Argenx shares fall about 13% after it stops a Phase 3 Vyvgart trial in Sjögren's disease

Argenx said Thursday it is stopping a late-stage trial of its flagship drug, Vyvgart, in Sjögren's disease after an interim look at the data showed the study could not succeed. The decision closes off, for now, one of the main routes the company had mapped for taking the medicine beyond its approved uses, mostly nerve and muscle disorders, and into rheumatology.

The Phase 3 study, called UNITY, was comparing weekly injections of efgartigimod, the antibody in Vyvgart, given under the skin, with a placebo in adults with moderate-to-severe Sjögren's disease. An independent data monitoring committee reviewed an interim analysis and recommended ending the study for futility, concluding it was unable to meet its main goal: a reduction in systemic disease activity, measured on a standard clinical scale, after 48 weeks. Safety was in line with the drug's established profile, and no new safety signals were found, the company said. Argenx had expected the results in the second half of 2027.

The company did not publish any efficacy figures from the interim look, so it is not yet clear how far the drug fell short. It said it would analyze the full data set once the study is closed and its database locked, and share what it learns.

"We are disappointed by this outcome, most of all for people living with Sjögren's disease, who are still waiting for treatments that fundamentally change the course of their disease," said Luc Truyen, the chief medical officer. He called Sjögren's "one of the most heterogeneous and complicated diseases in immunology."

Why Sjögren's mattered for Vyvgart

Sjögren's is a chronic autoimmune disease in which the immune system attacks the glands that make tears and saliva. Patients commonly live with dry eyes and mouth, fatigue and joint pain, and in a substantial share of them the disease reaches other organs. It affects about nine women for every man. No approved medicine treats the underlying disease rather than its symptoms, which is why the study had been watched as a large opening for Vyvgart.

Vyvgart works by blocking a receptor called FcRn, which lowers the level of the antibodies that drive several autoimmune diseases. It is approved for generalized myasthenia gravis, a muscle-weakness disorder; its under-the-skin version, Vyvgart Hytrulo, is also approved for chronic inflammatory demyelinating polyneuropathy, a nerve disease; and in Japan the drug is approved for immune thrombocytopenia. Sales are growing fast. Global product net sales reached $1.5 billion in the second quarter, up 60% from a year earlier, and the company has set a goal of 10 labeled indications and 50,000 patients treated by 2030.

Rheumatology was meant to be the next leg of that growth. In August, Vyvgart Hytrulo met the main goal of the Phase 3 ALKIVIA trial in autoimmune myositis, an inflammatory muscle disease, with patients on the drug improving 15.4 points more than those on placebo on a combined score after a year. Argenx had described that readout as a key milestone for expanding into rheumatology, and at the time it named Sjögren's and systemic sclerosis as other rheumatologic diseases where it was testing the drug.

Sjögren's has been a hard target. Analysts at Bernstein wrote that its varied presentation makes it particularly difficult to choose the right patients for trials, and that before Novartis reported positive results for its drug candidate ianalumab last year, there had been no meaningful innovation in the disease for more than two decades.

A positive result in celiac disease

Argenx paired the news with a positive mid-stage result for FB102, an antibody it gained through its acquisition of Forte Biosciences, a deal valued at about $2.2 billion that it completed in August. In a Phase 2 trial of 126 adults with celiac disease who were put through an eight-week gluten challenge, FB102 met its main goal, protecting the lining of the small intestine better than placebo on a measure of tissue damage at day 78, with a p-value of 0.0176. Symptom and inflammation measures pointed the same way, and no new safety signals emerged. FB102 works differently from Vyvgart, blocking CD122, part of the signaling that activates disease-driving immune cells.

There are no approved medicines for celiac disease; patients manage it with a strict gluten-free diet. Argenx said it plans to move FB102 into Phase 3 and is also testing it in vitiligo and alopecia areata. Detailed results are due at a medical meeting.

What is still running

Thursday's decision covered only the Sjögren's study and does not affect Vyvgart's approved uses. In July, Argenx said a registrational study in primary immune thrombocytopenia, an autoimmune bleeding disorder, would report in the first half of 2027, that a registrational study in Graves' disease was under way, and that it planned to expand into ocular myasthenia gravis. It also said then that its second late-stage drug, empasiprubart, would report registrational results in multifocal motor neuropathy, a rare nerve disease, in the fourth quarter.

How the shares are trading

Argenx shares were down 12.7% at €732.00 on Euronext Brussels at 3:27 p.m. local time, from €838.60 on Wednesday, after falling as much as 19% earlier in the session. At that low, the drop had erased more than €8 billion of the company's market value and was on course to be the stock's largest one-day fall since December 2023. In New York, where the Nasdaq-listed shares opened at $831.23, they were down 11% at $826.24 at 9:42 a.m. Eastern time, compared with Wednesday's close of $928.44.