Argenx Reports Positive Findings in ADHERE Study of Chronic Inflammatory Demyelinating Polyneuropathy

Jeffrey Allen, MD

Vyvgart Hytrulo (Agrenx), a coformulation of efgartigimod alfa and hyaluronidase-qvfc, met its primary end point in the pivotal ADHERE study (NCT04281472) of adults with chronic inflammatory demyelinating polyneuropathy (CIDP), with treated patients showing significantly lower risk of relapse in comparison with placebo.

The primary end point was measured once 88 total relapses or events were achieved in Stage B of the study and was based on the hazard ratio (HR) for the time to first adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) deterioration. All told, treatment with Vyvgart Hytrulo resulted in a 61% reduction in the risk of relapse relative to placebo (P =.000039) while maintaining a safety and tolerability profile that was consistent with previous studies.

"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," Jeffrey Allen, MD, associate professor at the University of Minnesota, said in a statement.¹ "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."

Considered the largest clinical trial of CIDP to date, the study consisted of a run-in period where current treatment was stopped followed by an open-label Stage A, after which responders to Vyvgart Hytrulo advanced to a randomized, placebo-controlled Stage B. In Stage A, 67% of the 322-patient cohort demonstrated evidence of clinical improvement (ECI) after the run-in withdrawal period based on the INCAT Disability Score, the Inflammatory Rasch-built Overall Disability Scale I (I-RODS) or grip strength.

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Additional data from Stage A showed that 70% (214 of 304) demonstrated ECI when excluding those with ongoing treatment at the time of the 88th event who did not have the full opportunity to achieve a response. Sensitivity analysis comprised of those who received at least 4 injections to reach the full immunoglobulin (IgG)-lowering effect of the therapy further raised the number of those demonstrating ECI (78%; 214 of 275). Patients in the study were treatment naïve or on IgG therapy or corticosteroids; however, response rates to Vyvgart Hytrulo remained consistent across all prior CIDP medication subgroups.

"People living with CIDP often experience significant challenges with daily function including fatigue, numbness, tingling, pain and weakness while facing a future with limited mobility or independence," Lisa Butler, executive director, GBS-CIDP Foundation International, said in a statement.¹ "The promising ADHERE data bring hope to the CIDP community of a brighter future where they could experience more positive moments doing the things that make them most happy."

In total, 221 responders from Stage A entered Stage B, where the primary end point was the relative risk of relapse based on time to relapse on the INCAT Disability Score. In addition to meeting the primary end point, findings showed that treated patients had a lower relapse rate compared with placebo at week 24 (26% vs 54%) and week 48 (34% vs 60%). Kaplan-Meier curves showed that patients on active therapy experienced a longer time to relapse, with rapid separation from placebo beginning at week 4 and sustained through week 48.

Vyvgart Hytrulo, a subcutaneous combination of efgartigimod alfa, a human IgG1 antibody fragment, and recombinant human hyaluronidase PH20, Halozyme’s ENHANZE drug delivery technology to facilitate subcutaneous injection delivery of biologics. In terms of safety, the most frequent treatment-related adverse events were injection site reactions, which were mild to moderate and occurred in a lower percentage of patients than previous Vyvgart Hytrulo trials (Stage A: 20%; Stage B: 10%).

REFERENCE
1. Argenx reports positive topline data from ADHERE study of Vyvgart Hytrulo in patients with chronic inflammatory demyelinating polyneuropathy. News release. Argenx. July 17, 2023. Accessed August 8, 2023. https://www.globenewswire.com/news-release/2023/07/17/2705309/0/en/argenx-Reports-Positive-Topline-Data-from-ADHERE-Study-of-VYVGART-Hytrulo-in-Patients-with-Chronic-Inflammatory-Demyelinating-Polyneuropathy.html