Zai Lab and argenx Report Positive Topline Data from ADHERE Study of VYVGART Hytrulo in Patients with Chronic Inflammatory Demyelinating Polyneuropathy
- Study met primary endpoint (p=0.000039); VYVGART® Hytrulo demonstrated 61% reduction (HR: 0.39 95% CI: 0.25; 0.61) in risk of relapse versus placebo
- IgG autoantibodies shown to play significant role in underlying CIDP disease biology
- Favorable safety and tolerability profile consistent with previous clinical trials and confirmed safety profile of VYVGART®
Zai Labenrolled a significant number of patients in the Greater Chinaportion of the global ADHERE study
- 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 rare chronic immune-mediated peripheral neuropathy characterized by weakness and sensory dysfunction in the limbs, significantly impacting the daily life and work of patients,” said Dr. Chongbo Zhao, M.D., Ph.D., Deputy Director of
“The positive ADHERE trial data provides strong clinical evidence that VYVGART Hytrulo meaningfully improves and stabilizes disease symptoms in CIDP patients with a favorable safety profile and a simple route of administration,” said Dr.
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.
About ADHERE Trial Design
The ADHERE trial was a multicenter, randomized, double-blind, placebo-controlled trial evaluating VYVGART® Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP). ADHERE enrolled 322 adult patients with CIDP who were treatment naïve (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 adjusted INCAT deterioration (i.e. relapse). After Stage B, all patients had the option to roll-over to an open-label extension study to receive VYVGART Hytrulo.
About Chronic Inflammatory Demyelinating Polyneuropathy
Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare and serious autoimmune 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.
About CIDP in
The prevalence of CIDP in
1 Chronic inflammatory demyelinating polyneuropathy and diabetes, 2020.
About VYVGART® Hytrulo
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 the proprietary name in the
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