Zai Lab Limited announced that the company's partner argenx reported positive data from the Phase 3 ADVANCE trial of VYVGART(R) (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.

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. -- Inrnatitional Working Group (IWG) responder status: 51.2% of YVGART-treated patients were classified as IWGWG 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. Consisntnt safety and tolerability profile ADVANCE is the second registration trial of VYVGART and the firsrst 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.

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. In November 2021, Zai Lab announced that the first patient with primary ITP was treated with efgartigimod in Greater China (mainland China, Hong Kong, Macau, and Taiwan) as part of the global registrational ADVANCE-SC Phase 3 study.

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.