FDA Approves Efgartigimod as New Treatment for Chronic Inflammatory Demyelinating Polyneuropathy

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The therapy is the first and only neonatal Fc receptor blocker approved for the treatment of CIDP, and will be available as a once-weekly, 30- to 90-second subcutaneous injection.

Luc Truyen MD, PhD

Luc Truyen MD, PhD

The FDA has approved Argenx's coformulation therapy efgartigimod alfa and hyaluronidase-qvfc (Vyvgart Hytrulo) as a new treatment for adults with chronic inflammatory demyelinating polyneuropathy (CIDP). The therapy is the first and only neonatal Fc receptor (FcRn) blocker approved for the treatment of CIDP, and will be available as a once-weekly, 30- to 90-second subcutaneous injection.1

“Argenx continues to pursue our ambition to turn science into solutions for patients with severe autoimmunity,” Luc Truyen MD, PhD, the chief medical officer of argenx, said in a statement.1 “Patients have been waiting, and today, argenx is delivering the first innovative treatment for CIDP in more than 30 years. Vyvgart Hytrulo is a precision tool that has been shown to drive meaningful benefits for patients. Today’s FDA approval means that CIDP patients have a transformational new treatment option and further affirms the therapeutic profile of Vyvgart Hytrulo and the potential of FcRn blockade in IgG-mediated autoimmune diseases.”

The therapy was approved based on data from the pivotal phase 3 ADHERE study (NCT04281472) in which treatment with the agent significantly reduced relapse risk compared with placebo. All told, patients treated with Vyvgart Hytrulo had a 61% attenuated risk relative to placebo (P = .00039), with a safety profile that was consistent with previous studies.2

CIDP is an acquired immune-mediated inflammatory disorder of the peripheral nervous system. Currently, it is mainly managed through corticosteroids, intravenous immunoglobulins, plasma exchange, and chronic immunosuppressive agents, either alone or in combination. 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.

“Today marks a groundbreaking day for the treatment of CIDP. Existing treatments have been limited to corticosteroids and plasma-derived therapies. These treatments, while effective for many patients, can be challenging for some patients to receive,” Jeffrey Allen, MD, a professor in the department of neurology at the University of Minnesota and principal investigator in the ADHERE trial, said in a statement.1 “Today’s approval of Vyvgart Hytrulo gives doctors and patients a new, safe, and effective treatment option that may lessen the burden of treatment that some patients experience.”

Considered the largest clinical trial of CIDP to date, ADHERE 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 Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score, the Inflammatory Rasch-built Overall Disability Scale I (I-RODS) or grip strength. 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 INCAT deterioration.

READ MORE: Combination Therapy of Corticosteroids and Immunosuppressants Shows Efficacy in Rare Case of Overlapping CIDP and NMOSD

The study, which consisted of patients who were either treatment-naïve or on IgG therapy or corticosteroids, showed consistent response rates with Vyvgart Hytrulo across CIDP medication subgroups. In Stage A, 70% (214 of 304) of patients 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. The rates of ECI were increased to 78% (214 of 275) during a sensitivity analysis that included those who received at least 4 injections to reach the full IgG-lowering effect.

Following Stage A, 221 responders proceeded to Stage B, where the primary end point was the relative risk of relapse based on time to relapse on the INCAT Disability Score. Not only was the primary end point met, but the study revealed that patients on active treatment had a low relapse rate than placebo at week 24 (26% vs 54%) and week 48 (34% vs 60%). In addition, 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.

Efgartigimod, a human IgG1 anitbody Fc-fragment, blocks the FcRn receptor and reduces IgG autoantibody levels in the body. It was approved as a medication for patients with generalized myasthenia gravis (gMG) in 2021 based on data from the phase 3 ADAPT trial (NCT03669588).3 In the original analysis, the agent was shown to be well-tolerated and efficacious, meeting its primary end point of improvement in Myasthenia Gravis–Activities of Daily Living (MG-ADL) item scores relative with the placebo (67.7% vs 29.7%; P <.0001). Additionally, 40.0% of efgartigimod-treated patients who were anti-acetylcholine receptor (AChR) antibody-positive achieved minimal or no symptoms compared with 11.1% treated with placebo.4

At the 2023 American Association of Neuromuscular & Electrodiagnostic Medicine Annual Meeting, an analysis studied the therapy’s safety across trials of gMG, pemphigus, and immune thrombocytopenia, all conditions for which efgartigimod was approved for. Led by Kelly Gwathmey, MD, results showed that efgartigimod had a consistent safety profile, with treatment-emergent adverse events (TEAEs) that were comparable with placebo and mild to moderate in severity.

In the phase 3 ADAPT trial (NCT03669588), 77.4% of efgartigimod-treated patients reported TEAEs vs 84.3% in the placebo group. In the phase 3 ADVANCE trial (NCT04188379), 93.0% reported TEAEs when treated with efgartigimod vs 95.6% of those on placebo. Lastly, 85% efgartigimod-treated patients reported TEAEs in a phase 2 pemphigus trial (NCT03334058). Discontinuation rates because of AEs remained low in efgartigimod-treated groups, with just 3.6%, 3.5%, and 3.0% of patients discontinuing across ADAPT, ADVANCE, and the study of pemphigus.5

REFERENCES
1. argenx Announces FDA Approval of VYVGART Hytrulo for Chronic Inflammatory Demyelinating Polyneuropathy. News release. Argenx. June 21, 2024. Accessed June 21, 2024. https://www.us.argenx.com/news/argenx-announces-fda-approval-vyvgart-hytrulo-chronic-inflammatory-demyelinating-polyneuropathy
2. 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 July 19, 2024. 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
3. FDA Approves New Treatment for Myasthenia Gravis. News release. FDA. December 17, 2021. Accessed July 21, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-myasthenia-gravis
4. Argenx Announces Positive Topline Phase 3 Data From ADAPT-SC Study Evaluating Subcutaneous Efgartigimod for Generalized Myasthenia Gravis. News release. March 22, 2022. Accessed July 21, 2024. https://www.argenx.com/news/argenx-announces-positive-topline-phase-3-data-adapt-sc-study-evaluating-subcutaneous
5. Gwathmey K, Goebeler M, Broome CA, et al. Overview of the Safety Profile from Efgartigimod Clinical Trials in Participants With Diverse Immunoglobulin G-Mediated Autoimmune Diseases. Presented at: American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting; November 1-4, 2023; Phoenix, AZ. Abstract 44.
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