FDA Ruling on Mitoxantrone for Multiple Sclerosis

abstract & commentary

Source: Letter from the FDA, January 28, 2000.

On january 28, 2000, an fda advisory panel recommended the approval of mitoxantrone (Novantrone, Immunex Corp.) for progressive forms of multiple sclerosis (MS). The panel had reviewed data presented at meetings, but not yet published in full, of a phase III European trial comparing efficacy of two doses of mitoxantrone (5 and 12 mg/m2) to placebo in 188 patients with secondary progressive MS. The patient inclusion criteria required progression of at least 1 EDSS over the previous 18 months, with a baseline EDSS between 3 and 6.

Patients receiving mitoxantrone IV every three months for two years had significant improvement in EDSS and ambulation index. The annual relapse rate and time to first relapse also improved. The effect was more pronounced in the higher dose group. In addition, brain MRI evaluations in 110 patients at the high dose showed a significant (P < 0.05) reduction in new or enhancing lesions compared to placebo.

Common side effects included alopecia, nausea, urinary tract infections, and leukopenia, but reportedly no substantial cardiotoxicity occurred in this short-term use. Cardiotoxicity, unfortunately, is a well-recognized, cumulative dose-dependent effect of this potent drug in its standard use in acute nonlymphocytic leukemia, so additional long-term safety testing is required. Mitoxantrone may only provide short-term control of MS disease activity, and extended use of the drug will not be possible.


Mitoxantrone, therefore, is not likely to be a first-line therapy, but may be an option for patients for severe refractory disease that has not responded to conventional therapy such as interferon-beta. It is unclear if mitoxantrone can be used in combination with, or in sequence with, other approved MS drugs. Hopefully, with improved selective immunomodulatory therapies now in development (e.g., interleukin-12 antagonists), there will be less need for toxic immunosuppressive drug regimens. We await the full publication of the clinical data and a more complete assessment of long-term risks. Concurrent in time with the above FDA report, Biogen, Inc., on January 31, 2000, released via the public press and National Multiple Sclerosis Society that an independent data and safety monitoring committee determined that Avonex provided a statistically significant delay of onset of clinically definite MS compared with placebo. —bra


a. recently received an FDA advisory panel recommendation for treating progressive forms of MS.

b. may only provide short-term control of MS disease activity.

c. is not possible to use for extended periods.

d. needs a more complete assessment of long-term risks.

e. All of the above