Inebilizumab-cdon

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.