Vyvgart Hytrulo Challenges the Step Therapy Model in Treatment-Naive CIDP

Post hoc ADHERE analysis at AAN 2026 shows that Vyvgart Hytrulo produces a confirmed early response in 87.5% of treatment-naive chronic inflammatory demyelinating polyneuropathy (CIDP) patients, raising questions for payers about step-therapy policies.

Post Hoc Analysis at AAN

A post hoc analysis of the ADHERE study, presented at the 2026 AAN Annual Meeting, provides Argenx with data to support an earlier positioning of Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc, the subcutaneous formulation) in chronic inflammatory demyelinating polyneuropathy (CIDP), potentially ahead of intravenous immunoglobulin (IVIG) rather than after it. The analysis showed that 87.5% of treatment-naive CIDP patients who received Vyvgart Hytrulo achieved confirmed clinical response, with the benefit emerging early in the treatment course.

Why It Matters

Real-World Burden of CIDP

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune neuropathy characterized by progressive weakness and impaired sensory function, affecting an estimated 40,000 to 100,000 patients in the United States. CIDP is a rare but debilitating autoimmune disorder that attacks the peripheral nervous system. While standard treatments exist, a recent real-world study sheds light on the significant challenges patients face when initial therapies fail.

Research focused on the real-world burden of CIDP is crucial because it addresses a major gap in our understanding of refractory CIDP—patients who do not respond adequately to initial treatment. While clinical trials often show promising results, real-world data reveals a more complex picture. The research highlights a significant unmet need: approximately 31% of patients switch their first-line treatment (LOT1) within just two years. For these patients, the honeymoon period of treatment is brief and the median time to switch is only 5.6 months. Perhaps most concerning is that as patients move to subsequent lines of therapy, the duration they stay on those treatments drops drastically to just 1–3 months, suggesting that once a patient fails their first treatment, finding an effective alternative becomes increasingly difficult.

Historic and New Therapies

IVIG has historically served as first-line therapy, with Vyvgart Hytrulo currently positioned following IVIG failure or intolerance in many managed care coverage policies. The ADHERE post hoc data directly challenge that sequencing by showing that patients who arrive at Vyvgart Hytrulo without prior treatment history achieve high response rates quickly, suggesting that delaying access to the subcutaneous FcRn inhibitor through mandated IVIG trials may not be clinically necessary for all patients.

Who It Affects

What Real-World Data Says

CIDP predominantly affects older adults and is more common in men than women. In a real-world study assessing real-world burden of CIDP, the cohort included 1,942 patients:

• 75% were aged 50 or older.
• 54% were male.
• 86% were white.

The burden on these individuals is heavy. Beyond the physical symptoms like leg weakness and loss of balance, the study found that 40% of patients required hospitalization within two years of starting treatment. Those in the refractory group (who switched treatments) faced an even higher burden, averaging 45.3 healthcare visits per year, compared to 35.3 visits for those who stayed on their initial therapy.

The Evolving Picture of CIDP: Understanding the Statistics and Epidemiology

CIDP is a complex, immune-mediated disorder of the peripheral nervous system. While it is often described as the chronic counterpart to Guillain-Barré Syndrome, CIDP has a distinct epidemiological profile and a statistical footprint that highlights the significant burden it places on patients. Understanding these figures is essential for improving diagnosis and directing healthcare resources to those in need.

Epidemiological data reveals that CIDP is not an equal-opportunity disorder. It shows a clear preference in terms of gender and age:

• Gender Disparity: Men are significantly more likely to be diagnosed than women, with a reported ratio of approximately 2:1.
• The Age Factor: While CIDP can occur in children, it is primarily a disease of advancing age. The mean age at diagnosis is approximately 60 years old, and the incidence of the condition increases as people get older.

Prevalence and Incidence: Measuring the Reach

CIDP is classified as a rare disease, but its prevalence varies significantly across different studies and regions:

• Incidence Rate: Recent meta-analyses suggest a crude incidence rate of approximately 0.3 per 100,000 individuals per year.
• Prevalence Range: The overall prevalence is estimated to be between 0.8 and 8.9 per 100,000 people. This wide range often reflects differences in diagnostic criteria and study populations.

Clinical Statistics and Disease Course

The typical presentation of CIDP accounts for 50% to 60% of all cases, characterized by symmetric motor-predominant weakness and sensory impairment. However, the statistical data on how the disease progresses is vital for patient management:

• Course of Progression: While the disease is generally slowly progressive, approximately one-third (33%) of patients experience a relapsing-remitting course. About 15% of patients face a more steady, relentless progression.
• Symptom Prevalence: Beyond limb weakness, other symptoms are statistically common. Cranial nerve or bulbar involvement (affecting speech, swallowing, or facial movement) is observed in 10% to 20% of cases.
• Histological Hallmarks: On a microscopic level, demyelination and remyelination, the core pathological processes of CIDP, are visualized in 48% to 68% of patients during nerve fiber analysis.

