Assessing Efgartigimod for Acute Neuromyelitis Optica Spectrum Disorder: The Phase 2 FACT Trial

Welcome to NeurologyLive's Clinical Trial in Focus. Every month, an ongoing clinical trial in the landscape of neurology is featured, highlighting the design of the study, the targeted patient population, the enrollment criteria, the primary and secondary end points, and its potential implications for clinical care. This month’s spotlight is the phase 2 FACT trial (NCT06497374), which aims to assess the therapeutic potential of efgartigimod (Vyvgart; argenx), a human IgG1 antibody fragment therapy, in patients living with neuromyelitis optica spectrum disorder (NMOSD).

Efgartigimod

Efgartigimod is designed to block the neonatal Fc receptor, leading to reduction of circulating pathogenic immunoglobulin G antibodies implicated in several autoimmune neurologic disorders. Reflecting its broad therapeutic potential, the therapy has previously received multiple FDA approvals across neuromuscular diseases. In December 2021, the FDA approved efgartigimod for adults with anti–acetylcholine receptor (AChR) antibody–positive generalized myasthenia gravis (gMG), and more recently expanded the indication to include adults with AChR antibody–seronegative gMG.^1,2 In June 2024, the agency approved the coformulation therapy efgartigimod alfa and hyaluronidase-qvfc (Vyvgart Hytrulo) for the treatment of adults with chronic inflammatory demyelinating polyneuropathy.³

Phase 2 FACT Trial

The ongoing phase 2 randomized controlled FACT trial evaluates the efficacy and safety of efgartigimod alfa in patients with anti–aquaporin-4 antibody-positive NMOSD during acute attacks. Sponsored by Tianjin Medical University General Hospital and led by Fu-Dong Shi, MD, PhD, a professor of neurology at Beijing Tiantan Hospital, the study looks at whether efgartigimod, an IgG1 Fc fragment designed to compete with IgG for FcRn binding and reduce circulating IgG levels, may have therapeutic potential in acute NMOSD management.

Inclusion Criteria

Eligible participants are men or women aged 18 to 75 years who meet the 2015 International Panel for Neuromyelitis Optica Diagnosis criteria for NMOSD. To be included, participants must have an acute Expanded Disability Status Scale (EDSS) nadir between 2.5 and 7.5, with a documented increase of at least 0.5 points from baseline attributable to an acute relapse.

All participants are required to have serum aquaporin-4 immunoglobulin G (AQP4-IgG) positivity confirmed by cell-based assay. Enrollment requires confirmation of an acute NMOSD attack, defined as new or worsening optic neuritis and/or myelitis with associated clinical worsening, an increase in EDSS score, and symptom duration greater than 24 hours occurring more than 1 month after the prior relapse. Relapse is confirmed using both clinical assessment and imaging, with pseudorelapse excluded.

To be eligible, patients’ MRI must demonstrate new or enhancing lesions consistent with acute inflammatory activity. Participants receiving immunosuppressive therapy prior to screening must agree to discontinue such treatment. Background disease-modifying treatment is required to be stable for at least 3 months prior to enrollment.

Exclusion Criteria

Individuals are excluded if they present with clinical manifestations of NMOSD other than optic neuritis or myelitis. Patients experiencing a severe NMOSD attack, as determined by the investigator and defined as requiring assisted ventilation or being at high risk of requiring assisted ventilation during the study, are excluded. Individuals with total immunoglobulin G (IgG) levels ≤6 g/L at screening or a B-cell count ≤5% of the lower limit of normal at screening are not eligible for participation.

Patients who have received high-dose intravenous methylprednisolone in 4 weeks prior to screening are excluded, as are those who have received intravenous immunoglobulin, plasma exchange, or immunoadsorption in the same 4-week period. Receipt of any vaccination in 4 weeks prior to screening or planned vaccination during the study period is also an exclusion criterion.

Individuals who have received monoclonal antibodies or other investigational agents with immunomodulatory effects in 3 months or 5 half-lives (whichever is longer) prior to screening are excluded. Patients with known hypersensitivity to any component of the study drug, other FcRn-targeting agents, or MRI contrast media are not eligible.

Participants with contraindications to methylprednisolone are excluded. Individuals with clinically significant active infections, including unresolved or inadequately treated infections such as active tuberculosis, are not eligible for enrollment. Patients with positive screening results for hepatitis B or hepatitis C who have received live or live-attenuated vaccines within 6 weeks prior to baseline are excluded.

