Boosting platelet counts in ITP is aim of efgartigimod study
Phase 3 ADVANCE-NEXT trial seeks to enroll about 63 adults
A Phase 3 trial testing efgartigimod administered into a vein in adults with primary immune thrombocytopenia (ITP) is still enrolling participants and its top-line results are due in the second half of next year.
Called ADVANCE-NEXT (NCT06544499), the study seeks around 63 adults with primary ITP that’s lasted for more than a year and who’ve had an insufficient response to at least one previous ITP treatment. It’s enrolling at sites in the U.S., Europe, and China. The results may support a request to U.S. regulators of the therapy’s approval for ITP, according to Argenx, its developer. Efgartigimod is approved for adults with ITP in Japan, where it’s sold as Vyvgart.
Argenx already markets Vyvgart Hytrulo, a subcutaneous, or under-the-skin, formulation of efgartigimod, in the U.S. and elsewhere for certain autoimmune conditions, including generalized myasthenia gravis (gMG), and is investigating its potential for several others. The company reported it’s studying the therapy across 15 autoimmune diseases.
“Vyvgart is delivering strong growth across all indications, formulations and regions,” Tim Van Hauwermeiren, Argenx’s CEO, said in a company update. “With six registrational and six proof-of-concept readouts expected by the end of 2026, we are executing on our proven innovation playbook that is … aimed at transforming care for patients with high unmet need.”
In ITP, the immune system mistakenly produces self-reactive antibodies that target the cell fragments called platelets that are needed to promote blood clotting after an injury, leading to their destruction. In primary ITP, there’s no known underlying cause or trigger for the condition. Patients are prone to excessive internal or external bleeding.
Results of Vyvgart studies
Vyvgart belongs to a class of therapies called FcRn blockers, which lower levels of the harmful antibodies that drive autoimmune diseases by inhibiting neonatal Fc receptor (FcRn). The protein normally helps stabilize and prevent the destruction of circulating antibodies belonging to the immunoglobulin G class, including the self-reactive ones that drive ITP and other autoimmune conditions. By inhibiting FcRn, Vyvgart seeks to accelerate their breakdown and ease disease symptoms.
Vyvgart’s approval for ITP in Japan was supported by findings from the Phase 3 ADVANCE-IV trial (NCT04188379), which involved adults with persistent or chronic primary ITP who were either on an ITP treatment and had received at least one previous therapy or who weren’t on current treatment, but had received at least two prior therapies. Its participants received weekly infusions of Vyvgart or a placebo for four weeks. After that, the dosing schedule was adjusted based on platelet responses.
Results showed Vyvgart was well tolerated and significantly more participants on Vyvgart achieved a sustained platelet count response than in the placebo group. A significantly greater median number of weeks of disease control was also observed with Vyvgart. The study’s participants are now receiving long-term treatment with Vyvgart in an open-label extension trial called ADVANCE+ (NCT04225156).
In ADVANCE-NEXT, adults with ITP will be randomly assigned to infusions of Vyvgart or a placebo for up to about six months. After the main trial, there will be two consecutive open-label treatment periods, each a year long, where all will receive Vyvgart. The study will end with a two-month follow-up without treatment.
The main goal is to evaluate the extent of disease control in the first six months, defined as the number of weeks during which platelet counts reach at least 50 billion platelets per liter, a level believed to substantially lower the risk of clinically significant bleeding. Other ways of measuring platelet responses, rates of rescue therapy, incidence of bleeding, and safety will also be evaluated.
The subcutaneous formulation of efgartigimod was also tested in people with ITP in a Phase 3 trial called ADVANCE SC (NCT04687072), but the study failed to meet its primary and secondary efficacy goals. An open-label extension study called ADVANCE SC+ (NCT04812925) may still be ongoing.
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