FDA Approves Autoinjector for Self-Administered Zilucoplan in Generalized Myasthenia Gravis

The FDA has approved a once-daily autoinjector for zilucoplan (ZILBRYSQ), giving adults with generalized myasthenia gravis (gMG) a second self-administered delivery option for the complement inhibitor. UCB, which markets the drug, said the approval is supported by bioequivalence and usability data gathered across three separate studies.¹

Zilucoplan has been available since 2023 as a self-administered prefilled syringe for adults with gMG who are anti-acetylcholine receptor (AChR) antibody positive; the new autoinjector is designed to automatically deliver a pre-defined dose when pressed against the skin, giving patients and caregivers a second, portable option for daily dosing.

“This approval is the answer to a question on which we've been relentlessly focused: how do we continue to improve an already effective therapy for use every single day?” Kimberly Moran, PhD, SVP and head of US rare diseases at UCB, said in a statement.¹ “As the first treatment to be approved as a once-daily autoinjector option for adults living with gMG in the U.S., ZILBRYSQ now provides the same therapy via another administration option.”

Bioequivalence and self-administration data

UCB noted the autoinjector's approval rests on two company-sponsored studies, plus a separate usability study. In DV0012, a phase 1, open-label, single-center, two-period crossover study, 14 healthy volunteers received zilucoplan through both the autoinjector and the prefilled syringe to establish bioequivalence between the two devices.^1,2

In DV0013, a phase 3b, open-label, multicenter study, 31 adults with gMG self-administered zilucoplan by autoinjector once daily; complete dose delivery was achieved in 99.8% of 449 total autoinjector uses, and patients reported high satisfaction with the device. Self-administration was generally well tolerated, with injection-site pain, reported in 3 patients (9.7%), as the most common treatment-emergent adverse event.^1,2

Usability without training

A separate human factors validation study enrolled 100 participants, including patients with gMG or ocular symptoms, caregivers, and healthcare professionals, each categorized as either experienced with injections or injection-naive. Ninety percent of participants completed an injection with the autoinjector successfully on their first attempt without any training.^1,3

Donatello Crocetta, global head of medical affairs and chief medical officer at UCB, said the device needed to clear that usability bar without compromising the drug's established effectiveness. “From a medical standpoint, it was essential to confirm that this added administration option didn't come at the expense of safety and efficacy,” he said. “The data supporting the autoinjector's complete dose delivery show that this option continues to offer effective treatment for patients.”

The pivotal trial behind the original approval

Zilucoplan's original approval was based on RAISE, a randomized, double-blind, placebo-controlled phase 3 trial in which the macrocyclic peptide, which blocks complement component 5 (C5) at the neuromuscular junction, improved measures of myasthenia gravis-specific disease activity and quality of life compared with placebo over 12 weeks.⁴ The FDA approved zilucoplan for adults with AChR antibody-positive gMG in October 2023, and UCB has continued to study the drug's long-term use in the years since.⁵

Safety considerations

Like other complement inhibitors, zilucoplan carries a boxed warning for serious, potentially fatal meningococcal infections, and it is available only through a restricted program under a Risk Evaluation and Mitigation Strategy. The FDA recommends patients complete or update meningococcal vaccination at least 2 weeks before starting treatment unless the risk of delaying therapy outweighs the risk of a meningococcal infection.¹

UCB said it expects the autoinjector to become commercially available in the first quarter of 2027. The company markets a second gMG therapy, Rystiggo (rozanolixizumab-noli), a subcutaneously infused antibody targeting the neonatal Fc receptor that is approved for adults who are AChR or anti-muscle-specific tyrosine kinase (MuSK) antibody positive, giving physicians two UCB-made options with different mechanisms for the disease.

REFERENCES
1. UCB announces U.S. FDA approval for ZILBRYSQ (zilucoplan) autoinjector self-administration for adults living with generalized myasthenia gravis. News release. UCB. Published October 16, 2026. Accessed October 16, 2026. https://www.ucb.com/newsroom/press-releases/article/ucb-announces-us-fda-approval-for-zilbrysqr-zilucoplan-autoinjector-self-administration-for-adults-living-with-generalized-myasthenia-gravis
2. Petrulis M. Bioequivalence and effectiveness of autoinjector-delivered, self-administered zilucoplan compared with pre-filled syringe. Poster presented at: American Academy of Neurology (AAN) Annual Meeting 2026; April 18-22, 2026; Chicago, IL. Poster P11-9-009.
3. Karali S, Domanska B, Savic N, et al. Usability of zilucoplan auto-injector in generalised myasthenia gravis: a human factors validation study. Poster presented at: International Congress on Neuromuscular Diseases (ICNMD) 2026; July 7-11, 2026; Florence, Italy. Poster PP01.229.
4. Howard JF Jr, Bresch S, Genge A, et al. Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Neurol. 2023;22(5):395-406. doi:10.1016/S1474-4422(23)00080-7
5. UCB announces US FDA approval of ZILBRYSQ (zilucoplan) for the treatment of adults with generalized myasthenia gravis. News release. UCB. Published October 17, 2023. Accessed October 16, 2026. https://ucb.com/newsroom/press-releases/article/ucb-announces-us-fda-approval-of-zilbrysqr-zilucoplan-for-the-treatment-of-adults-with-generalized-myasthenia-gravis