Hospital System Participants: Medical and Pharmacy Directors

For medical and pharmacy directors, this is a familiar tension. IVIG is conceptually generic but expensive in practice, and its administration requires infusion infrastructure, whether in a clinical setting or at home. Vyvgart Hytrulo, as a self-administered subcutaneous injection, offers site-of-care advantages but at a higher per-unit drug cost.

Managed Care and Payers

The managed care and payer stakeholders heavily prioritize the total cost of care, including infusion fees, nursing visits, and pay close attention to the downstream costs of inadequately treated neuropathy.

What Changes

Plans reviewing their CIDP clinical criteria in advance of this evidence should anticipate increased pressure from neuromuscular specialists to remove or narrow the IVIG step requirement, particularly for patients with contraindications, access barriers, or conditions that make repeat infusions clinically impractical.

As we introduce additional therapies to treat CIDP, improvements in clinical-decision making patient care will be appear in several ways:

• Shifting Treatment Trends: The data confirms a clear evolution in care, showing a rising preference for immunoglobulins (43%) over corticosteroids (32%) as a first-line choice in recent years.
• Refining the Definition of Success: By identifying that one-third of patients switch therapies early, the research suggests that refractory status is more common than previously recognized in real-world settings.
• Highlighting Comorbidity Risks: Previous research observed a sharp increase in hypertension (from 27% to 47%) and other issues like back pain and dyslipidemia following treatment initiation. This alerts clinicians to monitor the long-term side effects of standard treatments like corticosteroids more closely.
• A Call for Innovation: The rapid decrease in treatment duration for later lines of therapy underscores that current rescue therapies are often insufficient. Recent research serves as a direct call for the development of safer, more effective therapeutic options for the substantial subset of patients who fail the current standard of care.

By documenting the high frequency of treatment changes and the resulting increase in healthcare use, real-world research provides the evidence needed to advocate for earlier intervention and more personalized treatment strategies for the CIDP community.

New in CIDP Research

Ongoing clinical research continues to transform the landscape for those living with chronic inflammatory demyelinating polyneuropathy (CIDP). Two pivotal Phase 3 studies, EMVIGORATE and EMNERGIZE, are currently evaluating an investigational drug called empasiprubart to address the high unmet needs in this community.

EMVIGORATE: Head-to-Head with Standard of Care

The EMVIGORATE study is designed to compare the efficacy and safety of intravenous empasiprubart directly against the current standard-of-care, intravenous immunoglobulin (IVIg).

• Who it’s for: Adults diagnosed with CIDP.
• Study Design: Participants are randomly assigned to receive either the investigational drug plus a placebo IVIg, or IVIg plus a placebo drug.
• Goal: This “double-dummy” approach ensures that no participant receives only a placebo, allowing researchers to see how empasiprubart performs compared to traditional therapy.

EMNERGIZE: Testing Against Placebo

The EMNERGIZE study evaluates empasiprubart’s efficacy and safety compared to a placebo.

• Who it’s for: Adults with active CIDP who may be treatment-naive or are willing to stop their current medications to try a new approach.
• Study Design: Participants have a 67% chance of receiving the investigational drug in Part A of the trial.
• Goal: To establish a clear baseline of the drug’s effectiveness in stabilizing symptoms and preventing relapses.

Both trials eventually transition all participants to the active investigational drug in “Part B” to monitor long-term safety and benefit. These studies represent a critical step toward providing more targeted, effective options for patients who find current therapies for CIDP insufficient.

References

1. argenx SE. argenx brings neuromuscular leadership to AAN 2026 with new data supporting broader Vyvgart use across MG and CIDP. GlobeNewswire. April 18, 2026. https://www.globenewswire.com/news-release/2026/04/18/3276554/0/en/argenx-Brings-Neuromuscular-Leadership-to-AAN-2026-with-New-Data-Supporting-Broader-VYVGART-Use-Across-MG-and-CIDP.html
2. https://clinicaltrials.gov/study/NCT04281472
3. Hartung HP, Atassi N, Alonso-Alonso M, et al. Characterizing Treatment Patterns and Healthcare Use in Patients and Subgroups with Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A Real-World Study. Neurol Ther. 2026;15(1):269-286. doi:10.1007/s40120-025-00862-3
4. Gogia B, Rocha Cabrero F, Khan Suheb MZ, et al. Chronic Inflammatory Demyelinating Polyradiculoneuropathy. \[Updated 2024 Mar 4\]. In: StatPearls \[Internet\]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK563249/
5. https://clinicaltrials.argenx.com/emvigorate
6. https://clinicaltrials.argenx.com/emnergize