argenx reports positive topline data from ADHERE study of VYVGART Hytrulo in patients with chronic inflammatory demyelinating polyneuropathy

ADHERE Highlights

• Primary endpoint met (p=0.000039); VYVGART Hytrulo demonstrated 61% reduction (HR: 0.39 95% CI: 0.25; 0.61) in the risk of relapse versus placebo

• 67% of patients in open-label Stage A demonstrated evidence of clinical improvement (ECI), indicating that IgG autoantibodies play a significant role in the underlying biology of CIDP

• Safety and tolerability profile consistent with confirmed safety profile of VYVGART

• 91% (226/249) of eligible patients continued to the ADHERE-Plus open-label extension study

"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,” commented Jeffrey Allen, M.D., Associate Professor, Department of Neurology, 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.”

“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. 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,” said Lisa Butler, Executive Director of the GBS-CIDP Foundation International.

“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,” commented Luc Truyen, M.D., Ph.D., Chief Medical Officer of argenx. “We are very grateful to the patients participating in the ADHERE trial and their supporters, the investigators, our collaborators and our argenx colleagues for the success of this innovative trial. Together, we are moving one step closer to transforming the treatment of autoimmunity.”

Detailed ADHERE Results

ADHERE is the largest clinical trial of CIDP patients to date, enrolling adults who were treatment naïve (not on active treatment within the past six months) or currently on immunoglobulin therapy or corticosteroids. The trial 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.

322 patients enrolled in Stage A and received treatment with VYVGART Hytrulo

• 67% (214/322) demonstrated evidence of clinical improvement (ECI) after a run-in withdrawal period based on the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score, the Inflammatory Rasch-built Overall Disability Scale (I-RODS) or grip strength

• 70% (214/304) demonstrated ECI excluding patients ongoing in Stage A at the time of the 88th event who did not have the full opportunity to achieve a response

• 78% (214/275) demonstrated ECI in a sensitivity analysis of patients who received at least four injections to reach the full IgG-lowering effect of VYVGART Hytrulo

• Response rates similar across all prior CIDP medication subgroups with consistent efficacy on INCAT, I-RODS and grip strength.

221 responders from Stage A entered Stage B, where the primary endpoint was the relative risk of relapse based on time to relapse on the INCAT Disability Score

• VYVGART Hytrulo significantly reduced the risk of CIDP relapse compared to placebo

  • Primary endpoint was met (p=0.000039); VYVGART Hytrulo demonstrated a 61% reduction (HR: 0.39 95% CI: 0.25; 0.61) in the risk of relapse compared to placebo based on time to the first adjusted INCAT deterioration of ≥1 point

  • VYVGART Hytrulo patients had a lower relapse rate compared to placebo at Week 24 (26% versus 54%) and Week 48 (34% versus 60%)

  • VYVGART Hytrulo patients experienced longer time to relapse compared to those on placebo with a rapid separation of the Kaplan–Meier curves beginning at Week 4 and sustained through Week 48

  • VYVGART Hytrulo patients demonstrated a clinically meaningful mean improvement of 7.7 points on I-RODS and 12.3kPa on grip strength in Stage A. This clinically meaningful benefit was maintained in Stage B by treated patients and lost in placebo patients.

  • Clinical benefit observed across all efficacy scales and patient subgroups, regardless of prior therapy

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 (ISRs), which occurred in a lower percentage of patients than previous VYVGART Hytrulo trials (20% in Stage A; 10% in Stage B). All ISRs were mild to moderate and resolved over time.