When it rains, it pours, as new mechanisms of action make their mark in lupus nephritis and moderate-severe disease.
Two phase-three drug trials have shown significant improvements in disease activity in SLE patients taking dapirolizumab pegol and lupus nephritis patients given obinutuzumab.
One multicentre, randomised, double-blind, placebo-controlled parallel-group study included 321 participants with moderate-to-severe systemic lupus erythematosus (SLE).
The phase three PHOENYCS GO trial compared dapirolizumab pegol – a novel Fc-free anti-CD40L drug candidate – plus standard of care to placebo plus standard of care.
The researchers found that participants who took dapirolizumab pegol had greater improvement of moderate-to-severe disease activity after 48 weeks compared with patients in the placebo group.
The participants’ disease activity was assessed according to the British Isles Lupus Assessment Group-based Composite Lupus Assessment.
According to drug manufacturer partners Biogen and UCB, dapirolizumab pegol inhibits CD40L signalling, reducing B cell activation and autoantibody production, mitigating type 1 interferon secretion and attenuating T cell and antigen-presenting cell activation.
Fiona du Monceau, Head of Patient Evidence at UCB, said the results were “encouraging”.
“We have confidence in the unique mode of action of dapirolizumab pegol which targets multiple inflammatory pathways involved in the pathogenesis of SLE,” she said.
The participants will continue to be followed up long term, the drug manufacturers said.
Meanwhile, the phase three REGENCY study involving patients with active lupus nephritis found that a higher proportion of people treated with obinutuzumab (Gazyva) plus standard therapy achieved a complete renal response at 76 weeks compared to those treated with standard therapy (mycophenolate mofetil and glucocorticoids) alone.
Obinutuzumab is an intravenous immunotherapy drug usually used to treat follicular lymphoma and chronic lymphocytic leukemia.
The researchers also found that a statistically significant proportion of patients achieved complete renal response with a successful reduction of corticosteroid use at 76 weeks, and an improvement in proteinuric response also at 76 weeks. “Data suggest that Gazyva depletes disease-causing B cells, helping to limit further damage to the kidneys and potentially preventing or delaying progression to end-stage kidney disease,” manufacturer Genentech said in a statement.
