Newly Unveiled EPIC Trial Pins Myasthenia Gravis Medications Nipocalimab Against Efgartigimod for Efficacy

A new phase 3, head-to-head trial testing two FDA-approved medications for myasthenia gravis (gMG) was unveiled this week at the 2025 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting, held October 29 to November 1, in San Francisco, California. The study, dubbed EPIC, addressed whether nipocalimab (Amaavy; Johnson & Johnson) provides superior efficacy to efgartigimod (Vyvgart; argenx) in the latter part of efgartigimod treatment cycles.^1,2

EPIC, considered the first randomized trial testing advanced therapeutics in patients with gMG, will include 80 FcRn-naïve adult participants who have a Myasthenia Gravis-Activites of Daily Living (MG-ADL) score of greater than or equal to 5. In the trial, patients are randomized 1:1 to either nipocalimab every 2 weeks for 12 weeks (arm 1) or efgartigimod weekly at 10 mg/kg for 4 weeks (arm 2).

The study also features an experimental, switching arm, where participants previously treated with efgartigimod in arm 2, as well as those with at least 1 on-label efgartigimod cycle, can crossover to nipocalimab, where they are treated for 12 weeks. This cohort, considered arm 3, excludes those who have a current or recent malignancy, a thymectomry within the past year, or any confirmed, suspected, or familial immunodeficiency unrelated to gMG treatment.

"The EPIC study marks an important step forward in advancing care for people living with gMG," Leonard L. Dragone, MD, PhD, disease area leader, Autoantibody and Rheumatology, Johnson & Johnson Innovative Medicine, said in a statement.¹ "By directly comparing IMAAVY to another FcRn blocker and incorporating a treatment-switch arm, EPIC will provide critical insights into how physicians can best start and transition gMG patients within this class. These findings will help guide real-world clinical decisions and strengthen confidence in the most effective treatment strategies."

Efgartigimod, an engineered Fc fragment that binds FcRn, was approved for adults with AChR-antibody-positive gMG in in December 2021 in an intravenous formulation, and later expanded to subcutaneous forms in 2023. Nipocalimab, a fully human anti-FcRn monoclonal antibody, is an intravenously administered treatment that gained FDA approval in April 2025 for gMG in adults and adolescents who are AChR- or MuSK-positive. The administration of nipocalimab includes an initial 30 mg/kg IV dose, followed by a 15 mg/kg dosing regimen every 2 weeks.

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The primary outcome measure for EPIC is the averaged mean percent change from baseline in total immunoglobulin (IgG) levels over weeks 8, 10, and 12. Other secondary outcomes include change in MG-ADL scores, Quantitative Myasthenia Gravis (QMG) total scores, and safety, demonstrated through adverse events (AEs), serious AEs, and AEs of special interest.³

A recently presented indirect treatment comparison study of the Vivacity-MG3 trial (NCT), the study that led to nipocalimab’s approval, showed that the medication outperforms other approved FcRn blockers in the treatment of gMG. In the data, revealed at the 2025 European Academy of Neurology Congress, nipocalimab displayed comparable onset of symptom relief at 1-week and greater or statistically significant improvement in MG-ADL scores when compared with published phase 3 data of other marketed FcRn blockers at different time points up to 24 weeks.⁴

In unanchored population-adjusted indirect comparison, researchers reported that nipocalimab versus 1 treatment revealed a mean MG-ADL score difference of -2.36 (95% CI, -3.56 to -1.16; P = .001] at 8 weeks, which continued trending up to 24 weeks (P <.05). For another comparator, results at 10 weeks showed that nipocalimab displayed a mean difference of -2.38 at 7mg/kg (95% CI, -3.57 to -1.18; P <.001) and a mean difference of -3.14 with 10mg/kg (95% CI, 4.15 to -2.14; P <.001), continuing this trend up to 14 weeks (P <.001).

Click here for more AANEM 2025 coverage.

REFERENCES
1. Muppidi S, Corse A, Wiendl H, et al. EFFICACY AND SAFETY OF NIPOCALIMAB VS EFGARTIGIMOD IN A RANDOMIZED, OPEN-LABEL, PHASE 3B, INTERVENTIONAL TRIAL INCLUDING WITHIN CLASS SWITCHING FROM EFGARTIGIMOD TO NIPOCALIMAB (EPIC): STUDY DESIGN. Presented at: 2025 AANEM Annual Meeting; October 29-Nov 1; San Francisco, California. Abstract 170
2. Johnson & Johnson announces first head-to-head study comparing IMAAVY™ with an alternative FcRn blocker in generalized myasthenia gravis (gMG) at AANEM Annual Meeting. News release. Johnson & Johnson. October 29, 2025. Accessed October 30, 2025. https://www.prnewswire.com/news-releases/johnson--johnson-announces-first-head-to-head-study-comparing-imaavy-with-an-alternative-fcrn-blocker-in-generalized-myasthenia-gravis-gmg-at-aanem-annual-meeting-302597514.html
3. Comparative Efficacy of Nipocalimab and Efgartigimod in Participants With Generalized Myasthenia Gravis (EPIC). Clinicaltrial.gov. Updated October 16, 2025. Accessed October 30, 2025. https://clinicaltrials.gov/study/NCT07217587
4. Jacob S, et al. Comparative Efficacy of Nipocalimab and Other FcRn Blocker Therapies in Generalized Myasthenia Gravis. Oral ePresentation at 11th European Academy of Neurology (EAN) Congress. EPR-301