argenx BV

Argenx is discontinuing its late-stage UplighTED studies of subcutaneous efgartigimod in adults with moderate to severe thyroid eye disease. While argenx has been able to demonstrate the merit of its FcRn drug Vyvgart in multiple autoimmune indications, not every shot in the clinic is destined to land.Now, facing that fact in thyroid eye disease (TED), argenx is walking away from a set of trials.Argenx is discontinuing its late-stage UplighTED studies of subcutaneous efgartigimod in adults with moderate to severe TED, the Dutch biopharma announced Monday. Efgartigimod is the generic name for Vyvgart, which is approved both as an infusion and as an injectable under the brand name Vyvgart Hytrulo, with the latter being the format tested in argenx’s study.The drugmaker is calling it quits on the Vyvgart Hytrulo TED program following a recommendation from an independent data monitoring committee, which urged argenx to stop the trials for futility after reviewing data at a preset interim analysis.There was a small silver lining insofar as Vyvgart Hytrulo’s safety and tolerability looked favorable in the trials, with no new safety flags cropping up, argenx pointed out. The company’s stock was down more than 5% in morning trading Dec. 15.The futility evaluation came at the studies’ 24-week mark, argenx explained. The company says it plans to parse through the data, once available, so it can better understand the “studies’ outcome and uncover key biological insights that may inform future research in TED.”The company noted that it will share the results at an upcoming medical meeting, as well. TED, an autoimmune disease affecting the eye socket, can cause muscles that control the eye and fat behind the organ to grow abnormally, and it can also lead to orbital inflammation. This can in turn cause proptosis (when the eyes bulge from their natural position), diplopia (double vision) or, in severe cases, vision loss, argenx explained in its release.The company’s UplighTED studies specifically looked at TED patients with the autoimmune thyroid conditions Graves’ disease or Hashimoto’s thyroiditis. The primary endpoint of the studies—which pitted Vyvgart Hytrulo against placebo—concerned the percentage of patients classified as “proptosis responders” at Week 24, argenx said.The trials also looked at secondary metrics such as the change in proptosis measurement from baseline, change in total score on a quality-of-life measure known as Graves’ Orbitopathy Quality of Life, and the percentage of trial participants whose diplopia had resolved, all at 24 weeks.“We are disappointed the studies did not meet our desired outcome and we especially empathize with patients who are living with TED and seeking new therapies for this challenging disease,” Luc Truyen, M.D., Ph.D., argenx’s chief medical officer, said in a statement. “We had pre-planned this futility analysis as it provides a meaningful interim evaluation of observed patient outcomes and enables us to responsibly evaluate the study’s future likelihood of success.”Since the original approval of infused Vyvgart in generalized myasthenia gravis (gMG) in late 2021, argenx has largely made good on its thesis that the asset has potential in a range of autoimmune diseases. For its part, Vyvgart Hyrulo—the drug’s subcutaneous formulation—is broadly approved in gMG and chronic inflammatory demyelinating polyneuropathy around the world, and the drug also boasts a nod to treat primary immune thrombocytopenia in Japan. In the clinic, argenx is trialing efgartigimod in numerous autoimmune diseases, from ocular myasthenia gravis and myositis to Sjogren’s disease and systemic sclerosis, among other potential indications.In the nearer term, the Dutch drugmaker is aiming for an FDA nod for both subQ and infused Vyvgart in the subset of gMG patients who are seronegative, meaning their condition lacks detectable levels of certain antibodies that are often characteristic of the disease. With results from a positive phase 3 seronegative trial in hand, argenx has said it plans to file for an FDA review in the indication by the end of 2025. 

Argenx said Monday it will stop late-stage trials of its autoimmune disease shot Vyvgart Hytrulo in thyroid eye disease after an interim analysis found the studies were unlikely to succeed. The independent data monitoring committee overseeing the twin UplighTED studies had recommended that they be stopped for futility, the Dutch biotech said . Argenx’s stock $ARGX was down by as much as 7% in early trading. The Phase 3 trials were due to enroll a total of 246 patients with thyroid eye disease associated with the autoimmune thyroid conditions Graves’ disease or Hashimoto’s thyroiditis. The trials were designed to prove a benefit for Vyvgart Hytrulo over placebo on proptosis, the eye bulging that is characteristic of the disorder, after six months of therapy. The futility evaluation was based on unblinded data from a subset of patients who had been in the trials for six months. Argenx said it would sift through the data to better understand the studies’ outcomes and try to find “key biological insights” that could inform future research in the disease. It said no new safety signals were identified with the asset, and that results of the trials would be presented at a conference in the future. Vyvgart Hytrulo is an injected combination of a neonatal Fc receptor blocker called efgartigimod with hyaluronidase. It is approved as a therapy for certain adults with generalized myasthenia gravis, and also for another neurological condition called chronic inflammatory demyelinating polyneuropathy. Separately, intravenous efgartigimod is approved as Vyvgart in generalized myasthenia gravis. It is also greenlit in Japan for primary immune thrombocytopenia, a disease in which the patient’s immune system attacks their platelets, potentially causing bruising and bleeding. The injected form of the drug is also being studied in a suite of other immune conditions. This summer, argenx touted Phase 2 data in Sjögren’s syndrome, in which patients have difficulty producing fluids like tears and saliva; and myositis, a form of muscle inflammation. It is also conducting early-stage studies in systemic sclerosis, a rheumatic disease where patients overproduce and accumulate collagen; and antibody-mediated rejection, a major cause of kidney transplant failure.

Argenx's hopes of securing another indication for its sole marketed drug, the human IgG1 antibody fragment efgartigimod alfa, suffered a blow on Monday after the company announced that Phase III studies in thyroid eye disease (TED) will be discontinued due to futility. The news sent argenx's shares down as much as 9%.First approved under the name Vyvgart (efgartigimod alfa-fcab) in 2021 for the treatment of generalised myasthenia gravis, the neonatal Fc receptor blocker has gone on to secure additional indications — including chronic inflammatory demyelinating polyneuropathy — and reformulation into a subcutaneous version called Vyvgart Hytrulo (efgartigimod alfa/hyaluronidase-qvfc). The products, which together brought in $2.2 billion in sales last year, have positioned argenx as a takeover target, given that analysts see use across all indications potentially topping $10 billion."While thyroid eye disease could have added $800 million to our current $11 billion peak sales estimates, it only represents a minor part of our Vyvgart valuation," remarked Van Lanschot Kempen analyst Sebastiaan van der Schoot.The Phase III UplighTED studies evaluated the subcutaneous formulation of efgartigimod versus placebo in adults with moderate-to-severe TED. The trials' primary endpoint is measured as the percentage of participants who were proptosis responders at week 24, while key secondary goals include change in proptosis measurement in the study eye from baseline up to week 24, change in the total Graves' Orbitopathy Quality of Life (GO-QoL) score from baseline up to week 24, and percentage of participants with resolution of diplopia at week 24.Argenx said that the decision to halt the studies follows a pre-specified interim analysis and the recommendation from an Independent Data Monitoring Committee (IDMC) that conducted a futility evaluation of unblinded data from patients completing 24 weeks. The company noted that no new safety signals were identified, while further data will be shared at a future medical meeting.Although the setback in TED will knock a little off forecasts for Vyvgart/Vyvgart Hytrulo, attention will now turn to three other late-stage studies for the drug that are set to readout in 2026.Bloomberg Intelligence analyst Michael Shah said that the failure in TED is "unexpected and rules out a patient population of 100,000 in the US," with it placing an "added burden on delivering successful pivotal readouts" in ocular myasthenia gravis, myositis and primary immune thrombocytopenia.