Efgartigimod/Hyaluronidase

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.