Positive Phase III Results for UCB/Biogen's Dapirolizumab Pegol Offer Hope for Lupus

UCB and Biogen have shared promising topline results from their Phase III PHOENYCS GO trial, which evaluated dapirolizumab pegol, a novel Fc-free anti-CD40L drug candidate, in patients with moderate-to-severe systemic lupus erythematosus (SLE). These encouraging outcomes represent a significant step forward in lupus treatment, an area with substantial unmet medical needs, especially for women.

Systemic lupus erythematosus (SLE) is a chronic autoimmune condition affecting various parts of the body. The disease occurs when the immune system mistakenly attacks the body's own tissues, causing inflammation and potential long-term damage to organs such as the skin, joints, heart, lungs, kidneys, blood cells, and brain. As of 2023, approximately 500,000 people in the United States were living with SLE, with over 90% of cases occurring in women. Among treated SLE patients, around 40% experience relapse or become refractory after their initial therapy.

The primary goals of SLE treatment are to alleviate symptoms, prevent or reduce organ damage and flare-ups, minimize drug toxicity, and improve the patient's quality of life. Standard treatment includes antimalarials like hydroxychloroquine, glucocorticoids such as prednisone, immunosuppressants like methotrexate, azathioprine, or mycophenolate, and biologics. Nonsteroidal anti-inflammatory drugs (NSAIDs) are also used for managing inflammation and pain. Biologics are typically reserved for patients who do not respond to standard treatments or who have severe, organ-threatening disease.

Currently, the biologics approved by the U.S. Food and Drug Administration (FDA) for SLE patients are BENLYSTA and SAPHNELO. BENLYSTA (belimumab) is a fully human monoclonal antibody that targets and inhibits B-lymphocyte stimulator (BLyS), a protein found at elevated levels in patients with autoimmune diseases like SLE. This drug, approved by the FDA in 2011, is notable for being the first approved biologic therapy for active SLE and lupus nephritis in over 50 years. SAPHNELO (anifrolumab) is another fully human monoclonal antibody that targets the type I interferon (IFN) receptor, inhibiting IFN activity. This drug has been approved for SLE treatment in over 60 countries, including the U.S., EU, and Japan.

Emerging treatments in the SLE pipeline include several promising drugs in mid and late stages of development. These include dapirolizumab pegol (UCB/Biogen), litifilimab (Biogen), ianalumab (Novartis), and cenerimod (Idorsia/Viatris), among others. The anticipated launch of these new therapies could significantly impact the market, providing new treatment options and potentially improving patient outcomes.

Dapirolizumab pegol, specifically, is an innovative treatment composed of a humanized, Fc-free antigen-binding fragment conjugated with polyethylene glycol. It works by inhibiting CD40L signaling, which reduces B cell activation, autoantibody production, type 1 interferon secretion, and the activation of T cells and antigen-presenting cells. In September 2024, UCB and Biogen announced the Phase III PHOENYCS GO trial met its primary endpoint, showing clinical improvements in patients with moderate-to-severe SLE. The trial also met key secondary endpoints related to disease activity and flare-ups. Following these positive results, a second Phase III trial named PHOENYCS FLY will be launched in 2024, with long-term monitoring of participants from the PHOENYCS GO study.

Additionally, Biogen is developing litifilimab, an experimental humanized monoclonal antibody targeting blood dendritic cell antigen 2 (BDCA2) on plasmacytoid dendritic cells. This drug inhibits the production of type I interferons and other inflammatory molecules. Litifilimab is currently undergoing Phase III clinical trials to assess its efficacy in treating SLE.

Novartis is working on ianalumab, an antibody targeting the B-cell activating factor receptor (BAFF-R), designed to inhibit BAFF-R signaling and deplete B cells through antibody-dependent cellular cytotoxicity. This drug is also in Phase III trials for SLE, with potential approval expected by 2027.

Cenerimod, another promising treatment, is an oral tablet that selectively modulates the sphingosine-1-phosphate receptor 1 (S1P1). Idorsia Pharmaceuticals has partnered with Viatris to advance and commercialize cenerimod globally, with ongoing efforts to bring this treatment to market.

The introduction of these emerging therapies is expected to transform the SLE treatment landscape, offering new standards of care and driving market growth. According to DelveInsight, the SLE market size is projected to grow from USD 3.2 billion in 2023, with a significant compound annual growth rate anticipated by 2034. This growth is driven by ongoing clinical research and improved diagnostic tools, potentially enhancing the prognosis for SLE patients.