Phase III ADVANCE trial of Vyvgart meets primary endpoint in primary immune thrombocytopenia.

ADVANCE met its primary endpoint demonstrating that a higher proportion of chronic ITP patients receiving Vyvgart achieved a sustained platelet count response compared to placebo. ADVANCE is the first Phase III clinical trial of a neonatal Fc receptor (FcRn) blocker in ITP.

The ADVANCE trial enrolled 131 adult patients with chronic and persistent ITP. Patients were heavily pretreated and 67% of patients had received three or more prior ITP therapies, including 59% who had prior thrombopoietin receptor agonist (TPO-RAs) experience, 34% with prior rituximab experience and 37% with a history of splenectomy. Patients were insufficiently controlled at baseline with mean platelet counts of 17x109/L across all patients.

Of patients who completed the full ADVANCE study, 94% (63/67) of Vyvgart-treated patients and 97% (38/39) of placebo patients continued to the ADVANCE+ open-label extension study. ADVANCE met its primary endpoint demonstrating a significantly higher proportion of patients with chronic ITP receiving Vyvgart (17/78; 21.8%) compared to placebo (2/40; 5%) achieved a sustained platelet response (p=0.0316), defined as having platelet counts greater than or equal to 50x109/L on at least four of the last six scheduled visits between weeks 19 and 24 of treatment. Primary endpoint responders were observed across patient types regardless of age, disease severity, time since diagnosis, prior ITP treatment or background medication.

Key platelet-derived secondary endpoints showed Vyvgart-treated patients had a statistically significant benefit compared to placebo on (1) cumulative number of weeks where platelet counts were at least 50x109/L in the chronic ITP population (p=0.0009) and (2) sustained platelet response in the overall population, including both chronic and persistent ITP patients (p=0.0108). Numerically fewer WHO-classified bleeding events occurred in treated patients throughout the trial but the difference from placebo was not statistically significant. A higher proportion of treated patients in the overall population achieved a durable, sustained platelet response compared to placebo, defined as a sustained platelet response on at least six of the last eight scheduled visits between weeks 17 and 24 of treatment (p=0.0265), but was not considered statistically significant based on hierarchical testing.

Additional secondary endpoint data from the ADVANCE trial are consistent with primary and secondary platelet-derived endpoints and provide additional context on metrics that often drive treatment decisions. Vyvgart was well-tolerated in this 24-week study and the observed safety and tolerability profile was consistent with previous clinical trials.