argenx Submits Biologics License Application to U.S. Food and Drug Administration for Subcutaneous Efgartigimod for Treatment of Generalized Myasthenia Gravis

Submission package based on positive data from the Phase 3 ADAPT-SC trial demonstrating noninferiority of subcutaneous (SC) efgartigimod compared to intravenously administered VYVGART® (efgartigimod alfa-fcab) based on total immunoglobulin G (IgG) reduction at day 29

AMSTERDAM, The Netherlands I September 21, 2022 I argenx SE (Euronext & Nasdaq: ARGX), a global immunology company committed to improving the lives of people suffering from severe autoimmune diseases, today announced the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for SC efgartigimod (1000mg efgartigimod-PH20) for the treatment of generalized myasthenia gravis (gMG) in adult patients.

SC efgartigimod is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE® drug delivery technology. ENHANZE facilitates the subcutaneous injection delivery of biologics that are typically administered via intravenous (IV) infusion.

“Our vision for the gMG program is to deliver the broadest treatment offering for people living with this debilitating, and often overlooked disease. Every individual experiences gMG differently, which is why we’re excited about the possibility of introducing multiple ways to meet the needs of patients, including with route of administration and dosing schedule,” said Tim Van Hauwermeiren, Chief Executive Officer of argenx. “The submission of this BLA is the latest milestone in honoring our commitment to the gMG patient community. We look forward to working closely with the agency through the BLA review process and to potentially bringing forth another first-in-class option for gMG patients.”

The BLA submission package includes data from the Phase 3 ADAPT-SC study evaluating the noninferiority of the pharmacodynamic (PD) effect of SC efgartigimod as compared with intravenously administered VYVGART in adult patients with gMG. The majority of enrolled patients were positive for acetylcholine receptor (AChR) antibodies, but the trial also included patients where AChR antibodies were not detected.

ADAPT-SC met its primary endpoint (p< 0.0001) of total IgG reduction from baseline at day 29 demonstrating noninferiority of SC efgartigimod to VYVGART. Patients treated with SC efgartigimod achieved mean total IgG reduction of 66.4% from baseline at day 29, compared to 62.2% reduction with VYVGART. Results were consistent across the overall population, including those with AChR antibodies and patients where AChR antibodies were not detected. Further, 69.1% of patients treated with SC efgartigimod were responders on the Myasthenia Gravis Activities of Daily Living (MG-ADL) score. Responders are defined as having at least a two-point improvement on the MG-ADL score for at least four consecutive weeks. 65.5% of patients treated with SC efgartigimod were responders on the Quantitative Myasthenia Gravis (QMG) score. Responders are defined as having at least a three-point improvement on the QMG score for at least four consecutive weeks. Minimal symptom expression (MSE), a measure of symptom-free status, was achieved in 37% of SC efgartigimod-treated patients after one treatment cycle. Onset of effect was also consistent with the Phase 3 ADAPT study.

The safety profile for SC efgartigimod was consistent with the ADAPT study. It was generally well-tolerated; the most frequent adverse event being injection site reactions (ISRs), commonly observed with biologics administered subcutaneously. All ISRs were mild to moderate and resolved over time. After completing ADAPT-SC, 95% of participants entered ADAPT-SC+, a three-year open-label extension study evaluating the long-term safety and tolerability of SC efgartigimod.

Phase 3 ADAPT-SC Trial Design

The Phase 3 ADAPT-SC trial was a multicenter, randomized, open-label, parallel-group study evaluating the noninferiority of the pharmacodynamic (PD) effect of SC efgartigimod (1000mg efgartigimod-PH20) as compared with VYVGART (10mg/kg) in patients with gMG. The pharmacodynamic effect as measured by percent change from baseline in total IgG levels at day 29, one week after the last dose of IV or SC efgartigimod, served as the primary endpoint in the ADAPT-SC trial. The correlation between total IgG reduction and clinical benefit in gMG was demonstrated in a Phase 2 trial and the Phase 3 ADAPT trial, which served as the basis for approval of VYVGART in the U.S., Japan and Europe. Safety, clinical efficacy, immunogenicity and pharmacokinetics (PK) were also assessed.

