Development

argenx's Vyvgart Hytrulo delivers first Phase III success in IMNM

Efgartigimod alfa and hyaluronidase-qvfc met the primary endpoint of a Phase III trial in autoimmune myositis, delivering the first statistically...

argenx's Vyvgart Hytrulo delivers first Phase III success in IMNM

Netherlands-based argenx SE (Euronext & Nasdaq: ARGX) reported positive Phase III results for efgartigimod alfa and hyaluronidase-qvfc (Vyvgart Hytrulo) in autoimmune myositis, delivering the first statistically significant Phase III evidence of benefit in immune-mediated necrotizing myopathy (IMNM), a subtype with no approved therapy. The ALKIVIA trial showed a 15.4-point greater improvement in mean Total Improvement Score (TIS) at Week 52 versus placebo in the combined IMNM and dermatomyositis (DM) population (47.95 vs 32.56; p=0.0011), with benefits emerging by Week 4 and sustained through a protocol-mandated corticosteroid taper.

The Phase III portion of the seamless Phase II/III study enrolled 175 patients randomized to weekly subcutaneous efgartigimod or placebo on top of existing immunosuppressive therapy. In the prespecified IMNM subgroup, efgartigimod produced a 14.8-point TIS advantage over placebo (p=0.0048). The smaller DM cohort showed a similar 14.5-point numerical benefit but did not reach statistical significance (p=0.1093). All six core measures contributing to TIS favored efgartigimod in both subtypes. No new safety signals were reported.

Efgartigimod blocks the neonatal Fc receptor (FcRn), accelerating the breakdown of IgG antibodies and reducing circulating pathogenic autoantibodies implicated in autoimmune disease. The subcutaneous formulation is already approved as Vyvgart Hytrulo for generalized myasthenia gravis (gMG) and chronic inflammatory demyelinating polyneuropathy (CIDP) in the US.

argenx SE previously reported ALKIVIA+ extension data at EULAR 2026, showing sustained improvement in patients continuing efgartigimod and gains among those switching from placebo following the Phase II portion of the study.

The IMNM result is particularly significant because the disease has no approved therapy, with treatment currently relying on corticosteroids and off-label immunosuppressants. IMNM is associated with autoantibodies including anti-SRP and anti-HMGCR and can cause severe muscle weakness and muscle fiber necrosis.

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The treatment landscape in DM is more developed. Octapharma's Octagam 10% became the first FDA-approved therapy specifically for adult DM in 2021, while Priovant Therapeutics' oral TYK2/JAK1 inhibitor brepocitinib has produced positive Phase III results and is currently under US FDA Priority Review, with a decision expected in Q3 2026. Neither program, however, addresses IMNM.

ALKIVIA therefore gives efgartigimod two potential paths forward: a first approved treatment for IMNM and another therapeutic option in DM if the numerical benefit seen in that smaller subgroup can support regulatory consideration. Detailed results will be presented at an upcoming medical meeting, while argenx has not yet disclosed its regulatory submission plans.


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