Argenx’s Vivgart Fails in Late-Stage Trial for Treatment of ITP

Rare Daily Staff

Argenx said the ADVANCE-SC study evaluating Vygart Hytrulo in adults with primary immune thrombocytopenia did not meet the primary endpoint of a sustained platelet count response in chronic ITP patients.

Additional analyses of the dataset are ongoing, and the full results will be presented at an upcoming medical meeting and in a peer-reviewed publication.

“This is not the outcome we had hoped for patients, but setbacks are part of pioneering a new class of medicines and these data will provide insights into the broader understanding of FcRn and ITP,” said Luc Truyen, chief medical officer of Argenx.

Immune thrombocytopenia (ITP) is a rare autoimmune disorder where immunoglobulin G (IgG) autoantibodies destroy platelets and reduce platelet production, which can lead to an increased risk of excessive bleeding and bruising. In rare cases, ITP can lead to severe anemia and life threatening gastrointestinal or intracranial hemorrhages. ITP is also associated with debilitating fatigue and significant impacts on mental health, including anxiety, fear, and depression. Many ITP patients are inadequately controlled on current therapies, so a significant unmet need exists for additional treatment options.

The ADVANCE-SC trial was a randomized, double-blind, placebo-controlled, multicenter, global trial evaluating the efficacy and safety of Vygart Hytrulo in adult patients with chronic or persistent primary ITP. Enrolled patients had a confirmed ITP diagnosis and a mean entry platelet count of less than 30×109/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. The study patients who were on ‘watch and wait’ at baseline were required to have received at least 2 prior treatments for ITP.

Patients were randomized in a 2:1 ratio to receive Vygart Hytrulo or placebo for a total of 24 weeks as part of the primary trial. 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 50×109/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, an extended primary endpoint analysis between weeks 17 and 24, and the incidence and severity of WHO-classified bleeding events.

ADVANCE-SC is the second of two registrational trials conducted as part of the ongoing ITP development program for Vygart and enrolled 207 adult patients with chronic and persistent ITP. Patients were heavily pre-treated, and 75 percent of patients had received three or more prior ITP therapies.

The primary endpoint was not met; 13.7 percent of treated patients demonstrated a sustained platelet count response compared to 16.2 percent of placebo patients.

Secondary endpoints were not met, including additional endpoints on International Working Group responder status and mean platelet count change from baseline.

Vygart Hytrulo was well-tolerated in ADVANCE-SC and the observed safety and tolerability profile was consistent with ADVANCE-IV and the confirmed safety profile of Vygart and Vygart Hytrulo.

Results from the first study in the ITP registrational program, ADVANCE-IV, were reported in May 2022. The study met its primary and key platelet-derived secondary endpoints. ADVANCE-IV formed the basis of the regulatory submission for approval of Vygart IV for ITP in Japan, where a decision is expected in the first quarter of 2024.

Vygart is currently being evaluated in 13 severe autoimmune diseases, including the registrational ADDRESS study for pemphigus from which topline results are expected around year-end 2023.

Vygart Hytrulo is a subcutaneous combination of efgartigimod alfa, a human IgG1 antibody fragment marketed for intravenous use as Vygart, and recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE drug delivery technology to facilitate subcutaneous injection delivery of biologics. In binding to the neonatal Fc receptor (FcRn), Vygart Hytrulo results in the reduction of circulating IgG.

Vygart Hytrulo is the proprietary name in the U.S. for subcutaneous efgartigimod alfa and recombinant human hyaluronidase PH20. It is marketed in Europe as Vygart and may be marketed under different proprietary names following approval in other regions.

Photo: Luc Truyen, chief medical officer of Argenx