Phase 4 OCTAGON Trial to Test Rapid Steroid Taper With Ravulizumab

A new phase 4 study, OCTAGON, will evaluate whether a rapid, predefined oral corticosteroid (OCS) tapering schedule can be used safely in patients with generalized myasthenia gravis (gMG) who are being treated with ravulizumab, a complement C5 inhibitor already approved for the condition. Researchers presented the trial-in-progress design at the 2026 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting and MGFA Scientific Session, held this week in Orlando, Florida.¹

OCTAGON is a phase 4, prospective, multicenter, single-arm study (NCT07221838), sponsored by Alexion, testing whether a rapid, predefined OCS-tapering schedule can be used safely in adults with anti-acetylcholine receptor antibody-positive (AChR-Ab+) gMG already stabilized on ravulizumab. Investigators noted that treatment guidelines recommend steroid-sparing strategies, but clinical practice often relies on prolonged OCS tapers involving greater steroid exposure and adverse-event risk than faster tapering; ravulizumab's approval, they said, enables OCS reduction or discontinuation while maintaining symptom control.

Planned enrollment is approximately 75 adults with gMG receiving ravulizumab every 8 weeks who are on a stable OCS regimen averaging at least 7.5 mg/day for 4 weeks or longer. Patients with a baseline OCS dose of 7.5 to 10 mg/day will taper by 2.5 mg/day every 4 weeks down to 2.5 mg/day, then by 1.25 mg/day every 4 weeks until completion; those starting above 10 mg/day will taper by 5 mg/day every 2 weeks down to 10 mg/day before following the same lower-dose schedule.

The primary endpoint is the proportion of patients who discontinue OCS entirely or reduce to 5 mg/day or less and maintain that status for at least 4 weeks without gMG clinical deterioration, assessed over approximately 32 weeks. Secondary endpoints include change in MG-ADL score, complete OCS discontinuation, percentage dose reduction from baseline, quality of life on the MG-QoL-15r, and cumulative glucocorticoid toxicity measured by the Glucocorticoid Toxicity Index. The trial began enrolling in March 2026 across 12 sites in 4 countries and remains open.^1,2

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“OCTAGON addresses a critical unmet need for an evidence-based rapid OCS tapering schedule in patients with gMG," lead author Benjamin Yungher, PhD, of Alexion, AstraZeneca's rare disease group, and colleagues, wrote.¹ “Results will provide a framework for effective and safe OCS treatment management in the targeted immunotherapy era.”

Ravulizumab's approval history in gMG

The FDA approved ravulizumab in April 2022 for adults with AChR-Ab+ gMG, making it the first long-acting C5 complement inhibitor available for the condition; it is dosed as a weight-based loading dose on day 1 followed by weight-based maintenance infusions every 8 weeks beginning on day 15.³

Approval was based on the phase 3 CHAMPION-MG trial, in which ravulizumab reduced MG-ADL score by 3.1 points versus 1.4 with placebo and QMG score by 2.8 points versus 0.8 (P <.001 for both) over 26 weeks, with 30% of ravulizumab-treated patients achieving a clinically meaningful 5-point or greater QMG improvement compared with 11.3% on placebo (P =.005).⁴

"Earlier intervention can preserve function and quality of life," said James F. Howard Jr., MD, professor of neurology at the University of North Carolina at Chapel Hill, at the time of approval.³

Ravulizumab (Ultomiris) first reached the market in December 2018, when the FDA approved it for adults with paroxysmal nocturnal hemoglobinuria; the agency expanded that approval to atypical hemolytic uremic syndrome in October 2019, to a reformulated version with a shorter infusion time in October 2020, and to children and adolescents with paroxysmal nocturnal hemoglobinuria in June 2021.⁵

The gMG approval followed in April 2022, and the FDA most recently expanded ravulizumab's label in March 2024 to adults with anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder, based on data showing the drug could reduce relapse risk by blocking the same terminal complement cascade targeted in its other indications.⁶

Click here for more AANEM 2026 coverage.

REFERENCES
1. Yungher B, Weiskopf E, Aguzzi R, Sabatella G. The phase 4 OCTAGON study investigating oral corticosteroid tapering in adult patients with generalized myasthenia gravis treated with ravulizumab: trial in progress. Presented at: 2026 AANEM Annual Meeting and MGFA Scientific Session; September 29-October 2, 2026; Orlando, FL.
2. A study to investigate OCS tapering in adult participants with generalized myasthenia gravis treated with ravulizumab (OCTAGON). ClinicalTrials.gov identifier: NCT07221838. Accessed September 29, 2026. https://clinicaltrials.gov/study/NCT07221838
3. Ultomiris approved in the US for adults with generalized myasthenia gravis. News release. Published April 28, 2022. Accessed September 29, 2026. https://www.astrazeneca.com/media-centre/press-releases/2022/ultomiris-approved-in-the-us-for-adults-with-generalized-myasthenia-gravis.html
4. Vu T, et al. Terminal complement inhibitor ravulizumab in generalized myasthenia gravis. NEJM Evid. Published 2022. doi:10.1056/EVIDoa2100066
5. Drugs.com. Ultomiris (ravulizumab-cwvz) FDA approval history. Accessed September 29, 2026. https://www.drugs.com/history/ultomiris.html
6. Ultomiris approved in the US for the treatment of adults with neuromyelitis optica spectrum disorder (NMOSD). News release. Published March 25, 2024. Accessed September 29, 2026. https://www.astrazeneca.com/media-centre/press-releases/2024/ultomiris-approved-in-the-us-for-nmosd.html