Argenx Reports Positive Topline Phase 2 Results CIPD Study

Rare Daily Staff

Argenx reported that its ADHERE study evaluating its Vyvgart Hytrulo in adults with the rare autoimmune condition chronic inflammatory demyelinating polyneuropathy met its primary endpoint demonstrating a 61 percent reduction in the risk of relapse compared to placebo.

“CIDP is a chronic, progressive autoimmune disease that can cause substantial disability in those affected, often leading to impaired ambulation or difficulty completing normal daily tasks without help. The positive ADHERE data show that Vyvgart Hytrulo may represent a new patient-forward treatment option that can prevent symptom deterioration while minimizing side effects and treatment burden,” said Jeffrey Allen, associate professor in the Department of Neurology at the University of Minnesota. “With ADHERE, Argenx has set a new standard for innovative CIDP studies that more broadly inform the neuromuscular community. The findings from the trial indicate we may have a novel weapon to combat this debilitating condition in our ongoing efforts to improve the lives of individuals affected by CIDP.”

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare and serious disease of the peripheral nervous system. Although confirmation of disease pathophysiology is still emerging, there is increasing evidence that IgG antibodies play a key role in the damage to the peripheral nerves. People with CIDP experience fatigue, muscle weakness and a loss of feeling in their arms and legs that can get worse over time or may come and go. These symptoms can significantly impair a person’s ability to function in their daily lives. Without treatment, one-third of people living with CIDP will need a wheelchair.

Vyvgart Hytrulo is a subcutaneous combination of efgartigimod alfa, a human IgG1 antibody fragment marketed for intravenous use as Vyvgart, 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), Vyvgart Hytrulo results in the reduction of circulating IgG. It is the first-and-only approved FcRn blocker administered by subcutaneous injection. Vyvgart Hytrulo is approved in the United States to treat generalized myasthenia gravis.

Argenx has an exclusive license agreement with Zai Lab for the development and commercialization of Vyvgart and Vyvgart Hytrulo in Greater China. Through this agreement, Zai Lab recruited Chinese patients into the ADHERE trial.

The ADHERE trial was a multicenter, randomized, double-blind, placebo-controlled trial evaluating Vyvgart Hytrulo for the treatment of CIDP. ADHERE enrolled 322 adult patients with CIDP who were not on active treatment within the past six months or newly diagnosed or being treated with immunoglobulin therapy or corticosteroids. The trial consisted of an open-label Stage A followed by a randomized, placebo-controlled Stage B.

In order to be eligible for the trial, the diagnosis of CIDP was confirmed by an independent panel of experts. Patients entered a run-in stage, where any ongoing CIDP treatment was stopped and in order to be eligible for Stage A had to demonstrate active disease, with clinically meaningful worsening on at least one CIDP clinical assessment tool, including INCAT, I-RODS, or mean grip strength. Treatment naïve patients were able to skip the run-in period with proof of recent worsening. To advance to Stage B, patients needed to demonstrate evidence of clinical improvement (ECI) with Vyvgart Hytrulo. ECI was achieved through improvement of the INCAT score, or improvement on I-RODS or mean grip strength if those scales had demonstrated worsening during the run-in period. In Stage B, patients were randomized to either Vyvgart Hytrulo or placebo for up to 48 weeks.

The primary endpoint was measured once 88 total relapses or events were achieved in Stage B and was based on the hazard ratio for the time to first relapse. After Stage B, all patients had the option to roll-over to an open-label extension study to receive Vyvgart Hytrulo.

Vyvgart Hytrulo was well-tolerated with a safety profile that is consistent with prior clinical trials and the known profile of Vyvgart. The most frequent treatment-related adverse event was injection site reactions, which occurred in a lower percentage of patients than previous Vyvgart Hytrulo trials (20 percent in Stage A; 10 percent in Stage B). All injection site reactions were mild to moderate and resolved over time.

“With these positive ADHERE data, we have generated strong clinical evidence that CIDP has a significant IgG-driven pathogenesis component and that Vyvgart Hytrulo can meaningfully improve and stabilize disease symptoms with a favorable safety profile and a simple route of administration,” said Luc Truyen, chief medical officer of Argenx.

Photo: Luc Truyen, chief medical officer of Argenx