Japan's Ministry of Health, Labour and Welfare Grants Regulatory Approval to Efgartigimod for CIDP

Luc Truyen, MD, PhD

(Credit: Argenx)

In recent news, Japan's Ministry of Health, Labour and Welfare (MHLW) has granted regulatory approval to efgartigimod alfa and hyaluronidase-qvfc (Vyvdura; Argenx) as a treatment for adults with chronic inflammatory demyelinating polyneuropathy (CIDP).¹ The agent, a coformulation therapy of ENHANZE (Halozyme Therapeutics), a recombinant human hyaluronidase-based drug delivery technology that enables subcutaneous drug delivery, was previously approved in the U.S. for CIDP in June 2024.

“We had been working intensively with the [Pharmaceuticals and Medical Devices Agency] and [health care professionals] in Japan, so we evidently weren’t surprised by the approval, but it is always rewarding and exciting when patients in a new region are able to access a new innovative treatment like VYVDURA,” Luc Truyen, MD, PhD, chief medical officer at Argenx, told NeurologyLive^®. "The wait is over. Patients around the world had been waiting for decades for a new and innovative mechanism of action to treat CIDP."

The approval in Japan was based on findings from the ADHERE study (NCT04281472), the largest clinical trial of CIDP considered to date, in which treatment with the agent significantly reduced relapse risk compared with placebo. 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 the trial, 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

"First, the mode of action is much more specific than current [standard of care]. [Neonatal Fc receptor] inhibition selectively lowers [immunoglobulin Gs] including auto-antibodies which as our data shows has a significant beneficial effect on clinical outcomes. Second, we can deliver this benefit with an elegant [subcutaneous] formulation enabling self-administration. And as we continue to advance options for patients with a pre-filled syringe, we hope to offer even more convenience with the known safety and efficacy profile of efgartigimod [subcutaneous]," Truyen said to NeurologyLive.

In Stage A of the ADHERE trial, 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: Early Immunotherapy May Be Crucial to Prevent Axonal Damage in CIDP, Study Suggests

Helen Torley, MBChB, MRCP

(Credit: Halozyme)

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.

"We are pleased that VYVDURA, with our innovative ENHANZE drug delivery technology, is now approved for two indications in Japan, enabling greater flexibility and optionality for generalized myasthenia gravis and CIDP patients," Helen Torley, MBChB, MRCP, president and chief executive officer at Halozyme, said in a statement.³ "We look forward to VYVDURA being a new treatment option for an even broader number of patients in Japan."

REFERENCES
1. argenx Announces Approval of VYVDURA (efgartigimod alfa and hyaluronidase-qvfc) in Japan for Adults with Chronic Inflammatory Demyelinating Polyneuropathy. News Release. Published December 27, 2024. Accessed January 27, 2024. https://argenx.com/news/2024/argenx-announces-approval-of-vyvdura--efgartigimod-alfa-and-hyal
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 January 27, 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. Halozyme Announces argenx's VYDURA with ENHANZE® was Granted Regulatory Approval in Japan for Chronic Inflammatory Demyelinating Polyneuropathy. News Release. Halozyme Therapeutics. Published December 30, 2024. Accessed January 17, 2024. https://ir.halozyme.com/news/news-details/2024/Halozyme-Announces-argenxs-VYDURA-with-ENHANZE-was-Granted-Regulatory-Approval-in-Japan-for-Chronic-Inflammatory-Demyelinating-Polyneuropathy/default.aspx