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Since late 2021, a bevy of targeted generalized myasthenia gravis therapies has crossed the regulatory finish line in the U.S., beginning with argenx’s FcRn blocker Vyvgart four years ago and most recently culminating in April’s approval of Johnson & Johnson’s Imaavy. Amid a swell of regulatory successes in the myasthenia gravis arena this decade, Amgen is wading into the fray with a new indication for its monoclonal antibody Uplizna.Thursday, the FDA greenlighted Uplizna (inebilizumab) to treat generalized myasthenia gravis (gMG) in adults who are anti-acetylcholine receptor (AChR) and anti-muscle specific tyrosine kinase (MuSK) antibody positive. After two loading doses, Uplizna for gMG is administered just twice a year, Amgen noted in a Dec. 11 press release.Myasthenia gravis is a rare autoimmune disorder that hampers neuromuscular communication, which can in turn cause fluctuating muscle weakness, Amgen explained. The condition—which is estimated to affect about 80,000 to 100,000 people in the U.S. by Amgen’s reckoning—is thought to be primarily driven by AChR and MuSK autoantibodies, which are produced by CD19+B cells, the company added.Since late 2021, a bevy of targeted gMG therapies has crossed the regulatory finish line in the U.S. and beyond, beginning with argenx’s FcRn blocker Vyvgart (efgartigimod) four years ago and most recently culminating in April’s approval of Johnson & Johnson’s Imaavy (nipocalimab), prior to the Uplizna nod."This approval marks a significant advancement for people living with gMG," Jay Bradner, M.D., Amgen’s executive vice president of R&D, said in a statement."By selectively targeting CD19-positive B cells, Uplizna offers a new approach to treatment that addresses a biological root cause of disease,” he continued. “Uplizna is conveniently dosed twice a year and delivers durable efficacy, helping people manage debilitating symptoms that can compromise daily function – including trouble breathing, speaking and seeing." Uplizna’s efficacy in gMG is thought to lie in its “targeted and sustained” depletion of cells essential to the underlying disease process, which Amgen defined in its release as autoantibody-producing CD19+ B cells, including plasmablasts and some plasma cells.The FDA gave Uplizna the thumbs-up after reviewing data from Amgen’s phase 3 Mint trial. At the study’s 26-week mark, treatment with Uplizna was associated with a 1.9-point difference on the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale—a common measure of myasthenia gravis symptoms—versus placebo, Amgen noted in its release. Specifically, Uplizna led to a 4.2-point reduction on the scale versus a 2.2-point reduction in the trial’s control cohort.The drug’s benefits persisted through an entire year in the trial among patients in the AChR-positive subgroup, Amgen pointed out.The California pharma also touted a steroid taper baked into the study’s protocol, noting that by Week 26, 87.4% of patients on Uplizna and 84.6% of those on placebo had curbed their steroid dose to 5 mg or less per day.The approval marks Uplizna’s second this year and third overall. Back in April, the antibody drug was cleared by the FDA to treat adults with immunoglobulin G4-related disease, building on the drug’s original 2020 green light to treat certain neuromyelitis optica spectrum disorder patients.Uplizna is entering the gMG market at a busy time. Aside from argenx’s Vyvgart and J&J’s Imaavy, UCB’s Rystiggo and Zilbrysq and AstraZeneca and Alexion’s Soliris and Ultomiris also carry recent approvals in the indication. Meanwhile, argenx scored a thumbs-up for a subcutaneous version of its drug, dubbed Vyvgart Hytrulo, back in 2023.In terms of competitive advantages, Amgen appears to be leaning heavily on the potential convenience edge that Uplizna’s twice-a-year dosing could provide. The treatment schedules for the other targeted gMG therapies on the market tend to require maintenance dosing every few weeks, with the timing sometimes dependent on factors related to each patient.Moreover, analysts at Citi Research noted on Thursday that Uplizna's CD-19 targeting mechanism, coupled with its efficacy across gMG subgroups, dosing convenience and steroid-sparing potential, could present "unique differentiation" in the crowded market. Uplizna could be looking at a $1.7 billion sales opportunity in gMG by 2030, the Citi team added. With the approval of Imaavy in April, meanwhile, J&J asserted that its label covered the “broadest population of people living with gMG,” banking those claims in large part on the fact that its drug is approved not only in adults but in people ages 12 and up.Elsewhere, argenx recently scored an FDA nod for a prefilled syringe format of Vyvgart Hytrulo that can be administered at home. And the company is homing in on a potential approval in seronegative patients, which describes the minority of people with gMG who lack detectable AChR or MuSK antibodies in their blood, making the already rare autoimmune condition even trickier to diagnose.Editor's note: This story has been updated with commentary from a Dec. 11 analyst note.  

