Efgartigimod Meets Primary Endpoint in Phase 3 ALKIVIA Trial of Autoimmune Myositis

Argenx announced positive topline results from the phase 3 portion of ALKIVIA, a study evaluating subcutaneous efgartigimod (VYVGART Hytrulo) in adults with autoimmune myositis. Overall, the trial met its primary endpoint in the combined study population, with a consistent treatment effect observed across both disease subtypes studied.¹

"For decades, people living with autoimmune myositis have relied on corticosteroids and broad immunosuppression, and those with IMNM have had no approved option at all. These are the first Phase 3 results to show that precision targeting of FcRn with efgartigimod can deliver meaningful benefit in this disease," Luc Truyen, MD, PhD, chief medical officer at argenx, said in a statement.¹

Phase 3 results

In the combined population of IMNM and dermatomyositis (DM) patients, efgartigimod produced a statistically significant, 15.4-point greater improvement in mean Total Improvement Score (TIS), the primary end point, at week 52 compared with placebo (47.95 vs 32.56; P = .0011). Improvement over placebo began as early as week 4 and remained statistically significant through the full year of treatment, despite a concurrent, protocol-mandated corticosteroid taper.¹

In the prespecified IMNM subgroup, the primary endpoint was also met, with a 14.8-point greater improvement in mean TIS over placebo (45.05 vs 30.24; P = .0048).

In the smaller DM subgroup, a similarly sized improvement of 14.5 points was observed (51.51 vs 36.96), though it did not reach statistical significance (P = .1093). Across both subtypes, all 6 core TIS component measures favored efgartigimod, spanning muscle strength, physical function, and disease activity beyond the muscle; skin disease activity also improved in the DM group.

The safety profile was described as consistent with efgartigimod's established profile, and no new safety signals were reported.

Rohit Aggarwal, MD, MS, professor of medicine and co-director of the Myositis Center at the University of Pittsburgh and an ALKIVIA investigator, called immune-mediated necrotizing myopathy (IMNM) “the most refractory form of this disease." He noted that many patients carry irreversible muscle damage, making meaningful improvement difficult to achieve, which he said made the trial's results "compelling and groundbreaking.”¹

Study design

For context, ALKIVIA is a global, randomized, double-blind, placebo-controlled, multicenter, operationally seamless phase 2/3 study evaluating weekly subcutaneous efgartigimod injections against placebo in patients with active autoimmune myositis on background standard-of-care therapy. The study enrolled 264 patients across North America, Europe, the Middle East, and Asia-Pacific, including China and Japan.^1,2

The trial was conducted in 2 stages under a single protocol. An initial phase 2 portion was analyzed after the first 89 patients completed 24 weeks of treatment. The phase 3 portion then enrolled an additional 175 patients and incorporated the corticosteroid taper referenced above.

The phase 3 primary endpoint was mean TIS, a composite measure combining physician and patient global disease activity assessments, manual muscle testing, a disability index, muscle enzyme levels, and extramuscular disease activity, assessed at 52 weeks. In addition, prespecified analyses evaluated the combined IMNM/DM population and each subtype individually.

How we got here

Efgartigimod first reached the market in December 2021, when the FDA approved an intravenous formulation for AChR antibody-positive generalized myasthenia gravis (gMG).³ A subcutaneous formulation, VYVGART Hytrulo, followed for gMG in June 2023, and the drug became the first FcRn blocker approved for chronic inflammatory demyelinating polyneuropathy (CIDP) in June 2024.^4,5 It's also approved for immune thrombocytopenia in Japan.

More recently, the phase 3 ADAPT SERON trial met its primary endpoint in seronegative gMG in August 2025, and argenx has said it plans to seek a label expansion covering that population.⁶ Prior to the newly announced data, the earlier phase 2 portion of ALKIVIA had already shown a significant benefit: at the 2025 AANEM meeting, researchers reported a 24-week mean TIS of 50.45 with efgartigimod versus 35.65 with placebo (P = .0004) in the trial's first 89 patients, along with faster time to clinical improvement and fewer severe adverse events than placebo.²

Mechanism and disease background

Efgartigimod is a first-in-class human IgG1 antibody fragment that blocks the neonatal Fc receptor (FcRn) to reduce circulating IgG autoantibodies, which are increasingly understood to drive muscle fiber damage and extramuscular manifestations across autoimmune myositis subtypes.

Roughly 100,000 people in the US live with autoimmune myositis, including an estimated 20,000 with IMNM and 40,000 with DM.¹ Up to 80% report long-term disability despite treatment with corticosteroids and broad immunosuppressants, which carry substantial cumulative toxicity.¹

Detailed results from ALKIVIA are expected to be presented at an upcoming medical meeting. argenx said efgartigimod also continues to be evaluated in other autoimmune rheumatologic diseases, including Sjögren's disease and systemic sclerosis.

REFERENCES
1. argenx Announces Positive Topline Results from Phase 3 ALKIVIA Trial of Efgartigimod in Autoimmune Myositis. News release. argenx SE. August 17, 2026. Accessed August 17, 2026. https://argenx.com/news/2026/press-release-3345813
2. Aggarwal R, Rodriguez Garcia SC, Neto A, et al. Efficacy and Safety of Subcutaneous Efgartigimod in Adult Participants With Active Idiopathic Inflammatory Myopathy: Phase 2 Results From the ALKIVIA Study. Presented at: 2025 AANEM; October 29 to November 1, 2025; San Francisco, CA. Abstract 218.
3. Vyvgart (efgartigimod alfa-fcab) FDA Approval History. Drugs.com. Accessed August 17, 2026. https://www.drugs.com/history/vyvgart.html
4. argenx SE. Form 6-K, First Quarter 2024 Financial Results and Business Update. US Securities and Exchange Commission. April 30, 2024. Accessed August 17, 2026. https://www.sec.gov/Archives/edgar/data/1697862/000110465924036881/tm248913d1_ex99-1.htm
5. FDA Approves Efgartigimod Alfa and Hyaluronidase for CIDP. AJMC. June 2024. Accessed August 17, 2026. https://www.ajmc.com/view/fda-approves-efgartigimod-alfa-and-hyaluronidase-for-cidp
6. argenx to Highlight Key Data and Breadth of Immunology Innovation at 2025 AANEM Annual Meeting and MGFA Scientific Session. News release. argenx. October 15, 2025. Accessed August 17, 2026. https://argenx.com/news/2025/press-release-3166778