J&J's phase 2 Sjögren's data support FcRn strategy in the autoimmune disorder

The unveiling of Johnson & Johnson’s full data from the phase 2 trial of nipocalimab in Sjögren's disease (SjD) suggest that both the Big Pharma and its competitor argenx are on the right track by targeting FcRn antagonism at the automimmune disorder, according to analysts.

J&J already revealed back in February that its anti-FcRn antibody nipocalimab had scored a win in a phase 2 study in SjD, but it was only at the European Alliance of Associations for Rheumatology (EULAR) 2024 Congress over the weekend that the company finally unveiled the data.

The DAHLIAS study enrolled 163 patients with the autoimmune disease who received either a 5-mg/kg or a 15-mg/kg dose of intravenous nipocalimab every two weeks for 22 weeks, or placebo, alongside standard of care. The data demonstrated a more than 70% improvement in the primary endpoint of a measure of organ disease severity at 24 weeks for patients who received the 15-mg/kg dose compared to the placebo cohort, J&J explained in a presentation.

A response to the treatment was observed as early as Week 4 and continued to increase throughout the 24-week treatment period compared to the placebo group. This follows a phase 3 win for nipocalimab in another autoimmune disorder called generalized myasthenia gravis (gMG) back in February.

The 15-mg/kg cohort also hit secondary endpoints for SjD that involved organ assessments and physician reviews. Improvements were noted in SjD symptoms like dryness of the mouth, eye and vagina. Safety and tolerability were consistent with other clinical studies of nipocalimab.

The 5-mg/kg dose didn’t have a similar impact, however, with J&J noting in its EULAR presentation that this patient cohort clung close to the placebo group in terms of the efficacy endpoints.

“These data establish proof of concept for nipocalimab in Sjögren's disease and support further clinical development, which is welcome news for the approximately four million people worldwide living with this chronic, debilitating disease,” said the study’s investigator Jacques-Eric Gottenberg, M.D., Ph.D., of Strasbourg University Hospital’s Department of Rheumatology, in a June 15 release.

J&J acquired nipocalimab in the $6.5 billion takeover of Momenta Pharmaceuticals in 2020. The deal secured J&J a challenger to now-approved drugs for gMG from argenx and UCB, and a chance to pursue the wide range of indications that could potentially respond to FcRn blockade. Argenx’s failures may have diluted the hype, which had promoted FcRn as the next TNF, but there remain potentially billions of dollars to play for.

Argenx is set to roll out more detailed data from the phase 2 RHO study of its approved anti- FcRn antibody Vyvgart in SjD in July. In a note in response to J&J’s presentation, analysts at William Blair said the opportunity for Vyvgart in SjD will depend on the design of the subsequent phase 3 trial.

“Overall, while there was not much of a dose-response on efficacy outcomes, the high dose of nipocalimab did show a rapid separation from placebo in the primary endpoint of ClinESSDAI (within four weeks) that aligned with the decrease in total IgG and anti-Ro60 and anti-La IgG autoantibodies,” the analysts said in their assessment of J&J’s data.

“While the variability and placebo response rates in SjD do leave some level of risk in future phase 3 trials, the DAHLIAS results do appear to support the FcRN antagonism approach in SjD and argenx’s decision to advance efgartigimod into a phase 3 trial based on an analysis of the results from the RHO study.”