Inflammation is like a fire you just can’t put out—inflammatory disorders are chronic conditions after all. If your house is ablaze and you know a gas leak is the cause, dousing the entire home isn’t a targeted way to stop what’s feeding the flames, says John Puisis, co-founder and CEO of Cour Pharmaceuticals. He compares his startup’s drugs to stopping fire at the source. “We go into the basement, and we turn off the fuel valve completely,” Puisis said. Cour’s technology found early validation in the hands of a large pharmaceutical company that picked up one of the biotech’s programs and is currently testing it in mid-stage clinical trials. Now the Chicago-based startup wants to do the same with its internal pipeline and it has raised $105 million for its plans. In doing so, Cour aims to show how its approach to inflammation stands apart from the company’s immunology peers. One of the hottest areas of autoimmune disease research involves harnessing regulatory T cells, or Tregs. These cells in our bodies counteract excessive immune responses. A slew of Treg startups—Sonoma Biotherapeutics, Gentibio, Abata Therapeutics, Quell Therapeutics, and Tr1X—are engineering Tregs to treat a variety of inflammation-driven conditions. The jury is still out on these experimental cell therapies, which have limited, if any, clinical data so far. But Puisis, whose experience includes serving as CEO of autoimmune disorder drug developer Tolera Therapeutics, said one problem with Tregs is that immune suppression from these engineered cells can spread beyond their targets, leading to unwanted effects. “What’s interesting with us versus the others—I won’t name them—they’re doing generalized Tregs, you can actually get off-target spreading,” Puisis said. “We’re basically telling the body ‘don’t attack these cells anymore.’” Cour does not engineer cell therapies. The company works with nanoparticles that trick the body into thinking that they’re cells. Inside of these particles is an antigen for a particular autoimmune disease. The composition of all Cour drug candidates is the same, with the exception of the disease-causing antigen encapsulated within. Cour’s nanoparticles are about the same size as a cell, which is important as they circulate throughout the body. Too large, and they could cause clotting problems, Puisis said. Too small, and the immune system won’t recognize them. Recognition is key to how Cour’s therapies reprogram the immune system, Puisis said. Immune cells that provide surveillance for the immune system pick up the nanoparticles and take them to the spleen, which makes white blood cells, and the liver, which plays a role in the adaptive immune response. Released in these organs without any accompanying inflammatory signals, the immune system perceives the antigens as belonging to the body. The body then produces Tregs that migrate to the site of disease to tamp down immune responses to that antigen. Cour’s technology is based on decades of research by Stephen Miller, a professor of microbiology-immunology at Northwestern University. The startup’s initial focus was celiac disease, an immune response to gluten in certain foods. Preclinical research presented and published in 2015 described how nanoparticles can be generated from biocompatible compounds and used to deliver an antigen to restore immune tolerance. Soon after, Takeda Pharmaceutical began a partnership on the Cour celiac disease therapy. Takeda licensed this therapy in 2019 and is now responsible for its clinical development. Meanwhile, Ironwood Pharmaceuticals holds an option to license a different Cour therapy for primary biliary cholangitis, a rare autoimmune disease affecting the bile ducts of the liver. Puisis isn’t ruling out more pharma alliances, but for now, he said Cour is focusing on developing its own pipeline. Cour’s nanoparticles can encapsulate multiple antigens to address diseases driven by more than one antigen, such as type 1 diabetes. That disease and the rare muscle disorder myasthenia gravis are Cour’s lead indications. Cour selected these diseases because the few available therapies for them leave patients wanting for something better, Puisis said. Drug hunters have pursued antibody therapies for both diseases. The 2022 approval of Provention Bio’s antibody Tzield made that therapy the first FDA-approved treatment for delaying type 1 diabetes progression. Sanofi acquired Provention for $2.9 billion last year. In myasthenia gravis, Argenx markets two antibody fragments, Vyvgart and Hytrulo. Last year, UCB won FDA approval for two myasthenia gravis therapies, Rystiggo and Zilbrysq. While Rystiggo is an antibody that works similarly to Argenx’s drugs, Zilbrysq is a peptide that addresses a different target. The approved type 1 diabetes and myasthenia gravis therapies are chronic treatments, like regular applications of fire suppression that do not extinguish the fire for good. In addition to potentially better efficacy, Cour aims to offer patients long-lasting effects. Puisis said preclinical research suggests the effect of Cour’s therapies last for the lifetime of the animal. To be fair, developers of engineered Tregs also say their therapies may offer long-lasting effects. The durability of both types of treatments still must be shown in human testing. But one advantage that Cour could have over Tregs is manufacturability. Making a therapy from nanoparticles is less expensive and more easily scalable compared to engineering a patient’s cells or donor cells into cell therapies. Cour’s Series A financing was co-led by Lumira Ventures and Alpha Wave Ventures. Other investors include Roche Venture Fund; Pfizer, through its Pfizer Breakthrough Growth Initiative; Bristol Myers Squibb; Angelini Ventures; and the JDRF T1D Fund. Puisis said the financing will support the advancement of both of its programs through Phase 2a clinical development. As for Cour’s name, Puisis said it’s derivative of the word “courage” and is the brainchild of one of the startup’s scientists. “You need a lot of courage to be in biotech and to be in the discovery business,” Puisis explained. Photo by Flickr user Peter Hill via a Creative Commons license