After the unexpected success of their PHOENYCS GO study for dapirolizumab pegol in lupus earlier this fall, Biogen and UCB are planning a second late-stage trial by the end of the year to support a drug application.
Biogen and UCB on Tuesday provided more details regarding their unexpected late-stage victory in the Phase III PHOENYCS GO trial and plotted out a potential regulatory path for their drug candidate dapirolizumab pegol in systemic lupus erythematosus.
In September 2024, the partners announced that PHOENYCS GO hit its primary endpoint but kept specific data under wraps. Expectations were low for dapirolizumab pegol (DZP) given that it failed its Phase II trial in 2018, unable to demonstrate a significant dose response at 24 weeks. But capitalizing on what the companies at the time called “consistent and potentially meaningful improvements” in other endpoints, Biogen and UCB nevertheless decided to push forward with late-stage development of the polyethylene glycol (PEG)-conjugated antigen-binding fragment inhibits. Targeting CD40L signaling, DZP aims to reduce B cell activation and otherwise reduce an overactive immune system.
On Tuesday, Biogen and UCB revealed that patients treated with DZP plus standard of care saw a 49.5% response rate, compared to 34.6% in counterparts receiving standard of care alone. The treatment difference of 14.6% was statistically significant, with a p-value of 0.0110.
“[W]e don’t think investors give any credit to lupus given Biogen’s Ph2b dapi trial was unsuccessful and due to the historic difficulty of treating this multi-component disease,” Truist analysts previously wrote in a note to investors. The firm is waiting for confirmatory data from a second Phase III trial, which could help drive peak penetration of 15% in SLE, with peak global sales of $5.6 billion. The drug is split 50/50 with UCB.
According to the newly announced data, DZP also hit several key secondary endpoints. For instance, patients on DZP showed a 1.8-fold greater improvement in scores in the Systemic Lupus Erythematosus Disease Activity Index 2000 as compared to controls. The treatment effect likewise met statistical significance, with a p-value of 0.0001. In addition, significantly more patients in the treatment group than the placebo arm achieved Lupus Low Disease Activity State at 48 weeks.
Treatment with DZP likewise resulted in greater tapering of corticosteroid treatments commonly taken by patients with lupus, though not significantly so. At 48 weeks, 72.4% of patients in the DZP arm were able to reduce their corticosteroid dose to at most 7.5 mg/day, versus 52.9% in the control arm.
As for safety, DZP was largely well-tolerated with a side effect profile that was consistent with what had been established in previous studies. Of note, serious treatment-emergent adverse events were more frequent in the control arm versus in DZP-treated patients, though more participants in the DZP arm dropped out due to toxicities.
Biogen’s immunology head Diana Gallagher in a statement said that these detailed data from PHOENYCS GO “reinforce our belief that dapirolizumab pegol has the potential to change the approach to care of [systemic lupus erythematosus] and we are dedicated to advancing this program with our partner UCB.”
The partners are preparing to initiate a second Phase III trial by the end of the year, in keeping with the FDA’s guidelines for a drug approval application. The timeline and design for this study have yet to be revealed.
The data drop comes after companies including Bristol Myers Squibb, Kyverna Therapeutics and Cabaletta Bio unveiled details on investigational CAR T therapies for treatment-resistant lupus at American College of Rheumatology Convergence last week, as the industry starts to understand the power of cell therapies to treat autoimmune disease.
