A to Z of MS Dirucotide (MBP8298)

Dirucotide (MBP8298) was an experimental drug that was tested in a phase II trial for relapsing remitting multiple sclerosis and three phase III trials for secondary progressive MS.

In July 2009, after evaluating data from clinical trials, Eli Lilly and BioMS Medical, the companies developing dirucotide, decided to end all further studies.

How dirucotide works

Myelin basic protein (MBP) is believed to be important in the process of myelnation of nerves in the brain and spinal cord. Dirucotide is a copy of part of MBP and was thought to act by causing or restoring tolerance to immune attack at this section of MBP.

How is dirucotide given?

Dirucotide was given by intravenous infusion.

Clinical studies

Secondary progressive MS
In a phase II clinical trial, 32 people with progressive MS received an infusion of MBP8298 every six months for 24 months. No significant difference was found between MBP8298 and placebo treatment. However, a statistically significant delay in clinical progression was found in people with certain genetically determined HLA types.

HLA are genes located on cells in the body that help the immune system distinguish between foreign invaders and the body's own tissue. In MS, this distinction doesn't occur and the immune system attacks myelin, the fatty protein that covers nerve axons in the central nervous system, as if it were foreign. In people with certain HLA types (65-75% of all people with MS), MBP8298 treatment resulted in a delay in progression of MS (78 months for dirucotide versus 18 months for placebo).

However, in a phase III study in secondary progressive MS (MAESTRO-01) dirucotide failed to meet its primary endpoint of delaying disease progression, as measured by the Expanded Disability Status Scale (EDSS). There were also no statistically significant differences between dirucotide and placebo on the secondary endpoints of the study.

Following the announcement of these results, two ongoing trials of MBP8298 in secondary progressive MS (MAESTRO-02 and MAESTRO-03) were discontinued.

Relapsing remitting MS
In a phase II clinical trial (MINDSET-01) in people with relapsing remitting MS, dirucotide also failed to meet its primary endpoint on annualised relapse rate and associated secondary MRI endpoints.

References

Warren KG, et al.
Intravenous synthetic peptide MBP8298 delayed disease progression in an HLA Class II-defined cohort of patients with progressive multiple sclerosis: results of a 24-month double-blind placebo-controlled clinical trial and 5 years of follow-up treatment.
European Journal of Neurology 2006; 13(8): 887-895.
abstract

Dirucotide does not meet primary endpoint in phase III MAESTRO-01 trial in secondary progressive multiple sclerosis.
BioMS press release - 29 July 2009.
read online

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