The primary end point has been met in the phase 3 ADVANCE trial which evaluated the efficacy and safety of efgartigimod alfa-fcab in patients with thrombocytopenia.
The phase 3 ADVANCE trial (NCT04188379) evaluating the efficacy and safety of efgartigimod alfa-fcab (Vyvgart) in patients with thrombocytopenia demonstrated a higher proportion of sustained platelet response in patients treated with the agent compared with placebo (P =0.0316), meeting the study’s primary end point.1
According to a press release from Zai Lab Limited, the responders examined in this primary end point were observed across various patient types regardless of age, disease severity, time since diagnosis, prior ITP treatment or background medication.
The randomized, double-blind, placebo-controlled, multicenter ADVANCE trial enrolled a total of 131 adult patients with chronic and persistent primary immune thrombocytopenia (ITP). Patients were randomized 2:1 to receive either efgartigimod alfa-fcab or placebo for 24 weeks as part of the primary trial. From weeks 1-4, the randomized patients received weekly infusions and were eligible to change to receiving it to bi-weekly if their platelet count was fit between study visits 16-24.
Inclusion in the trial was open to patients aged 18 years and older with a confirmed diagnosis of ITP for a minimum of 3 months before randomization. Patients were heavily pretreated, had a diagnosis supported by a response to prior ITP therapy, and 67% of patients received 3 or more prior ITP therapies. This included a total of 59% who had prior thrombopoietin receptor agonist (TPO-RAs) experience, 34% with prior rituximab experience and 37% with a history of splenectomy. Additionally, those enrolled were insufficiently controlled at baseline with mean platelet counts of 17x109/L across all patients.
In addition to the primary end point, the study also evaluated the extent of disease control, number of patients in the overall population with sustained platelet count response or who achieved platelet counts of at least least 50 x 109/L for at least 6 of the 8 visits between week 17 and 24 of the trial, and incidence and severity of the WHO-classified bleeding events as secondary end points.
A total of 94% (63/67) of patients treated with efgartigimod alfa-fcab and 97% (38/39) of those given the placebo completed the study and continued to the ADVANCE+, open-label extension trial.
Findings revealed the study to have met its primary end point by showing a significantly higher proportion of patients with chronic ITP given efgartigimod alfa-fcab (17/78; 21.8%) vs those receiving placebo (2/40; 5%) achieved a sustained platelet response (p=0.0316).
The key platelet-derived secondary end points also showed that those who were treated with efgartigimod alfa-fcab had a statistically significant benefit in comparison to placebo during weeks that the platelet counts were at least 50x109/L in the chronic ITP population (p=0.0009) and that there was sustained platelet response in the overall population, which included both chronic and persistent ITP patients (p=0.0108).
Patients treated with efgartigimod alfa-fcab had fewer WHO-classified bleeding events occur during the trial. However, the difference from those administered the placebo was not statistically significant. Additionally, more patients given efgartigimod alfa-fcab in the overall population achieved a durable, sustained platelet response compared to the placebo group, which was defined as a sustained platelet response on at least 6 of the last 8 scheduled visits between weeks 17 and 24 of treatment (p=0.0265). Based on hierarchical testing, this result also was not considered to be statistically significant.
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.
Other secondary end points showed that 51.2% of efgartigimod alfa-fcab-treated patients were classified as international working group (IWG) responders and 27.9% as complete responders vs 20% of placebo patients as IWG responders and 4.4% as complete responders. IWG responders were those who had a platelet count of at least 30x109/L, a two-fold increase in platelet count from baseline, and the absence of bleeding for 2 separate, weekly visits, while complete responders were defined as patients with platelet counts of 100x109/L who also had an absence of bleeding for 2 consecutive weekly visits.
The mean platelet count change from baseline showed patients treated with efgartigimod alfa-fcab to have a rapid onset of platelet count improvement with statistically significant separation from placebo. This was observed at week 1 of the trial and maintained throughout 20 of the 24 weeks. Additionally, 10 patients treated with efgartigimod alfa-fcab compared to 1 placebo patient ended up switching to a dosing schedule every 2 weeks after they had achieved platelet counts of 100x109/L for 3/4 consecutive visits. Nine of the 10 efgartigimod alfa-fcab-treated patients reported achieving a sustained platelet response.
In regard to safety, the 24-week study showed both the safety and tolerability profiles of efgartigimod alfa-fcab to be consistent with previous clinical trials.
The ADVANCE trial is first of its kind to be a registrational trial with chronic dosing out to 24 weeks, and the second registrational trial of efgartigimod alfa-fcab. It is the first of 2 studies being conducted as part of the ongoing ITP development program. Topline data of the ADVANCE-SC study examining subcutaneous efgartigimod for the treatment of primary ITP is expected to be released in the beginning of 2023.