EULAR 26 hears of treatment advances in lupus

New trial data with Johnson & Johnson's nipocalimab, Biogen and UCB's dapirolizumab pegol, and Merck KGaA's enpatoran have raised hopes of a new generation of targeted treatments for systemic lupus erythematosus (SLE).

The new results – reported at the European Alliance of Associations for Rheumatology (EULAR) conference in London – are all for potentially first-in-class therapies for SLE, a chronic autoimmune disease that occurs when the body's immune system mistakenly attacks its own healthy tissues, affecting three to five million people worldwide.

The data comes from the phase 2 JASMINE study of J&J's FcRn inhibitor nipocalimab, the phase 3 PHOENYCS GO trial of Biogen and UCB's CD40L signalling inhibitor dapirolizumab pegol (DZP), and a long-term extension to the midstage WILLOW study of Merck's TLR 7/8 inhibitor enpatoran.

JASMINE is first trial to show benefit of FcRn blockade

Nipocalimab – already approved as Imaavy for generalised myasthenia gravis (gMG) and the first drug in the FcRn inhibitor class to be studied in SLE – met its primary objective by achieving a significant reduction in disease activity at 24 weeks, measured using the SRI-4 and LLDAS scales, that was maintained out to 52 weeks.

A 15 mg/kg dose of nipocalimab, given on top of background medication, achieved an SRI-4 response in 53.5% of patients at week 24, compared to 46.7% of those getting background therapy and placebo, while at 52 weeks the rate came in at 53.6% and 39.7%, respectively. At the latter time point, the LLDAS response rate was 37.5% with nipocalimab compared to 20.5% with placebo.

The study showed a consistent response with the FcRn blocker across patients with different levels of disease activity, with greater benefit seen in those with higher levels of pathogenic autoantibodies, and provided proof-of-concept for the drug's mechanism in SLE. J&J is currently recruiting patients into the phase 3 GARDENIA study of nipocalimab in SLE, which should generate results in 2028.

PHOENYCS GO builds the case for DZP with reduced flares

Data from the PHOENYCS GO study of DZP caused a stir at last year's EULAR conference in Barcelona, including an LLDAS response of 40.9% with the drug versus 19.6% with placebo, both given on top of background treatment, at 48 weeks. In London, UCB and Biogen added to the evidence for the drug with new results showing that patients were able to reduce their steroid use with DZP and still maintain their response.

The results also revealed that compared to placebo, DZP treatment reduced the number of moderate or moderate/severe 'flares' – periods when disease activity suddenly spikes – measured using the BILAG-2004 score, while more patients treated with the CD40L-targeting drug were flare-free over the 48 -week follow-up period.

UCB and Biogen are also running a confirmatory phase 3 trial, PHOENYCS FLY, with a readout due in 2028.

WILLOW finds long-term benefit with enpatoran

Merck recently started its phase 3 programme for enpatoran, which is being developed for the 85% of people with SLE who have skin manifestations of the disease, with the first patients dosed in the ELOWEN-1 and ELOWEN-2 trials. At EULAR, there was an update on the results of the phase 2 WILLOW trial, specifically a long-term extension study out to 48 weeks in subjects who had completed the initial 24-week stage reported last year.

Enpatoran continued to provide clinically meaningful improvement in cutaneous disease activity, including high rates of responses on the CLASI-70 cutaneous disease activity scale. At 48 weeks, around 75% of the patients treated with the highest dose of the TLR 7/8 inhibitor saw a 50% to 70% improvement in skin activity scores.

All three new agents are hoping to join a growing number of targeted therapies that have started to increase treatment options for SLE patients in recent years, such as GSK's BLyS inhibitor Benlysta (belimumab), AstraZeneca's type I interferon receptor antagonist Saphnelo (anifrolumab), and Roche's anti-CD20 therapy Gazyva/Gazyvaro (obinutuzumab).

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