disease that disproportionately affects women and people of color who have historically been underserved in medicine and face greater challenges accessing care. There is currently no cure. Lupus can cause debilitating symptoms and irreversible skin and organ damage which, if left untreated, can have a lasting negative impact on functional and psychological aspects of people’s lives. Despite advancements over the past two decades in treating autoimmune indications, both SLE and CLE represent a high unmet medical need.
MedicalResearch.com: What recommendations do you have for future research as a results of this study?
Response: Lupus is a complex disease affecting multiple system/organs. In recent years, a growing body of evidence from lupus clinical research has shown that there are multiple clinical phenotypes /endotypes, for whom symptoms development may involve different cellular pathways in the innate and/or adaptive immune system. As a consequence, not all patients may respond to one specific drug. To help people living with lupus and treating physicians get the appropriate treatment to rapidly control the disease activity and avoid damage, it is important to further understand what parameters (clinical, genetic biomarkers, etc.) are associated with a response to treatment. In addition, further mechanistic investigation is needed to better understand the role of pDCs in lupus.
MedicalResearch.com: Is there anything else you would like to add? Any disclosures?
Response: At Biogen, our goal is to discover and develop new treatment options that not only reduce lupus disease activity but also decrease clinical manifestations that impact patients the most. Decades of study on pathways at the intersection of neurology and immunology have provided Biogen with expertise in specialized immunology. We are currently advancing two lupus therapies – litifilimab and dapirolizumab pegol (being developed in collaboration with UCB) – in Phase 3 trials.
We look forward to continuing our evaluation of litifilimab in Phase 3 studies and sharing additional data when available.
Disclosure: I am an employee at Biogen.
T rial of Anti-BDCA2 Antibody Litifilimab for Systemic Lupus Erythematosus
Richard A. Furie, M.D., Ronald F. van Vollenhoven, M.D., Kenneth Kalunian, M.D.,
Sandra Navarra, M.D., Juanita Romero-Diaz, M.D., Victoria P. Werth, M.D.,
Xiaobi Huang, Ph.D., George Clark, B.S., Hua Carroll, M.D.,
Adam Meyers, M.S., Cristina Musselli, M.D.,
Catherine Barbey, Ph.D., et al., for the LILAC Trial Investigators*
September 8, 2022
N Engl J Med 2022; 387:894-904
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