Cemdisiran

iStock, quantic69 After decades without much movement, a handful of new treatments for this rare autoimmune disease are now approved, and several companies, including argenx and Regeneron, have recently released promising late-stage trial results. A new generation of drugs is revolutionizing the treatment of myasthenia gravis, a chronic, debilitating autoimmune condition in which communication breaks down along the neuromuscular junctions that bridge the signals between the brain and muscles. In less than a decade, the number of myasthenia gravis (MG)-specific therapies available to patients has bloomed, sparking double-digit growth in the global market and prompting analysts to project revenues exceeding $10 billion by 2033. Now, argenx, UCB, Amgen , Regeneron and more are vying for a share of this niche market. “Until recently, we hadn’t seen a newly approved MG therapy in many decades,” Tom Ragole, a neuromuscular neurologist at the UCHealth Neurosciences Center in Colorado, told BioSpace . But in the past eight years, starting with AstraZeneca’s Soliris , five new MG-specific therapies have hit the market, and today, several groups are launching late-stage clinical trials—so many that it has sometimes been hard to recruit enough patients for them all. “Part of it is that being on a therapy often excludes you from other trials, but it’s also just that you need a certain disease burden, and we have so many options now for treating people that they no longer qualify.” While myasthenia gravis is among the most commonly diagnosed conditions affecting neuromuscular junctions, it remains a rare disease, afflicting roughly 37 out of every 100,000 people in the U.S. Early symptoms often manifest in the head—including drooping eyelids, double vision and facial weakness—but can eventually expand to other parts of the body in a form known as generalized myasthenia gravis (gMG). The underlying causes of MG remain murky, and there is no cure, but researchers are beginning to understand more about the disease’s drivers. Broadly, MG is mediated by a class of abnormal IgG antibodies that target receptors or proteins in the neuromuscular junction, most commonly the acetylcholine receptor (AChR), muscle-specific kinase and lipoprotein receptor-related protein 4. Patients can be positive for some, but not all, of these antibodies, or negative for all three, suggesting additional targets that researchers have yet to identify. Ragole said treatments have historically pulled from the toolkit leveraged for many autoimmune disorders: corticosteroids, immunosuppressants and plasma exchanges. But while such treatments can be effective, they remain the equivalent of a Band-Aid, according to Ragole, and it’s unclear whether steroid-based therapies have long-term side effects. Other fields, notably rheumatology, have already moved away from high-dose steroids and toward more targeted therapies, Ragole said, and he’s been pleased to see the surge in interest for myasthenia gravis drugs that do the same. “There’s definitely been a lot of movement on the front of these more targeted therapies,” he said. “MG is a disease that varies so much from patient to patient. The more options we have, the better I see things going moving forward.” The New Guard This new generation of drugs draws on scientists’ growing understanding of myasthenia gravis, targeting one of two late-stage pathways in the disease’s progression: the complement system—part of the innate immune system—and neonatal Fc receptor (FcRn) signaling. In 2017, the FDA approved Soliris as the first MG-specific therapy. This so-called C5 complement inhibitor stops destruction of muscle receptors in the neuromuscular junction. A few years later, in 2021, immunology-focused argenx followed with a FcRn-targeted therapy called Vyvgart that degrades disease-causing antibodies. Three more approvals have since followed, including UCB’s C5 complement inhibitor Zilbrysq and FcRn therapy Rystiggo in 2023 and J&J’s Imaavy earlier this year. Despite the surge in MG approvals, research is not slowing down. In August, argenx reported positive results from a Phase III trial testing Vygart’s effectiveness in patients lacking the AChR antibody. According to the company, this population accounts for roughly 20% of patients with gMG, and they often experience a more severe disease burden. Gaining approval to treat this group would open the drug up to a further 11,000 patients, analysts at William Blair said in an Aug. 25 note. Also in August, Regeneron released Phase III results for its RNA-based candidate cemdisiran in patients with AChR-positive gMG. The study met its primary and secondary endpoints while only inhibiting the complement system by 74%, suggesting that patients could improve their quality of life without completely shutting down complement, “which otherwise is very important in defending us from infections,” Andres Sirulnik, head of the Hematology Clinical Development unit at Regeneron, told BioSpace. Several features of cemdisiran “represent improvements over existing MG therapies” that Regeneron hopes will push the drug candidate past its competitors, Sirulnik said. For example, existing treatments are dosed monthly or even daily, while cemdisiran is dosed via an injection that lasts for 12 weeks. That is something that patients will “absolutely” value, Ragole said. The Future: Near and Long-Term Despite the surge of activity in the MG space, experts agree that there’s still plenty of room for discovery and innovation. “There is still a high unmet need for patients in this disease,” Sirulnik said, adding that “a multipronged approach” is required. Long term, Ragole said it’s worth looking to other fields, such as cancer, that are increasingly leaning into cell-based therapies and precision medicine to further broaden options for patients. Treatments that leverage CD19+ B cells and CAR T cells have already been approved, as have synthetic, bispecific antibodies that bind to multiple targets simultaneously. “There’s increasing data that the types of breakthroughs we’ve seen in oncology are likely to be effective in some of these autoimmune disorders as well,” Ragole said. Near term, Argenx plans to supplemental application to expand Vyvgart into patients with triple-negative MG by the end of 2025. If successful, Vyvgart would enjoy the broadest label of all FcRn antagonists approved so far. Regeneron, meanwhile, will be submitting for FDA approval of cemdisiran in the first quarter of 2026. Omar Sinno , U.S. medical strategy lead for rare disease at UCB, said his company is also gearing up to share new updates. UCB continues to publish long-term safety and efficacy data on Zilbrysq and Rystiggo, including 10 abstracts to be presented at the upcoming American Association of Neuromuscular & Electrodiagnostic Medicine meeting , Oct. 29 to Nov. 1 in San Francisco. According to Sinno, UCB remains the only company offering two therapies that target different pathways, including the only complement inhibitor that can be used in conjunction with an FcRN therapy, allowing flexible treatment plans. Given the increasingly crowded treatment landscape, UCB is also partnering with the Myasthenia Gravis Foundation of America on a set of resources to help patients better understand and communicate their needs. “The thing about MG is that every case is actually different, and so having this breadth of treatments is good, but we need patients to understand their options,” Sinno told BioSpace . “Fortunately, patients are asking a lot more questions and advocating for themselves.”