Liposomal Mitoxantrone Shows Early Safety Signal in Phase 2 NMOSD Trial

A phase 2 trial found that liposomal mitoxantrone hydrochloride, an investigational reformulation of an older immunosuppressant, showed an acceptable safety profile and a potential trend toward fewer relapses in patients with neuromyelitis optica spectrum disorder (NMOSD). Investigators presented the findings at the 10th Joint ACTRIMS-ECTRIMS Meeting (MSToronto2026), held October 21-23, 2026, in Toronto, Ontario, Canada.¹

The trial was led by Junwei Hao and colleagues at Xuanwu Hospital, Capital Medical University, in Beijing, China, in collaboration with CSPC Pharmaceutical Group, which is developing the liposomal formulation. Conventional mitoxantrone, an anthracenedione chemotherapy drug, has been used as a second-line option in relapsing or highly active NMOSD, but its use is limited by cumulative, dose-dependent cardiotoxicity and a risk of treatment-related leukemia. Liposomal formulations are designed to reduce cardiac drug exposure while prolonging the drug's presence in immune-related tissue.^1,2

The multicenter, randomized, double-blind, placebo-controlled, parallel-group trial enrolled patients with NMOSD who had at least 1 relapse in the year before screening, or at least 2 relapses in the prior 2 years, and an Expanded Disability Status Scale (EDSS) score of 7.5 or lower. Participants were randomized 1:1:1 to 8 mg/m2 liposomal mitoxantrone, 12 mg/m2 liposomal mitoxantrone, or placebo, given intravenously on day 1 of each 12-week cycle for 5 cycles. The primary endpoint was time to first protocol-defined relapse within 48 weeks.

Of 46 patients enrolled across 7 centers in China, 15 received the 8 mg/m2 dose, 16 received the 12 mg/m2 dose, and 15 received placebo. Relative to placebo, the risk of relapse was reduced by 52.5% in the 8 mg/m2 group and by 11.7% in the 12 mg/m2 group. The least-squares mean change in EDSS from baseline to week 48 was -0.35 (95% CI, -0.91 to 0.21) with 8 mg/m2, -0.62 (95% CI, -1.15 to -0.09) with 12 mg/m2, and -0.19 (95% CI, -0.737 to 0.365) with placebo.¹

READ MORE: Divozilimab Cuts Relapse Risk at 1 Year in Phase 3 AQUARELLE Trial of NMOSD

All patients in both liposomal mitoxantrone groups experienced treatment-emergent adverse events (AEs), compared with 93.3% of the placebo group. Most AEs were grade 1 or 2 in severity; the incidence of grade 3 or higher events was 26.7% with 8 mg/m2, 18.8% with 12 mg/m2, and 40.0% with placebo. The investigators concluded that the safety profile at the doses tested was acceptable, with a potential trend toward relapse reduction.

Mitoxantrone was first approved by the FDA in 1996 for certain cancers and was expanded in October 2000 to cover worsening relapsing-remitting, secondary progressive, and progressive-relapsing multiple sclerosis, marketed as Novantrone. Its use in MS has since declined because of cardiotoxicity that can emerge during or years after treatment; the FDA label caps cumulative lifetime dosing at 140 mg/m2 and requires cardiac function monitoring before every dose.²

Mitoxantrone's use in NMOSD specifically emerged from observational experience rather than a dedicated regulatory approval. In a 2013 study of 51 patients with NMOSD treated with conventional mitoxantrone, the annualized relapse rate fell from 1.82 to 0.37 after 1 year of treatment, and mean EDSS improved by 1.3 points, though 1 patient developed acute myeloid leukemia after a mean of 4.8 years of exposure.³

Liposomal mitoxantrone, including the CSPC-developed formulation tested in this trial, is designed to encapsulate the drug to limit cardiac exposure while extending its activity in immune-related tissue. The formulation remains investigational and has not been approved for any indication.¹

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REFERENCES
1. Yang X, Li C, Zhang M, et al. Efficacy and safety of liposomal mitoxantrone hydrochloride in neuromyelitis optica spectrum disorder: a randomized, double-blind, placebo-controlled, parallel-group phase II trial. Abstract 1435. Presented at: 10th Joint ACTRIMS-ECTRIMS Meeting (MSToronto2026); October 21-23, 2026; Toronto, Ontario, Canada.
2. Mitoxantrone (marketed as Novantrone) information. FDA. Published July 29, 2008. Accessed October 21, 2026. https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm126445.htm
3. Cabre P, Olindo S, Marignier R, Jeannin S, Merle H, Smadja D, for the French National Observatory of Multiple Sclerosis. Efficacy of mitoxantrone in neuromyelitis optica spectrum: clinical and neuroradiological study. J Neurol Neurosurg Psychiatry. 2013;84(5):511-516. doi:10.1136/jnnp-2012-303121