Data at EULAR back Biogen, UCB's first-in-class lupus drug

 Full results from the first phase 3 trial of UCB and Biogen's anti-CD40L antibody dapirolizumab pegol (DZP) in systemic lupus erythematosus (SLE) have been revealed, and have not disappointed.

Presented at the EULAR congress in Barcelona this week, the PHOENYCS GO study in moderate to severe, treatment-refractory SLE patients showed significant improvements when DZP was added to standard treatment on a wide range of symptoms and markers of disease activity.

SLE is a chronic and highly debilitating autoimmune disease that affects multiple organ systems – with a range of symptoms extending from rash and arthritis to seizures and psychosis – and disproportionately affects women, with around 200,000 people living with the condition in the US alone.

After 48 weeks, 40.9% of patients treated with DZP in PHOENYCS GO achieved the Lupus Low Disease Activity State (LLDAS) endpoint, which means that they were showing no disease activity in major organ systems and no other symptoms like anaemia, compared to 19.6% of those assigned to standard treatment plus placebo.

All told, 19.2% of the DZP group obtained complete remission at that timepoint, versus 8.4% of the placebo group, according to study investigator Eric Morand of Monash Hospital in Australia, who presented the data at EULAR. There were also signs that patients needed lower doses of steroids, which are a standard therapy for SE, but can have serious side effects, especially when used long term.

A second trial will be needed before UCB and Biogen can file DZP with regulators, and the PHOENYCS FLY study is currently underway with results due in 2027.

Morand said that the drug "has the potential to become a significant new medication for people living with SLE […] and I look forward to seeing results from the second phase 3 study."

Meanwhile, DZP-treated patients showed consistent improvements in fatigue, a common and debilitating symptom of SLE, on the FACIT-Fatigue and FATIGUE-PRO, which were significantly better than the control group, according to Ioannis Parodis of Karolinska University Hospital in Sweden.

Fatigue is a common manifestation of SLE, but is "a difficult-to-treat symptom that can severely impact a person's quality of life, and remains a challenge to address," he said. "The results we observed in this phase 3 study indicate that participants treated with [DZP] have the potential to achieve consistent improvements in fatigue beyond the current standard of care."

Other CD40L-directed therapies in the industry pipeline include Sanofi's frexalimab – in phase 3 for multiple sclerosis and phase 2 for SLE and type 1 diabetes – and Novartis' iscalimab, which was in testing for various indications, including SLE, but now only has Sjogren's syndrome listed in Novartis' latest pipeline update.

Merck's enpatoran heading for phase 3

Also at EULAR, Merck KGaA presented phase 2 data with its oral TLR7/8 inhibitor enpatoran in SLE, saying that it intends to start a phase 3 programme for the drug in some forms of the disease, even though the drug missed the primary endpoint in the study.

Data from Cohort B of the WILLOW trial showed that enpatoran achieved improvements in measures of both systemic and cutaneous disease activity in prespecified SLE subpopulations despite standard of care, measured using the BICLA scale.

The overall population did not see a statistically significant improvement on that measure, although, patients with skin involvement – either cutaneous SLE or SLE with active rash – saw a greater, significant benefit with a response rate of 58.6% versus 31.7% for placebo.

Skin manifestations of SLE "are often part of the systemic activity or flare, which can be painful and have a considerable impact on quality of life," said Morand.

Merck said it will now start discussions with regulatory authorities to try to define a route to approval for enpatoran in SLE.

https://pharmaphorum.com/news/data-eular-back-biogen-ucbs-first-class-lupus-drug