A total of 110 adult patients with gMG in North America, Europe and Japan enrolled in the ADAPT-SC trial and were treated. Inclusion criteria of the trial were the same as the Phase 3 ADAPT trial of VYVGART; enrolled patients had a confirmed gMG diagnosis and an MG-ADL total score of at least 5 with greater than 50% of the total score attributed to non-ocular symptoms, at screening and baseline. Patients were on a stable dose of at least one gMG treatment prior to randomization, including acetylcholinesterase inhibitors, corticosteroids or nonsteroidal immunosuppressive drugs, and were required to remain on that stable dose throughout the primary trial. Patients were eligible to enroll in ADAPT-SC regardless of antibody status, including patients with AChR antibodies (AChR-Ab+) and patients where AChR antibodies were not detected.

Patients were randomized in a 1:1 ratio to receive SC efgartigimod or IV efgartigimod for one treatment cycle consisting of four doses at weekly intervals. The total study duration was approximately 12 weeks, including seven weeks of follow-up after the treatment cycle.

See the full Prescribing Information for VYVGART in the U.S., which includes the below Important Safety Information. For more information related to VYVGART in Japan, visit argenx.jp.

IMPORTANT SAFETY INFORMATION FOR VYVGART® (efgartigimod alfa-fcab) intravenous (IV) formulation (U.S. PRESCRIBING INFORMATION)

What is VYVGART® (efgartigimod alfa-fcab)?
VYVGART is a prescription medicine used to treat a condition called generalized myasthenia gravis, which causes muscles to tire and weaken easily throughout the body, in adults who are positive for antibodies directed toward a protein called acetylcholine receptor (anti-AChR antibody positive).

About Efgartigimod
Efgartigimod is an antibody fragment designed to reduce pathogenic immunoglobulin G (IgG) antibodies by binding to the neonatal Fc receptor and blocking the IgG recycling process. Efgartigimod is being investigated in several autoimmune diseases known to be mediated by disease-causing IgG antibodies, including neuromuscular disorders, blood disorders, and skin blistering diseases, in both an intravenous and subcutaneous (SC) formulation. SC efgartigimod is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE® drug delivery technology.

About VYVGART

VYVGART® (efgartigimod alfa-fcab) is a human IgG1 antibody fragment that binds to the neonatal Fc receptor (FcRn), resulting in the reduction of circulating immunoglobulin G (IgG) autoantibodies. It is the first and only approved FcRn blocker. VYVGART is approved in the United States and Europe for the treatment of adults with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody positive, and in Japan for the treatment of adults with gMG who do not have sufficient response to steroids or non-steroidal immunosuppressive therapies (ISTs).

About Generalized Myasthenia Gravis

Generalized myasthenia gravis (gMG) is a rare and chronic autoimmune disease where IgG autoantibodies disrupt communication between nerves and muscles, causing debilitating and potentially life-threatening muscle weakness. Approximately 85% of people with MG progress to gMG within 24 months1, where muscles throughout the body may be affected. Patients with confirmed AChR antibodies account for approximately 85% of the total gMG population1.

About argenx

argenx is a global immunology company committed to improving the lives of people suffering from severe autoimmune diseases. Partnering with leading academic researchers through its Immunology Innovation Program (IIP), argenx aims to translate immunology breakthroughs into a world-class portfolio of novel antibody-based medicines. argenx developed and is commercializing the first-and-only approved neonatal Fc receptor (FcRn) blocker in the U.S., Japan and the EU. The Company is evaluating efgartigimod in multiple serious autoimmune diseases and advancing several earlier stage experimental medicines within its therapeutic franchises. For more information, visit www.argenx.com and follow us on LinkedInTwitter, and Instagram

1 Behin et al. New Pathways and Therapeutics Targets in Autoimmune Myasthenia Gravis. J Neuromusc Dis 5. 2018. 265-277

SOURCE: argenx

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