Dapirolizumab pegol seen to reduce SLE disease activity in Phase 3 trial
Developers: Results show therapy may 'change the approach' to lupus care
Treatment with dapirolizumab pegol is better than a placebo at controlling disease activity in people with systemic lupus erythematosus (SLE), according to new results from a Phase 3 clinical trial.
UCB and Biogen, the therapy’s developers, shared full results from that trial — which they called “statistically and clinically significant” — in a late-breaking presentation at the American College of Rheumatology’s annual meeting, held Nov. 14-19 in Washington, D.C. The presentation was titled “Dapirolizumab Pegol Demonstrated Significant Improvement in Systemic Lupus Erythematosus Disease Activity: Efficacy and Safety Results of a Phase 3 Trial.”
According to the developers, 50% less severe disease flares were seen in patients given the experimental therapy relative to participants on standard of care treatment alone.
“These results reinforce our belief that dapirolizumab pegol has the potential to change the approach to care of SLE and we are dedicated to advancing this program,” Diana Gallagher, MD, lead of the Alzheimer’s disease, multiple sclerosis, and immunology development units at Biogen, said in a press release from the two companies.
Dapirolizumab pegol meets goal in PHOENYCS GO study
Dapirolizumab pegol is designed to block CD40L signaling — a molecular pathway that’s involved in the activation of immune cells that drive the autoimmune attack that causes lupus.
Fiona du Monceau, head of patient evidence at UCB, said “progress in the treatment of lupus has historically been challenging,” citing as one reason the “the varied symptoms and severity” seen in patients. du Monceau also noted that women are “disproportionately affected by lupus.”
“With dapirolizumab pegol, we believe that our differentiated approach that targets the CD40L pathway results in clinically meaningful improvements across multiple disease domains and could substantially impact the burden of this disease in particular for women,” du Monceau.
A Phase 3 clinical trial called PHOENYCS GO (NCT04294667) tested the therapy in 321 people with SLE. Participants were randomly assigned to receive dapirolizumab pegol or a placebo, both administered intravenously, or into the bloodstream, once every four months for 48 weeks, or nearly one year, in addition to standard of care treatments.
The trial’s main goal was to see if more patients given the experimental therapy achieved a response on the British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA), essentially reflecting a reduction in lupus disease activity. The results showed that the study met this goal, with significantly more patients given the medication achieving a BICLA response at 48 weeks than those on the placebo (49.5% vs. 34.6%).
The rate of BICLA response after 24 weeks, or nearly six months, was slightly higher with dapirolizumab pegol than with the placebo, though at this earlier time point the difference was not considered statistically significant.
Other measures of disease activity, including the SLE Responder Index (SRI)-4 response, the Lupus Low Disease Activity State (LLDAS), and the SLE Disease Activity Index-2K (SLEDAI-2K), also showed significant differences favoring therapy over the placebo at 48 weeks.
According to Megan E.B. Clowse, MD, principal investigator of the study and a professor at the Duke University School of Medicine in North Carolina, “there remains a significant unmet need for additional treatment options” for SLE patients.
“The results we observed in PHOENYCS GO suggest dapirolizumab pegol has the potential to be impactful for this chronic and debilitating autoimmune disease,” Clowse said. “Across clinical endpoints we observed a positive effect.”
Developers planning to further test therapy in second Phase 3 trial
Over the course of the study, which spanned 48 weeks, patients given dapirolizumab pegol had about 50% fewer severe disease flares — episodes in which symptoms suddenly worsen — compared with those given the placebo (11.6% vs. 23.4%).
Importantly, significantly more patients given dapirolizumab pegol (72.4% vs. 52.9%) were able to reduce their dosage of corticosteroids — to 7.5 mg/day or less at week 48. Corticosteroids are powerful anti-inflammatory medications commonly used to help manage lupus. However, these drugs can cause problematic side effects, particularly when administered at high doses for a prolonged period of time.
“Participants receiving dapirolizumab pegol experienced reduced lupus activity while also tapering steroids, changes important to people living with the disease,” Clowse said.
Rates of treatment-emergent adverse events were slightly higher among patients given dapirolizumab pegol (82.6% vs. 75%). However, the rates of serious treatment-emergent adverse events were lower in patients given the experimental therapy (9.9% vs. 14.8%).
The percentage of patients who stopped treatment due to safety issues was similar in both groups: 4.7%, or 10 patients, on dapirolizumab pegol, and 3.7%, or four patients, on the placebo.
Participants receiving dapirolizumab pegol experienced reduced lupus activity while also tapering steroids, changes important to people living with the disease.
Opportunistic infections — a potential concern with any immune-suppressing therapy — were reported in 2.8% of participants receiving the therapy and in 0.9% of those given the placebo. Overall, dapirolizumab pegol “was generally well tolerated,” according to the researchers.
UCB and Biogen are planning to further test the treatment candidate in a second Phase 3 clinical trial, PHOENYCS FLY (NCT06617325). No study sites have been announced, and the trial has not yet begun recruiting participants. It will similarly test dapirolizumab pegol against a placebo in people with SLE, ages 16 and older, with moderate to severe disease activity.
“We are highly encouraged by the results we have seen in PHOENYCS GO and are excited to continue the clinical development of dapirolizumab pegol in the second Phase 3 study, PHOENYCS FLY,” du Monceau said.
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