argenx reports topline results from ADDRESS study of efgartigimod SC in pemphigus

The ADDRESS results show the proportion of PV patients achieving the primary endpoint of complete remission on a minimal dose of steroids (CRmin) was not significantly different between efgartigimod SC and placebo. argenx will not pursue additional development in pemphigus and plans to prioritize clinical development of efgartigimod in its ongoing severe autoimmune indications.

“We are disappointed by today’s results, particularly for pemphigus patients who have seen little innovation in this treatment space,” said Luc Truyen, M.D., Ph.D., Chief Medical Officer at argenx. “At argenx, we are in the business of transformation, providing new medicines that go beyond incremental benefit and raise the bar for what patients can expect from a treatment. While we will not move forward into pemphigus, our job today is the same as yesterday – continue to be execution-focused and data-driven, apply learnings across our ongoing development programs, and pursue optimal development of efgartigimod, empasiprubart and our earlier stage programs. 2023 was a remarkable year of growth for argenx across the business and we are poised to build on our success in 2024.

ADDRESS Study Results; The Phase III ADDRESS study enrolled 222 adult patients with newly diagnosed or relapsing moderate-to-severe PV (n=190) or PF (n=32). Patients were randomized to efgartigimod SC or placebo with both treatment groups receiving concomitant steroids at a starting dose of 0.5mg/kg, which is a lower dose than recommended by current treatment guidelines and was tapered according to protocol upon achievement of complete remission.

Consistent pharmacodynamic (PD) effect of efgartigimod SC: Treatment with efgartigimod SC led to total immunoglobulin G (IgG) and desmoglein autoantibody (DSG-1 and DSG-3) reductions up to 75%. The observed PD effect was consistent with previous clinical trials of efgartigimod.

Unexpected PD effect of corticosteroids: There was a higher than expected response to background treatment with corticosteroids, which showed a reduction of DSG-1 and DSG-3 levels of up to 70% in the placebo arm and correlated to sustained clinical benefit. The level of autoantibody reduction driven by corticosteroids in both treatment arms was sufficient for patients to achieve CRmin. The significant PD effect of corticosteroids was specific to DSG-1 and DSG-3 autoantibodies, while the observed effect on total IgG reduction was in line with the literature (up to 10%).

Study did not meet primary endpoint: Treatment with efgartigimod SC led to CRmin in 35.5% (44/124) of patients compared to 30.3% (20/66) with placebo (p=0.5956). Secondary endpoints were also not met, including CRmin in the overall pemphigus population (PV and PF), cumulative dose of corticosteroids and time to disease control or complete remission. Consistent and favorable safety profile: Efgartigimod SC was well-tolerated in ADDRESS. The observed safety and tolerability profile was consistent with other clinical trials and the confirmed safety profile of VYVGART and VYVGART Hytrulo.

Update on BALLAD Study: argenx is reviewing the BALLAD study in light of the ADDRESS results and the comparable biology between pemphigus and bullous pemphigoid, and has decided not to make a GO/NO GO decision at this time but rather wait for learnings from all currently enrolled patients and consider a new trial design for the path forward.