Efgartigimod/Hyaluronidase

With its latest trial readout for under-the-skin efgartigimod, argenx is adding another feather to the FcRn blocker’s cap. On Monday, the Dutch immunology company announced the successful readout of its phase 2/3 Alkivia study testing the subcutaneous version of its drug, known commercially as Vyvgart Hytrulo, in adults with autoimmune myositis. The trial—which enrolled 264 patients on background therapy with either immune-mediated necrotizing myopathy (IMNM) or dermatomyositis (DM)—met its primary endpoint: Patients in a combined cohort on argenx’s drug achieved a statistically significant and clinically meaningful 15.4-point greater improvement on average on a measure of clinical efficacy at 52 weeks versus placebo, the company said in an Aug. 17 release. Argenx stressed the swiftness with which its drug started to help patients, too, showing improvements over placebo beginning at around a month, which the company said were “statistically significant and sustained through the full year of treatment, even with steroid tapering.” One of multiple immunology indications argenx is either pursuing or has already captured with Vyvgart, autoimmune myositis is a highly varying disease spectrum marked by chronic inflammation and progressive muscle weakness. In certain subtypes, patients can also struggle with dermatological issues like skin rashes, though proximal muscle weakness is a “hallmark clinical feature” across all manifestations of the rare condition, argenx explained. There are some 100,000 people in the U.S. estimated to be living with autoimmune myositis, including roughly 20,000 with IMNM and 40,000 with DM—the subtypes specifically tested for in the company’s trial. While multiple companies are vying to deliver the first targeted autoimmune myositis drug, no such therapy currently exists in the U.S., where standard treatment leans on corticosteroids and broad immunosuppressants. In making the case for a drug like Vyvgart in myositis, argenx flagged the well-known side effects associated with long-term use of those limited present treatment options, including potential metabolic, heart, musculoskeletal and infectious complications. As with the other autoimmune indications where argenx has aimed Vyvgart, the company suspects that the contribution of IgG autoantibodies in myositis disease activity—and Vyvgart’s ability to reduce those autoantibodies and preserve other immune function as a selective FcRn blocker—gives it a shot at bringing a meaningful treatment advancement forward. Breaking down the reported win, in the combined pool of IMNM and DM patients, Vyvgart Hytrulo charted a 15.4-point greater improvement in mean total improvement score (TIS) at the trial’s one-year mark versus placebo. That improvement was based on six measures, argenx explained, spanning muscle strength, everyday physical function and disease activity beyond the muscle. The company also noted that it observed improvement in skin disease activity in the DM cohort specifically. Across subtype analyses, the win was not quite so absolute. While the primary endpoint of mean TIS at week 52 was also met with IMNM patients on Vygart Hytrulo at a 14.8-point greater improvement over placebo, the improvement of 14.5 points observed in the DM-specific subgroup was, while clinically meaningful, not statistically significant. Still, argenx and at least one set of analysts appear encouraged by the readout all the same, with the team at Citi writing in a note Monday that the statistical miss in DM—driven by previously communicated underpowering—still showed a magnitude of TIS benefit in line with the IMNM population and on par with rival investigational asset brepocitinib , a TYK2/JAK1 inhibitor from Roivant. “This sets argenx up with a potential path forward in DM,” wrote the team at Citi. The analysts were otherwise effusive about the data in IMNM patients, which it noted represent “a blockbuster indication in its own.” Citi is currently forecasting peak U.S. sales of around $1.9 billion for Vyvgart in IMNM. “The patient response to efgartigimod was durable and multidimensional,” Luc Truyen, M.D., Ph.D., argenx’s chief medical officer, said in a statement Monday. He pointed to the fact that “separation from placebo emerged early and held through a full year of treatment, with a treatment effect of comparable magnitude in IMNM and DM,” noting that “[t]his confirms that pathogenic IgG autoantibodies are key drivers of autoimmune myositis.” Argenx added that it plans to share detailed results from its Alkivia study at an upcoming medical conference. The company also aims to take the data to the FDA, the Citi team wrote in its note. Since the original nods for Vyvgart and its subQ counterpart Vyvgart Hytrulo in 2021 and 2023 to treat generalized myasthenia gravis, the therapy has entered additional indications like chronic inflammatory demyelinating polyneuropathy in the U.S. and branched out into diseases like primary immune thrombocytopenia in Japan, all the while continuing to generate evidence in a range of other potential autoimmune niches. Back in February, argenx posted another late-stage win for Vyvgart in the key ocular myasthenia gravis space, with the drug helping improve patients’ vision by a statistically significant margin. That trial victory prompted argenx to put the drug forward for a potential FDA approval in the indication. Meanwhile, the company in May clinched an FDA nod expanding Vyvgart Hytrulo into all serotypes of adult patients with generalized myasthenia gravis, essentially locking down the entirety of the patient population for the weakness-causing neuromuscular disorder. Still, it hasn’t been entirely smooth sailing for Vyvgart in recent months. Late last year, the drug came up short in a phase 3 study in thyroid eye disease. The rare miss motivated argenx to call it quits on a set of trials in its UplighTED program.

