European Study: Mitoxantrone May Help Secondary-Progressive MS

September 11, 1998.

Summary: Preliminary results of a Phase 3 study of Novantrone (mitoxantrone HCl for injection) were presented at the 14th Congress of European Committee for Treatment and Research in Multiple Sclerosis in Stockholm on September 9-12, 1998. Results suggest:

This potent immune-suppressing drug may reduce relapses and slow disease progression in those with relapsing-remitting and secondary-progressive MS. Full data analysis has not yet been completed, and results have not yet been published to receive full scrutiny by the medical community. Concerns about significant long-term heart toxicity have been raised, and await further evaluation.

The Drug: Mitoxantrone is a potent immune-suppressing drug that kills B and T lymphocytes (immune cells). It has been shown to prevent the development of the MS-like disease EAE in rodents. In the U.S., the drug is currently approved as therapy for non-lymphocytic leukemia in adults. It is also approved for use in combination with corticosteroids as chemotherapy for patients with pain related to advanced prostate cancer. In other countries, mitoxantrone is approved for the treatment of non-Hodgkin's lymphoma, breast cancer and hepatoma. Mitoxantrone has been studied in MS in a number of smaller clinical trials in Europe and North America, with modest results and some safety concerns reported.

The Trial: This Phase 3 study involved 188 patients with relapsing-remitting or secondary-progressive MS. Patients received intravenous mitoxantrone every three months for up to two years, or an inactive placebo.

Results: Preliminary analysis of the results of the trial, performed by the drug company, suggests that mitoxantrone reduced the number of MS attacks and reduced the number of active MS lesions (damaged areas) apparent in MRI images enhanced with gadolinium. The drug also appears to slow the progression of disability. Full data have not yet been analyzed and have not yet been published for complete scrutiny, nor have they been submitted to any drug regulatory authority for consideration as an MS treatment.

Comments: These preliminary results suggest that mitoxantrone has potential as a treatment for relapsing-remitting and secondary-progressive MS. However, prior experience with mitoxantrone in persons with MS and other disorders indicates that extended use of the drug can lead to significant toxicity to the heart. It is unclear, therefore, how long this drug can be used without major complications. It is also unclear if mitoxantrone can be used safely and effectively in combination with, or in sequence with, other approved MS medications. Additional studies are needed to determine whether it is safe to use mitoxantrone in MS for periods longer than two years, and to determine if it can be used along with other MS treatments without increased side effects.

The National Multiple Sclerosis Society will track information about the potential use of mitoxantrone in MS. We urge rapid publication of relevant clinical data and a more complete assessment of the potential for long-term risk of this agent.

© 1998 The National Multiple Sclerosis Society