Global Phase 3 UPSTREAM MG Trial of Telitacicept Advances Enrollment in Generalized Myasthenia Gravis

An ongoing global, randomized, double-blind, placebo-controlled phase 3 trial (NCT06456580) evaluating telitacicept (Vor Bio) in adults with generalized myasthenia gravis (gMG) is actively enrolling across more than 13 countries, with topline results anticipated in mid-2027. The enrollment update was presented at the 2026 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting, held September 29 to October 2, in Orlando, Florida.¹

Telitacicept is a fully human TACI-Fc fusion protein that binds soluble B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL), preventing them from engaging their receptors (TACI, BCMA, and BAFF-R) on B cells. Investigators noted that BAFF plays a key role in allowing autoreactive B cells to bypass negative selection at immune checkpoints, contributing to the development of pathogenic B cells in autoimmune disease.

The study, presented by senior authorJames F. Howard Jr., MD, a professor of neurology at the University of North Carolina at Chapel Hill School of Medicine, and colleagues, will enroll approximately 180 adults with confirmed gMG. Eligible patients must have a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of at least 6, with less than 50% of the total score attributable to ocular symptoms, and a Quantitative Myasthenia Gravis (QMG) score of at least 8, with at least 4 items scoring 2 or higher at both screening and baseline.

Participants will be randomized 1:1 to receive weekly subcutaneous telitacicept 240 mg or placebo for 24 weeks, followed by an open-label extension. The primary end point is change from baseline in MG-ADL score at week 24. The authors noted that results from the global population are expected to extend the evidence for BAFF/APRIL inhibition with telitacicept to a broader population of adults with gMG.¹

The global program follows 2 studies conducted in China. In a multicenter, randomized, open-label phase 2 study, 29 patients with gMG received telitacicept 160 mg or 240 mg weekly in addition to standard-of-care therapy. Mean QMG score reductions from baseline to week 24 were 7.7 and 9.6 points in the 160-mg and 240-mg groups, respectively, with no adverse events leading to discontinuation and consistent reductions in serum IgA, IgG, and IgM levels.²

READ MORE: Gefurulimab Cuts Hospitalizations, Sustains Response in Phase 3 PREVAIL Trial of Myasthenia Gravis

In the subsequent randomized, double-blind phase 3 trial (NCT05737160), which enrolled 114 patients, MG-ADL scores decreased by 5.74 points with telitacicept 240 mg vs 0.91 points with placebo at week 24. A 3-point or greater MG-ADL improvement was observed in 98.1% of telitacicept-treated patients vs 12.0% of those receiving placebo. QMG scores improved by 8.66 points vs 2.27 points, respectively. The overall incidence of adverse events was similar between groups, and infection-related adverse events were less frequent with telitacicept (45.6% vs 59.6%).³

In the 48-week OLE, patients who remained on telitacicept showed a mean MG-ADL change of −7.5 points, while those who crossed over from placebo showed a change of −6.3 points. No new safety signals were reported. Telitacicept is currently approved in China for gMG, systemic lupus erythematosus, and rheumatoid arthritis.⁴

The gMG treatment landscape has expanded in recent years to include neonatal Fc receptor inhibitors, complement inhibitors, and B-cell–directed therapies. By targeting upstream cytokines involved in B-cell and plasma cell survival, telitacicept represents a mechanistically distinct approach. However, its relative place among these options has not been established.

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REFERENCES
1. Habib A, Pasnoor M, Vu T, et al. A phase 3 study to evaluate the efficacy and safety of telitacicept in patients with generalized myasthenia gravis: UPSTREAM myasthenia gravis trial design update. Presented at: 2026 AANEM Annual Meeting; September 29-October 2, 2026; Orlando, FL. Abstract 277.
2. Yin J, Zhao M, Xu X, et al. A multicenter, randomized, open-label, phase 2 clinical study of telitacicept in adult patients with generalized myasthenia gravis. Eur J Neurol. 2024;31(8):e16322. doi:10.1111/ene.16322
3. RemeGen announces exciting results of telitacicept phase 3 clinical trial for patients with generalized myasthenia gravis. News release. RemeGen Co, Ltd. April 8, 2025. Accessed September 28, 2026. https://www.prnewswire.com/news-releases/remegen-announces-exciting-results-of-telitacicept-phase-3-clinical-trial-for-patients-with-generalized-myasthenia-gravis-302424073.html
4. Telitacicept demonstrates sustained efficacy and favorable safety profile in 48-week China phase 3 open-label extension generalized myasthenia gravis data. News release. Vor Bio. October 29, 2025. Accessed September 28, 2026. https://ir.vorbio.com/news-releases/news-release-details/telitacicept-demonstrates-sustained-efficacy-and-favorable