Novel Synthetic Peptide Delays Disease Progression in Sub Class of Patients with Progressive Multiple Sclerosis: Presented at AAN
The investigational agent MBP8298, a synthetic peptide identical to a segment of human myelin basic protein, has been found safe and effective in a sub-group of multiple sclerosis (MS) patients with HLA DR2/DR4 haplotypes, according to results from a phase 2/3 double- blind placebo controlled trial. The study's authors explained that MBP8298 is a synthetic peptide that corresponds to residues 82-98 of human MBP, a sequence that is the immuno-dominant target of both B-cells and T-cells in MS patients with HLA haplotype DR2.
Previous studies have shown that intravenous administration of MBP8298 according to the principle of high dose tolerance induction resulted in long term suppression of anti-MBP autoantibody levels in cerebrospinal fluid of a large fraction of progressive MS patients.
"This study shows that an injection of 500 mg of MBP8298 is safe. Disease progression has been delayed in HLA class 2 patients," said Ingrid Catz, senior scientist, Multiple Sclerosis Patient Care and Research Clinic, Department of Medicine, University of Alberta, Edmonton, Canada, and co-inventor of MBP8298.
In their double-blind, placebo controlled trial, which was followed by an open label protocol, Dr. Catz and colleagues administered a 500-mg dose of MBP8298 or placebo once every 6 months for 2 years, with an indefinite follow-on treatment period for compassionate use. In total, 32 patients received treatment, 16 in the active treatment group, and 16 in the placebo arm. The two groups were matched for age, weight, gender, type of multiple sclerosis, disease duration, and Expanded Disability Status Scale. "We did clinical assessments twice at study entry, and every 6 months using independent neurologists.
Data are still being collected," Dr. Catz said. Contingency data at 24 months of study showed no significant difference between placebo and MBP8298. However, subset analysis by HLA-DR haplotype revealed a median time to disease progression in patients with a HLA-DR2 and/or HLA-DR4 haplotypes of 18 months in the placebo group, and 78 months in the active treatment arm, (P =.004).
"This shows that the median time to first confirmed disease progression was delayed by 60 months in the group of patients who received MBP8298, compared to the placebo group," Dr. Catz said. She noted that while levels of anti-MBP auto-antibodies found in the cerebral spinal fluid of many of the patients on active treatment were suppressed, antibody suppression did not predict clinical benefit.
No serious adverse events occurred on treatment. The most serious drug related events were mild and transient injection site reactions, she said. "We have a wealthy patient experience, with over 300 patient years, and 19 of the 32 patients remain on MBP8298 for compassionate use," Dr. Catz said.
"The identification of this responder group has enabled a more efficient design of a larger, confirmatory clinical trial of MBP8298, which is currently underway," Dr. Catz said. Financial support was provided by BioMS Medical Corp, Edmonton, Canada. [Presentation title: Intravenous Synthetic Peptide MBP8298 Significantly Delayed Disease Progression in an HLA Class II- Defined Cohort of Patients with Progressive Multiple Sclerosis. Abstract S12.004]