Shares for Argenx soared over 13% Monday morning after the company announced positive data from a Phase 3 trial for a rare autoimmune condition that could expand use of its blockbuster drug Vyvgart.The Dutch biopharmaceutical company said Mondayan under-the-skin injection version of Vyvgart, called Vyvgart Hytrulo, met its primary endpoint in a late-stage combined study of people with myositis, a rare autoimmune disease that attacks the muscles and has limited treatments. The company said that Vyvgart, when compared to placebo, showed improvements in two subsets of the disease, as measured by a scale evaluating muscle strength and physical health known as Total Improvement Score, or TIS.For people living with myositis, the goal is straightforward: regain strength and function, and get off long-term steroids. Until now we have had limited targeted therapies to offer patients, said Rohit Aggarwal, the co-director of the Myositis Center at the University of Pittsburgh and an ALKIVIA investigator, in a statement.The study enrolled people with two forms of myositis known as dermatomyositis, or DM, which leads to skin rash, and immune-mediated necrotising myopathy, or IMNM, a more aggressive form of the disease that breaks down muscle cells with no approved treatment options, and an approximate patient population of 20,000.When compared to placebo, Vyvgart displayed rapid and sustained benefit starting as early as week four in adults with the condition and lasting a year with steroid tapering. Vyvgart also demonstrated a 15.4-point greater improvement in mean TIS after 52 weeks, according to Argenx. Safety was consistent with prior studies.Results were driven by strong efficacy data in those with the IMNM form of myositis. And while Vyvgart displayed similar meaningful improvement in those with DM, it did not reach statistical significance.However, those results did not prompt investors to falter. Leerink Partners analyst Thomas Smith told clients in a note Monday the results are a positive outcome representing a meaningful expansion opportunity for the Vyvgart franchise, particularly in the IMNM subset where there are no approved therapies and profound unmet need.The blockbuster Vyvgart has made Argenx one of biotechs most valuable companies, with a market capitalization now topping $60 billion. The drug, which reduces the antibody immunoglobulin G, gained its first clearance for the treatment of the autoimmune condition generalized myasthenia gravis, or gMG, in 2021. The drug has since been formulated as a subcutaneous injection and gained label expansion in another autoimmune condition, generating billions for Argenx and, so far this year,climbing close to $2.9 billionbetween January and June.Argenx has been on a mission to expand the drugs use, but has already faced setbacksin other conditions.The latest study results now provide another expansion opportunity for Vyvgart, with RBC Capital Markets analyst Luca Issa calling the trial a big win for the company.Issa added in a note Monday that while the drug missed its primary goal in DM, he believes the drug missed because of small sample size, and will ultimately gain approval either on this trial or a new larger trial replicating this evidence should the FDA decide to play hard ball.Argenx said detailed results will be presented at an upcoming medical meeting. '