ALLEGORY NEJM Readout: Obinutuzumab Reports SRI‑4 and Steroid‑Sparing Benefits

Roche reported that the phase III ALLEGORY study in systemic lupus erythematosus (SLE) met its prespecified primary endpoint at week 52, and that all five key secondary endpoints were also met, including sustained glucocorticoid reduction on a background of standard therapy.

The company’s description centers on obinutuzumab (Gazyva/Gazyvaro) versus placebo, with outcomes presented at the 52-week assessment. Roche also referenced its safety characterization and said it is engaged in regulatory discussions related to the dataset. The update framed the readout as an efficacy-and-safety summary alongside ongoing interactions with health authorities.

For the primary comparison at week 52, Roche described obinutuzumab plus standard therapy versus placebo plus standard therapy and reported the SLE Responder Index-4 (SRI-4) result as follows: 76.7% in the obinutuzumab arm versus 53.5% in the placebo arm, with an adjusted difference of 23.1 percentage points (95% CI, 12.5 to 33.6; p<0.001). The company presented these data as the prespecified primary endpoint for the phase III trial. In Roche’s account, the primary analysis was anchored to the week-52 timepoint for the between-group comparison, and the release described a statistically significant difference in SRI-4 response at that prespecified assessment.

Roche also highlighted a glucocorticoid-focused key secondary endpoint assessing reduction to ≤7.5 mg/day sustained from week 40 through week 52. For this endpoint, the company reported 80.0% in the obinutuzumab group and 54.1% in the placebo group, with an adjusted difference of 30.2 percentage points (95% CI, 15.3 to 45.1; p<0.001). This outcome was presented alongside other key secondary endpoints as part of the company’s week-52 dataset summary. Roche framed the endpoint as sustained glucocorticoid reduction over the prespecified week-40-to-52 window.

Roche stated that all five key secondary endpoints were met and reported additional measures of disease control. These included BICLA response at week 52 (62.0% with obinutuzumab vs 40.1% with placebo; adjusted difference 21.9 percentage points; p<0.001) and SRI-4 response at week 40 sustained to week 52 (72.0% vs 46.4%; adjusted difference 25.4 percentage points; p<0.001). The company also reported SRI-6 response at week 52 as 68.9% versus 38.9% (adjusted difference 30.0 percentage points; p<0.001).

Additional measures included time to first BILAG-defined flare through week 52, reported with a hazard ratio of 0.58 (95% CI, 0.40 to 0.82; p=0.002), and DORIS remission at week 52, reported as 35.1% with obinutuzumab versus 13.8% with placebo (adjusted difference 21.2 percentage points; 95% CI, 11.8 to 30.5). In Roche’s reporting, these outcomes were presented as measures of disease activity control across the study follow-up period, with timepoints and sustained-response windows defined for individual endpoints.

Roche described ALLEGORY as enrolling approximately 300 participants with 1:1 randomization, a treatment period up to 52 weeks, and an open-label extension up to 104 weeks, consistent with the registry listing for the ALLEGORY trial (NCT04963296). In its safety language, the company stated that findings were consistent with the well-characterised profile of obinutuzumab and that no new safety signals were identified. Roche also said the ALLEGORY data are being discussed with the US Food and Drug Administration and the European Medicines Agency and that it intends to work with regulators toward availability. The company also noted that, if approved, obinutuzumab could become the first Type II anti-CD20 therapy for SLE, directly targeting B cells involved in disease activity.

Key Takeaways:

• Roche reported that ALLEGORY met its prespecified SRI-4 primary endpoint at week 52, with a higher responder proportion in the obinutuzumab arm than in the placebo arm on a standard-therapy background.
• All five key secondary endpoints were reported as met, including BICLA response at week 52, sustained SRI-4 response from week 40 to 52, SRI-6 response at week 52, glucocorticoid reduction sustained from week 40 to 52, and time to first BILAG-defined flare through week 52.
• Roche reported additional disease-control outcomes, including DORIS remission at week 52, and stated there were no new safety signals, alongside ongoing discussions with regulators regarding potential availability.