Individuals who are unable to undergo MRI are not eligible. Patients with other ophthalmic conditions that may affect visual function, as determined by the investigator, are also excluded.

Efgartigimod+IVMP Group

Patients receive intravenous efgartigimod alfa at a dose of 10 mg/kg per infusion, administered over approximately 2 hours at weeks 0, 1, 2, and 3. Efgartigimod is administered no later than 2 days after initiation of high-dose IV methylprednisolone. IV methylprednisolone is given at 1,000 mg/day for 5 consecutive days, followed by 500 mg/day for 3 days, 240 mg/day for 3 days, and 120 mg/day for 3 days.

Following IV therapy, patients transition to an oral prednisone taper beginning at 60 mg daily for 7 days, then 50 mg daily for 7 days, and 40 mg daily for 7 days, with subsequent dose reductions of 5 mg every 2 weeks until a maintenance dose of 10 mg is reached. After week 4, inebilizumab is initiated per approved indication for relapse prevention.

IVMP Group

Patients in this intervention group receive injectable methylprednisolone sodium succinate as described in Arm A. After Week 4, inebilizumab is introduced in accordance with its approved indication for relapse prevention.

Efgartigimod Group

Patients receive efgartigimod alfa administered as an intravenous infusion at a dose of 10 mg/kg, with each infusion lasting approximately 2 hours, at Weeks 0, 1, 2, and 3. Beginning at Week 4, inebilizumab is initiated per indication for relapse prevention.

Primary and Secondary Outcomes

The study evaluates change in neurological disability as measured by the Expanded Disability Status Scale (EDSS) as the primary outcome. Secondary outcomes include changes in Functional System (FS) scores and Medical Research Council (MRC) scores at weeks 4, 12, and 24, as well as changes in EDSS, FS, and MRC scores across these time points. Additional secondary endpoints assess health-related quality of life using the EQ-5D-5L, changes in high-contrast visual acuity among participants with acute optic neuritis, and changes in optical coherence tomography parameters in those with optic neuritis.

The study also evaluates the proportion of participants requiring rescue therapy during the study period, along with safety outcomes including the incidence of adverse events, vital signs, clinical laboratory parameters, and electrocardiogram findings. Exploratory outcomes include changes in serum total IgG levels, AQP4-IgG antibody titers, glial fibrillary acidic protein, and neurofilament light chain, as well as changes in MRI lesion size and extent.

Prior Research

Previous research evaluating efgartigimod in NMOSD has primarily focused on its ability to reduce pathogenic immunoglobulin G autoantibodies through neonatal Fc receptor inhibition. In a recently published retrospective study, investigators assessed efgartigimod in combination with IVMP during acute NMOSD attacks and reported reductions in EDSS scores compared with IVMP alone, with the combination therapy demonstrating a generally acceptable safety profile. The analysis included 11 patients, of whom 4 received efgartigimod plus IVMP and 7 received IVMP alone. Authors noted that the findings were preliminary and limited by the small sample size and retrospective design.²

Click here to view more Clinical Trial in Focus.

REFERENCES
1. FDA Approves New Treatment for Myasthenia Gravis. News release. FDA. December 17, 2021. Accessed May 22, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-myasthenia-gravis
2. Argenx Announces U.S. FDA Approval Expanding VYVGART and VYVGART Hytrulo for Use in All Adult Patients Living with gMG. Argenx. News Release. May 22, 2026. Accessed: May 8, 2026. https://argenx.com/news/2026/press-release-3291372
3. argenx Announces FDA Approval of VYVGART Hytrulo for Chronic Inflammatory Demyelinating Polyneuropathy. News release. Argenx. June 21, 2024. Accessed JMay 22, 2026. https://www.us.argenx.com/news/argenx-announces-fda-approval-vyvgart-hytrulo-chronic-inflammatory-demyelinating-polyneuropathy
4. Yang W, Chen P, Guo J, Feng H, Huang X. Clinical efficacy of efgartigimod combined with intravenous methylprednisolone in the acute phase of neuromyelitis optica spectrum disorders. Orphanet J Rare Dis. 2024;19(1):483. Published 2024 Dec 21. doi:10.1186/s13023-024-03501-6