Thursday May 5th 2022



argenx SE (Euronext & Nasdaq: ARGX), a global immunology company committed to improving the lives of people suffering from severe autoimmune diseases, today announced positive data from the Phase 3 ADVANCE trial of VYVGART® (efgartigimod alfa-fcab) in adults with primary ITP. 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 3 clinical trial of a neonatal Fc receptor (FcRn) blocker in ITP.

“Immune thrombocytopenia is a rare, debilitating autoimmune disease that can be very difficult to treat, especially in patients who have an insufficient response to previous ITP therapies. There is no clear standard of care and many patients continue to experience significant symptoms and decreased quality of life,” said Catherine Broome, M.D., Associate Professor of Medicine at Georgetown University Lombardi Comprehensive Cancer Center, and Principal Investigator in the ADVANCE study. “These data are very promising as they show that platelet counts can rapidly improve to clinically meaningful levels following VYVGART treatment in a proportion of a heavily pretreated patient population. We are excited that targeting pathogenic IgG autoantibodies could represent a new, potential approach to help alleviate the disease burden in this patient community.”

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.

Highlights of Phase 3 ADVANCE Data

Primary endpoint met

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 demonstrated statistical significance

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 endpoints provided clinically meaningful data on platelet count responses throughout 24-week trial

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.

  • International Working Group (IWG) responder status: 51.2% of VYVGART-treated patients were classified as IWG responders and 27.9% as complete responders compared to 20% of placebo patients as IWG responders and 4.4% as complete responders. IWG responders are defined as having a platelet count of at least 30x109/L, a two-fold increase in platelet count from baseline, and the absence of bleeding for two separate, consecutive weekly visits. Complete responders are patients with platelet counts of 100x109/L and the absence of bleeding for two separate, consecutive weekly visits.

  • Mean platelet count change from baseline: VYVGART-treated patients demonstrated a rapid onset of platelet count improvement with statistically significant separation from placebo observed at week one and maintained through 20 out of 24 weeks of the trial.

  • Switch to biweekly dosing: Ten VYVGART-treated patients switched to a biweekly (every two weeks) dosing schedule after achieving platelet counts of 100x109/L for three out of four consecutive visits, compared to one placebo patient. Nine of the ten treated patients achieved a sustained platelet response.

Consistent safety and tolerability profile
ADVANCE is the second registrational trial of VYVGART and the first to evaluate chronic weekly dosing. VYVGART was well-tolerated in this 24-week study and the observed safety and tolerability profile was consistent with previous clinical trials.

“In listening to and learning from people in the ITP community, we understand the impact of living with this disease can extend beyond physical signs, taking a serious toll on a person’s quality of life. These compelling preliminary data emphasize the potential for VYVGART to drive responses in ITP regardless of prior lines of therapy, history of splenectomy or time from diagnosis. We look forward to learning more about the potential approach of targeting pathogenic IgGs in ITP through our ADVANCE-SC trial, which is on track to read out in the first quarter of next year,” said Luc Truyen, MD, Ph.D., Chief Medical Officer at argenx. “The totality of data generated thus far continue to support the key attributes of VYVGART, including its onset of action and safety profile. These data further reinforce our confidence in FcRn blockade as a precision tool with the potential to reach a broad spectrum of IgG-mediated severe autoimmune diseases.”

The Phase 3 ADVANCE trial is the first of two registrational trials being conducted as part of the ongoing ITP development program. ADVANCE-SC is evaluating subcutaneous efgartigimod for the treatment of primary ITP. Topline data from the ADVANCE-SC study are expected in the first quarter of 2023.

Phase 3 ADVANCE Trial Design

The Phase 3 ADVANCE trial was a randomized, double-blind, placebo-controlled, multicenter, global trial evaluating the efficacy and safety of VYVGART in adult patients with chronic or persistent primary ITP. A total of 131 adult patients with primary ITP in North America, Europe and Japan enrolled in the trial and received VYVGART or placebo for a total of 24 weeks as part of the primary trial. Enrolled patients had a confirmed ITP diagnosis and a mean entry platelet count of less than 30x109/L. Patients were on a stable dose of at least one ITP treatment prior to randomization and had received at least one prior therapy. Concomitant medications permitted included corticosteroids, nonsteroidal immunosuppressive drugs, fostamatinib or TPO-RAs. If patients were on 'watch and wait' at baseline, they had to have received at least 2 prior treatments for ITP.

Patients were randomized in a 2:1 ratio to receive VYVGART or placebo for a total of 24 weeks as part of the primary trial. Randomized patients received weekly infusions from weeks 1-4 and were eligible to adjust frequency to bi-weekly depending on platelet count. Administration frequency was fixed from study visits 16-24. The primary endpoint was measured by the proportion of patients with chronic ITP with a sustained platelet count response defined as achieving platelet counts of greater than or equal to 50x109/L for at least four of the last six scheduled visits between weeks 19 and 24. Patients who received rescue therapy at week 12 or later, or for whom dose and/or frequency of concurrent ITP therapies increased at week 12 or later, were considered non-responders. Key secondary endpoints included extent of disease control over 24-week treatment period, proportion of overall population with sustained platelet count response, incidence and severity of WHO-classified bleeding events and an extended primary endpoint analysis between weeks 17 and 24.