UCB and Biogen announce positive Phase 3 results for dapirolizumab pegol in systemic lupus erythematosus

Belgian biopharma UCB and U.S. biotech Biogen today announced positive results from a Phase 3 study testing their drug candidate dapirolizumab pegol in people with systemic lupus erythematosus (SLE). The primary endpoint was met, revealing a significant clinical improvement in moderate-to-severe SLE. The two companies have decided to advance dapirolizumab pegol in a second Phase 3 study in 2024.

SLE is the systemic form of lupus, a chronic autoimmune disease that affects different organs and is characterized by periods of flare-ups alternating with periods of inactivity. Symptoms include rashes, arthritis, anemia, thrombocytopenia (low platelet count in the blood), inflamed kidneys, psychosis, and seizures. 90% of affected people are women. Pregnancies in women with SLE are seen as high risk, with increased risk of mortality and morbidity for both the mother and fetus.

As SLE flare-ups are unpredictable and many different organs are involved, the treatment of SLE patients remains challenging for clinicians. Current therapies include​ glucocorticosteroids and biologics, such as GSK’s monoclonal antibody belimumab (Benlysta) and AstraZeneca’s monoclonal antibody anifrolumab (Saphnelo). However, while glucocorticosteroids can effectively and quickly suppress inflammatory flares, they can cause severe side effects, including organ damage.

Overall, there is still a high unmet need for new treatment options. To this end, UCB and Biogen’s dapirolizumab pegol takes a different approach to those biologics already on the market, which are monoclonal antibodies. Dapirolizumab pegol, on the other hand, is a humanized, Fc-free polyethylene glycol-conjugated antigen-binding fragment. This means it is not an entire antibody, but rather an antibody fragment that is smaller in size and can more easily access difficult-to-reach targets on cells and tissues.

In SLE and other autoimmune diseases, B cells are known to boost autoimmunity and produce autoantibodies that drive inflammation. Dapirolizumab pegol works by blocking a specific signaling pathway called CD40L and, as a result, reduces B cell activation and the production of autoantibodies. At the same time, other inflammatory pathways are also inhibited.

“Our hypothesis is that impacting the CD40L pathway, a central mechanism in immune response, would translate to significant impact on SLE disease burden,” said Diana Gallagher, Head of AD, MS and Immunology Development Units at Biogen, in a press release.

“[Our] results demonstrate that dapirolizumab pegol has the promise to provide meaningful benefit in this serious, chronic, and often devastating disease. We are committed to delivering new treatment options for this autoimmune disease and believe the overall efficacy and safety seen in PHOENYCS GO support further development of dapirolizumab pegol in SLE.”

PHOENYCS GO is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study where participants either received dapirolizumab pegol in combination with standard-of-care or a placebo with standard-of-care. After week 48, patients receiving dapirolizumab pegol as an add-on therapy to standard-of-care showed improvements in moderate-to-severe disease activity. Clinical improvements were also seen in secondary endpoints, assessing disease activity and flares.

“These positive results with dapirolizumab pegol represent encouraging progress in the development of medicines that can improve the lives of those living with lupus, an area that remains one of high unmet medical need and where women are disproportionately affected,” said Fiona du Monceau, Head of Patient Evidence at UCB, in a press statement.

"[...] As we pursue the next steps in the clinical development of this potentially differentiated treatment, we extend our appreciation to the patients, study investigators, and the clinical community for their ongoing support and participation in this important research.”