Biogen, Inc. and UCB S.A.‘s decision to persevere with dapirolizumab pegol in systemic lupus erythematosus (SLE) despite a mid-stage failure six years ago appears to have paid off with the firms heralding a Phase III success for the anti-CD40L antibody.
The long-time partners have announced positive topline results from the Phase III PHOENYCS GO study which demonstrate that dapirolizumab pegol, in addition to standard-of-care, met the primary endpoint on the British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) scale of greater improvement of moderate-to-severe disease activity after 48 weeks versus placebo in addition to SOC. Improvements were observed among key secondary endpoints including flares and the safety profile was generally consistent with previous studies and with that expected in participants with SLE receiving an immunomodulator.
UCB and Biogen provided no specific data from the 321-subject trial but noted that they were initiating a second Phase III study called PHOENICS FLY which would continue to follow participants from PHOENYCS GO in a long-term open-label trial. Diana Gallagher, head of Biogen’s Alzheimer’s, multiple sclerosis and immunology development units, said: “Our hypothesis is that impacting the CD40L pathway, a central mechanism in immune response, would translate to significant impact on SLE disease burden. These results demonstrate that dapirolizumab pegol has the promise to provide meaningful benefit in this serious, chronic, and often devastating disease.”
The Phase III win was not expected given that in 2018, dapirolizumab pegol missed the primary endpoint of a dose response at 24 weeks on the BICLA scale in a Phase IIb study. However, UCB and Biogen claimed at the time that the study “did demonstrate consistent and potentially meaningful improvements for the majority of clinical endpoints” and adopted the design of the Phase III trial with a longer timepoint in patients with more severe disease.
In a 24 September note, analysts at Jefferies said the results “should come as a surprise to investors given low expectations (40% probability of success) post-mixed Phase II results.” However, the broker, which forecast €400m worldwide peak sales of dapirolizumab pegol, pointed out that PHOENYCS GO “was enriched for patients with low C3/C4, a subgroup which showed a 20%-30% BICLA response over placebo in Phase II.” Lupus patients usually have low C3 and C4 levels during disease flares because of activation of the complement system.
Lupus Space Growing
There has been a surge of interest in the lupus space since the approval of GSK plc‘s Benlysta (belimumab) in 2011. It took another ten years before AstraZeneca PLC‘s type I interferon inhibitor Saphnelo (anifrolumab) got the green light for SLE, while in the same year (2021), Otsuka Pharmaceutical Co. Ltd.‘s calcineurin inhibitor Lupkynis (voclosporin) became the first oral treatment to be approved for lupus nephritis. (Also see "AstraZeneca To Challenge GSK After Clinching Lupus Drug Approval" - Scrip, 3 August, 2021.)
Dapirolizumab pegol is a key drug in Biogen’s plans to diversify from neuroscience to become a major player in immunology. The company is also evaluating the anti-BDCA2 antibody litifilimab in a Phase III for SLE and a Phase II trial for cutaneous lupus erythematosus and in July Biogen completed its $1.15bn acquisition of Human Immunology Biosciences, Inc. (HI-Bio); the purchase centers around felzartamab, a CD38-targeting antibody which is poised to move into Phase III in three indications: primary membranous nephropathy, antibody-mediated rejection and IgA nephropathy. (Also see "Biogen Buys Desired Growth In Immunology With $1.15bn Hi-Bio Deal" - Scrip, 22 May, 2024.)
The PHOENYCS GO announcement is yet more good news this week for UCB. On 23 September, the US Food and Drug Administration approved Bimzelx (bimekizumab), the Belgian group’s blockbuster-in-waiting, for psoriatic arthritis, non-radiographic axial spondyloarthritis and active ankylosing spondylitis, to add to its psoriasis approval. (Also see "Trio Of US Approvals Pushes UCB’s Bimzelx Towards Blockbuster Status" - Scrip, 23 September, 2024.)
